WO2013045600A1 - Novel peptide derivatives as antibiotics - Google Patents
Novel peptide derivatives as antibiotics Download PDFInfo
- Publication number
- WO2013045600A1 WO2013045600A1 PCT/EP2012/069166 EP2012069166W WO2013045600A1 WO 2013045600 A1 WO2013045600 A1 WO 2013045600A1 EP 2012069166 W EP2012069166 W EP 2012069166W WO 2013045600 A1 WO2013045600 A1 WO 2013045600A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- xaa
- compound
- lysine
- formula
- hydroxylysine
- Prior art date
Links
- 239000003242 anti bacterial agent Substances 0.000 title description 11
- 229940088710 antibiotic agent Drugs 0.000 title description 10
- 108090000765 processed proteins & peptides Proteins 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 170
- 230000003115 biocidal effect Effects 0.000 claims abstract description 53
- 239000000203 mixture Substances 0.000 claims abstract description 44
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 63
- 239000004472 Lysine Substances 0.000 claims description 58
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 54
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 42
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 claims description 39
- 229940117976 5-hydroxylysine Drugs 0.000 claims description 38
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 claims description 38
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 29
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims description 29
- 229960003104 ornithine Drugs 0.000 claims description 29
- ACWKOLUJJZRCNF-UHFFFAOYSA-N 2,4-diamino-3-hydroxybutanoic acid Chemical compound NCC(O)C(N)C(O)=O ACWKOLUJJZRCNF-UHFFFAOYSA-N 0.000 claims description 27
- 241000607735 Xenorhabdus nematophila Species 0.000 claims description 27
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 26
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 26
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 26
- 239000003937 drug carrier Substances 0.000 claims description 19
- 239000004471 Glycine Substances 0.000 claims description 16
- 239000012228 culture supernatant Substances 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 229960000318 kanamycin Drugs 0.000 claims description 14
- 229930027917 kanamycin Natural products 0.000 claims description 14
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 claims description 14
- 229930182823 kanamycin A Natural products 0.000 claims description 14
- 239000004475 Arginine Substances 0.000 claims description 11
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- OGNSCSPNOLGXSM-UHFFFAOYSA-N 2,4-diaminobutyric acid Chemical compound NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 claims description 10
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 claims description 10
- 229930182566 Gentamicin Natural products 0.000 claims description 10
- IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 claims description 10
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 10
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims description 10
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 10
- 229960002518 gentamicin Drugs 0.000 claims description 10
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 claims description 8
- 239000001963 growth medium Substances 0.000 claims description 8
- 238000009630 liquid culture Methods 0.000 claims description 7
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 6
- BJBUEDPLEOHJGE-UHFFFAOYSA-N (2R,3S)-3-Hydroxy-2-pyrolidinecarboxylic acid Natural products OC1CCNC1C(O)=O BJBUEDPLEOHJGE-UHFFFAOYSA-N 0.000 claims description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 5
- SEAQXRCXGIJOET-ONQHYROSSA-N (2s)-2,5-diamino-3,4-dihydroxypentanoic acid Chemical compound NCC(O)C(O)[C@H](N)C(O)=O SEAQXRCXGIJOET-ONQHYROSSA-N 0.000 claims description 5
- ZVDGZUVHJGGWSG-BKLSDQPFSA-N (2s)-2,5-diamino-4-hydroxypentanoic acid Chemical compound NCC(O)C[C@H](N)C(O)=O ZVDGZUVHJGGWSG-BKLSDQPFSA-N 0.000 claims description 5
- ALWBRQWTMGZSIM-QHWRUIEBSA-N (2s)-2,6-diamino-3,4-dihydroxyhexanoic acid Chemical compound NCCC(O)C(O)[C@H](N)C(O)=O ALWBRQWTMGZSIM-QHWRUIEBSA-N 0.000 claims description 5
- DXLAWQDSGXTFFD-YCXLAJEKSA-N (2s)-2,6-diamino-3,5-dihydroxyhexanoic acid Chemical compound NCC(O)CC(O)[C@H](N)C(O)=O DXLAWQDSGXTFFD-YCXLAJEKSA-N 0.000 claims description 5
- WIMASFVWEOESGF-KLFYCJEISA-N (2s)-2,6-diamino-4,5-dihydroxyhexanoic acid Chemical compound NCC(O)C(O)C[C@H](N)C(O)=O WIMASFVWEOESGF-KLFYCJEISA-N 0.000 claims description 5
- SHINASQYHDCLEU-BKLSDQPFSA-N (2s)-4-aminopyrrolidine-2-carboxylic acid Chemical compound NC1CN[C@H](C(O)=O)C1 SHINASQYHDCLEU-BKLSDQPFSA-N 0.000 claims description 5
- ZIWHMENIDGOELV-BKLSDQPFSA-N (2s)-4-fluoropyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CC(F)CN1 ZIWHMENIDGOELV-BKLSDQPFSA-N 0.000 claims description 5
- UHPDQDWXMXBLRX-IMJSIDKUSA-N (3S)-3-hydroxy-L-ornithine Chemical compound NCC[C@H](O)[C@H](N)C(O)=O UHPDQDWXMXBLRX-IMJSIDKUSA-N 0.000 claims description 5
- XFZIPCXDWCWTCH-VKHMYHEASA-N (4s)-1,3-oxazolidin-3-ium-4-carboxylate Chemical compound OC(=O)[C@@H]1COCN1 XFZIPCXDWCWTCH-VKHMYHEASA-N 0.000 claims description 5
- OMGHIGVFLOPEHJ-UHFFFAOYSA-N 2,5-dihydro-1h-pyrrol-1-ium-2-carboxylate Chemical compound OC(=O)C1NCC=C1 OMGHIGVFLOPEHJ-UHFFFAOYSA-N 0.000 claims description 5
- YSVMULOOWPBERR-UHFFFAOYSA-N 3-hydroxylysine Chemical compound NCCCC(O)C(N)C(O)=O YSVMULOOWPBERR-UHFFFAOYSA-N 0.000 claims description 5
- ASYBZHICIMVQII-UHFFFAOYSA-N 4-hydroxylysine Chemical compound NCCC(O)CC(N)C(O)=O ASYBZHICIMVQII-UHFFFAOYSA-N 0.000 claims description 5
- IADUEWIQBXOCDZ-VKHMYHEASA-N Azetidine-2-carboxylic acid Natural products OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 claims description 5
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims description 5
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 5
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 5
- FSBIGDSBMBYOPN-VKHMYHEASA-N L-canavanine Chemical compound OC(=O)[C@@H](N)CCONC(N)=N FSBIGDSBMBYOPN-VKHMYHEASA-N 0.000 claims description 5
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 claims description 5
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 5
- HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 claims description 5
- ULSZVNJBVJWEJE-VKHMYHEASA-N L-thiazolidine-2-carboxylic acid zwitterion Chemical compound [O-]C(=O)[C@H]1[NH2+]CCS1 ULSZVNJBVJWEJE-VKHMYHEASA-N 0.000 claims description 5
- DZLNHFMRPBPULJ-VKHMYHEASA-N L-thioproline Chemical compound OC(=O)[C@@H]1CSCN1 DZLNHFMRPBPULJ-VKHMYHEASA-N 0.000 claims description 5
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 claims description 5
- FSBIGDSBMBYOPN-UHFFFAOYSA-N O-guanidino-DL-homoserine Natural products OC(=O)C(N)CCON=C(N)N FSBIGDSBMBYOPN-UHFFFAOYSA-N 0.000 claims description 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 5
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 5
- 239000004473 Threonine Substances 0.000 claims description 5
- 229940126574 aminoglycoside antibiotic Drugs 0.000 claims description 5
- WBGBOXYJYPVLQJ-UHFFFAOYSA-N aziridine-2-carboxylic acid Chemical compound OC(=O)C1CN1 WBGBOXYJYPVLQJ-UHFFFAOYSA-N 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 229960002173 citrulline Drugs 0.000 claims description 5
- 235000013477 citrulline Nutrition 0.000 claims description 5
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 5
- 229960002591 hydroxyproline Drugs 0.000 claims description 5
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 claims description 5
- BJBUEDPLEOHJGE-IMJSIDKUSA-N trans-3-hydroxy-L-proline Chemical compound O[C@H]1CC[NH2+][C@@H]1C([O-])=O BJBUEDPLEOHJGE-IMJSIDKUSA-N 0.000 claims description 5
- LWGJTAZLEJHCPA-UHFFFAOYSA-N n-(2-chloroethyl)-n-nitrosomorpholine-4-carboxamide Chemical compound ClCCN(N=O)C(=O)N1CCOCC1 LWGJTAZLEJHCPA-UHFFFAOYSA-N 0.000 claims 3
- 238000000034 method Methods 0.000 abstract description 44
- 238000011282 treatment Methods 0.000 abstract description 41
- 208000035143 Bacterial infection Diseases 0.000 description 33
- 208000022362 bacterial infectious disease Diseases 0.000 description 33
- 230000000844 anti-bacterial effect Effects 0.000 description 28
- 208000015181 infectious disease Diseases 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 19
- 230000001580 bacterial effect Effects 0.000 description 17
- 241000894006 Bacteria Species 0.000 description 15
- 201000010099 disease Diseases 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 241000282414 Homo sapiens Species 0.000 description 13
- 229910001868 water Inorganic materials 0.000 description 13
- 230000000845 anti-microbial effect Effects 0.000 description 12
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- -1 cefepim Chemical compound 0.000 description 10
- 241000588724 Escherichia coli Species 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 108010059993 Vancomycin Proteins 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 239000002054 inoculum Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 229960003165 vancomycin Drugs 0.000 description 9
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 9
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 9
- 239000003643 water by type Substances 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 230000000813 microbial effect Effects 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 235000002639 sodium chloride Nutrition 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- 235000014469 Bacillus subtilis Nutrition 0.000 description 7
- 241000191967 Staphylococcus aureus Species 0.000 description 7
- 241000191963 Staphylococcus epidermidis Species 0.000 description 7
- 241000122973 Stenotrophomonas maltophilia Species 0.000 description 7
- 239000003085 diluting agent Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 230000002265 prevention Effects 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 241000588655 Moraxella catarrhalis Species 0.000 description 6
- 239000004599 antimicrobial Substances 0.000 description 6
- 229960003405 ciprofloxacin Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000006062 fragmentation reaction Methods 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 238000004949 mass spectrometry Methods 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 230000001629 suppression Effects 0.000 description 6
- 241000588626 Acinetobacter baumannii Species 0.000 description 5
- 244000063299 Bacillus subtilis Species 0.000 description 5
- 241000588697 Enterobacter cloacae Species 0.000 description 5
- 241000194032 Enterococcus faecalis Species 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 241000588749 Klebsiella oxytoca Species 0.000 description 5
- 241000588747 Klebsiella pneumoniae Species 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 241000282898 Sus scrofa Species 0.000 description 5
- 239000004098 Tetracycline Substances 0.000 description 5
- 229960000723 ampicillin Drugs 0.000 description 5
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 229960001225 rifampicin Drugs 0.000 description 5
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 229960002180 tetracycline Drugs 0.000 description 5
- 229930101283 tetracycline Natural products 0.000 description 5
- 235000019364 tetracycline Nutrition 0.000 description 5
- 150000003522 tetracyclines Chemical class 0.000 description 5
- 241000283690 Bos taurus Species 0.000 description 4
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 4
- 239000006391 Luria-Bertani Medium Substances 0.000 description 4
- 241000589516 Pseudomonas Species 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000005277 cation exchange chromatography Methods 0.000 description 4
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 229960003907 linezolid Drugs 0.000 description 4
- TYZROVQLWOKYKF-ZDUSSCGKSA-N linezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCOCC1 TYZROVQLWOKYKF-ZDUSSCGKSA-N 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 238000005016 nuclear Overhauser enhanced spectroscopy Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000009044 synergistic interaction Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 241000271566 Aves Species 0.000 description 3
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 3
- 241000588914 Enterobacter Species 0.000 description 3
- 241000194031 Enterococcus faecium Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 201000008225 Klebsiella pneumonia Diseases 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241001293418 Mannheimia haemolytica Species 0.000 description 3
- 241000606856 Pasteurella multocida Species 0.000 description 3
- 206010035717 Pneumonia klebsiella Diseases 0.000 description 3
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 3
- 241000607720 Serratia Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 241000193996 Streptococcus pyogenes Species 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 244000052616 bacterial pathogen Species 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 229960003324 clavulanic acid Drugs 0.000 description 3
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 238000013467 fragmentation Methods 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 229960000707 tobramycin Drugs 0.000 description 3
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- 238000001551 total correlation spectroscopy Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- LITBAYYWXZOHAW-XDZRHBBOSA-N (2s,5r,6r)-6-[[(2r)-2-[(4-ethyl-2,3-dioxopiperazine-1-carbonyl)amino]-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;(2s,3s,5r)-3-methyl-4,4,7-trioxo-3-(triazol-1-ylmethyl)-4$l^{6}-thia-1-azabicyclo[3.2.0]hept Chemical compound C([C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C(O)=O)(=O)=O)N1C=CN=N1.O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 LITBAYYWXZOHAW-XDZRHBBOSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 2
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 2
- 238000003979 3D HSQC-TOCSY Methods 0.000 description 2
- ZPLCXHWYPWVJDL-UHFFFAOYSA-N 4-[(4-hydroxyphenyl)methyl]-1,3-oxazolidin-2-one Chemical compound C1=CC(O)=CC=C1CC1NC(=O)OC1 ZPLCXHWYPWVJDL-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 241000589291 Acinetobacter Species 0.000 description 2
- 244000034356 Aframomum angustifolium Species 0.000 description 2
- WZPBZJONDBGPKJ-UHFFFAOYSA-N Antibiotic SQ 26917 Natural products O=C1N(S(O)(=O)=O)C(C)C1NC(=O)C(=NOC(C)(C)C(O)=O)C1=CSC(N)=N1 WZPBZJONDBGPKJ-UHFFFAOYSA-N 0.000 description 2
- 241000606124 Bacteroides fragilis Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000589513 Burkholderia cepacia Species 0.000 description 2
- 241000606161 Chlamydia Species 0.000 description 2
- 108010013198 Daptomycin Proteins 0.000 description 2
- 108090000204 Dipeptidase 1 Proteins 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 241000192125 Firmicutes Species 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 241000606790 Haemophilus Species 0.000 description 2
- 241000606768 Haemophilus influenzae Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000006142 Luria-Bertani Agar Substances 0.000 description 2
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 2
- 206010029803 Nosocomial infection Diseases 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 229960003644 aztreonam Drugs 0.000 description 2
- WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 2
- 102000006635 beta-lactamase Human genes 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 229960002227 clindamycin Drugs 0.000 description 2
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- DOAKLVKFURWEDJ-QCMAZARJSA-N daptomycin Chemical compound C([C@H]1C(=O)O[C@H](C)[C@@H](C(NCC(=O)N[C@@H](CCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@H](CO)C(=O)N[C@H](C(=O)N1)[C@H](C)CC(O)=O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CCCCCCCCC)C(=O)C1=CC=CC=C1N DOAKLVKFURWEDJ-QCMAZARJSA-N 0.000 description 2
- 229960005484 daptomycin Drugs 0.000 description 2
- 238000012581 double quantum filtered COSY Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 229940032049 enterococcus faecalis Drugs 0.000 description 2
- 229960003276 erythromycin Drugs 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 229960002182 imipenem Drugs 0.000 description 2
- ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229960003085 meticillin Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000006916 nutrient agar Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- UWYHMGVUTGAWSP-JKIFEVAISA-N oxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1 UWYHMGVUTGAWSP-JKIFEVAISA-N 0.000 description 2
- 229960001019 oxacillin Drugs 0.000 description 2
- 229940104641 piperacillin / tazobactam Drugs 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- DWHGNUUWCJZQHO-ZVDZYBSKSA-M potassium;(2s,5r,6r)-6-[[(2r)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;(2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [K+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21.C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 DWHGNUUWCJZQHO-ZVDZYBSKSA-M 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- XUSXOPRDIDWMFO-CTMSJIKGSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[[(2s,3r)-3-amino-6-[(1s)-1-aminoethyl]-3,4-dihydro-2h-pyran-2-yl]oxy]-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC=C(O2)[C@H](C)N)N)[C@@H](N)C[C@H]1N XUSXOPRDIDWMFO-CTMSJIKGSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- VCOPTHOUUNAYKQ-WBTCAYNUSA-N (3s)-3,6-diamino-n-[[(2s,5s,8e,11s,15s)-15-amino-11-[(6r)-2-amino-1,4,5,6-tetrahydropyrimidin-6-yl]-8-[(carbamoylamino)methylidene]-2-(hydroxymethyl)-3,6,9,12,16-pentaoxo-1,4,7,10,13-pentazacyclohexadec-5-yl]methyl]hexanamide;(3s)-3,6-diamino-n-[[(2s,5s,8 Chemical compound N1C(=O)\C(=C/NC(N)=O)NC(=O)[C@H](CNC(=O)C[C@@H](N)CCCN)NC(=O)[C@H](C)NC(=O)[C@@H](N)CNC(=O)[C@@H]1[C@@H]1NC(N)=NCC1.N1C(=O)\C(=C/NC(N)=O)NC(=O)[C@H](CNC(=O)C[C@@H](N)CCCN)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CNC(=O)[C@@H]1[C@@H]1NC(N)=NCC1 VCOPTHOUUNAYKQ-WBTCAYNUSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 238000004701 1H-13C HSQC Methods 0.000 description 1
- AWBXTNNIECFIHT-XZQQZIICSA-N 2-[(1r,2r,3s,4r,5r,6s)-3-(diaminomethylideneamino)-4-[(2r,3r,4r,5s)-3-[(2s,3s,4s,5r,6s)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine;2-[(1r,2r,3s,4r,5r,6s)-3-( Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](CO)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O AWBXTNNIECFIHT-XZQQZIICSA-N 0.000 description 1
- APRZHQXAAWPYHS-UHFFFAOYSA-N 4-[5-[3-(carboxymethoxy)phenyl]-3-(4,5-dimethyl-1,3-thiazol-2-yl)tetrazol-3-ium-2-yl]benzenesulfonate Chemical compound S1C(C)=C(C)N=C1[N+]1=NC(C=2C=C(OCC(O)=O)C=CC=2)=NN1C1=CC=C(S([O-])(=O)=O)C=C1 APRZHQXAAWPYHS-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 241000590020 Achromobacter Species 0.000 description 1
- 208000020154 Acnes Diseases 0.000 description 1
- 241000606750 Actinobacillus Species 0.000 description 1
- 241000186046 Actinomyces Species 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241000607534 Aeromonas Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 241000606646 Anaplasma Species 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- 108010023063 Bacto-peptone Proteins 0.000 description 1
- 241000606660 Bartonella Species 0.000 description 1
- 241000604933 Bdellovibrio Species 0.000 description 1
- 241000186000 Bifidobacterium Species 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 241000588807 Bordetella Species 0.000 description 1
- 241000589968 Borrelia Species 0.000 description 1
- 241000589562 Brucella Species 0.000 description 1
- 241001453380 Burkholderia Species 0.000 description 1
- 101100424627 Caenorhabditis elegans mec-12 gene Proteins 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- 241000190890 Capnocytophaga Species 0.000 description 1
- 108010065839 Capreomycin Proteins 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000207206 Cardiobacterium Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000588881 Chromobacterium Species 0.000 description 1
- 241000588923 Citrobacter Species 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241001445332 Coxiella <snail> Species 0.000 description 1
- 241000186427 Cutibacterium acnes Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- ASXBYYWOLISCLQ-UHFFFAOYSA-N Dihydrostreptomycin Natural products O1C(CO)C(O)C(O)C(NC)C1OC1C(CO)(O)C(C)OC1OC1C(N=C(N)N)C(O)C(N=C(N)N)C(O)C1O ASXBYYWOLISCLQ-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 239000004129 EU approved improving agent Substances 0.000 description 1
- 241000605314 Ehrlichia Species 0.000 description 1
- 241000194033 Enterococcus Species 0.000 description 1
- 241000186811 Erysipelothrix Species 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 241000589601 Francisella Species 0.000 description 1
- 241000605909 Fusobacterium Species 0.000 description 1
- DNYGXMICFMACRA-XHEDQWPISA-N Gentamicin C2b Chemical compound O1[C@H](CNC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N DNYGXMICFMACRA-XHEDQWPISA-N 0.000 description 1
- 241000589989 Helicobacter Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 241001056120 Klebsiella pneumoniae ATCC 43816 Species 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 241000589902 Leptospira Species 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 241001293415 Mannheimia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000191938 Micrococcus luteus Species 0.000 description 1
- 241000588621 Moraxella Species 0.000 description 1
- 241000588771 Morganella <proteobacterium> Species 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241001468109 Neorickettsia Species 0.000 description 1
- 241000187654 Nocardia Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241000606860 Pasteurella Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241000191992 Peptostreptococcus Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 241001148062 Photorhabdus Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010040201 Polymyxins Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000605894 Porphyromonas Species 0.000 description 1
- 241000605861 Prevotella Species 0.000 description 1
- 241000186429 Propionibacterium Species 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 239000005700 Putrescine Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- URWAJWIAIPFPJE-UHFFFAOYSA-N Rickamicin Natural products O1CC(O)(C)C(NC)C(O)C1OC1C(O)C(OC2C(CC=C(CN)O2)N)C(N)CC1N URWAJWIAIPFPJE-UHFFFAOYSA-N 0.000 description 1
- 241000606701 Rickettsia Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 229930192786 Sisomicin Natural products 0.000 description 1
- 241000123534 Sphaerophorus Species 0.000 description 1
- 241000605008 Spirillum Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000122971 Stenotrophomonas Species 0.000 description 1
- 241001478878 Streptobacillus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 201000005010 Streptococcus pneumonia Diseases 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241000589886 Treponema Species 0.000 description 1
- 241000203807 Tropheryma Species 0.000 description 1
- 241000202898 Ureaplasma Species 0.000 description 1
- XUSXOPRDIDWMFO-UHFFFAOYSA-N Verdamicin Natural products O1CC(O)(C)C(NC)C(O)C1OC1C(O)C(OC2C(CC=C(O2)C(C)N)N)C(N)CC1N XUSXOPRDIDWMFO-UHFFFAOYSA-N 0.000 description 1
- 241000607598 Vibrio Species 0.000 description 1
- 241000607757 Xenorhabdus Species 0.000 description 1
- 241000607734 Yersinia <bacteria> Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- PMZXXNPJQYDFJX-UHFFFAOYSA-N acetonitrile;2,2,2-trifluoroacetic acid Chemical compound CC#N.OC(=O)C(F)(F)F PMZXXNPJQYDFJX-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 229960004821 amikacin Drugs 0.000 description 1
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229950006334 apramycin Drugs 0.000 description 1
- XZNUGFQTQHRASN-XQENGBIVSA-N apramycin Chemical compound O([C@H]1O[C@@H]2[C@H](O)[C@@H]([C@H](O[C@H]2C[C@H]1N)O[C@@H]1[C@@H]([C@@H](O)[C@H](N)[C@@H](CO)O1)O)NC)[C@@H]1[C@@H](N)C[C@@H](N)[C@H](O)[C@H]1O XZNUGFQTQHRASN-XQENGBIVSA-N 0.000 description 1
- 229960005397 arbekacin Drugs 0.000 description 1
- MKKYBZZTJQGVCD-XTCKQBCOSA-N arbekacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)CC[C@H]1N MKKYBZZTJQGVCD-XTCKQBCOSA-N 0.000 description 1
- 229950004074 astromicin Drugs 0.000 description 1
- BIDUPMYXGFNAEJ-APGVDKLISA-N astromicin Chemical compound O[C@@H]1[C@H](N(C)C(=O)CN)[C@@H](OC)[C@@H](O)[C@H](N)[C@H]1O[C@@H]1[C@H](N)CC[C@@H]([C@H](C)N)O1 BIDUPMYXGFNAEJ-APGVDKLISA-N 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 229960001192 bekanamycin Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 229960004602 capreomycin Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 238000005100 correlation spectroscopy Methods 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 229960003807 dibekacin Drugs 0.000 description 1
- JJCQSGDBDPYCEO-XVZSLQNASA-N dibekacin Chemical compound O1[C@H](CN)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N JJCQSGDBDPYCEO-XVZSLQNASA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229960002222 dihydrostreptomycin Drugs 0.000 description 1
- ASXBYYWOLISCLQ-HZYVHMACSA-N dihydrostreptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](CO)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O ASXBYYWOLISCLQ-HZYVHMACSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 229950002339 elsamitrucin Drugs 0.000 description 1
- MGQRRMONVLMKJL-KWJIQSIXSA-N elsamitrucin Chemical compound O1[C@H](C)[C@H](O)[C@H](OC)[C@@H](N)[C@H]1O[C@@H]1[C@](O)(C)[C@@H](O)[C@@H](C)O[C@H]1OC1=CC=CC2=C(O)C(C(O3)=O)=C4C5=C3C=CC(C)=C5C(=O)OC4=C12 MGQRRMONVLMKJL-KWJIQSIXSA-N 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Natural products O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 1
- DNYGXMICFMACRA-UHFFFAOYSA-N gentamicin C1A Natural products O1C(CNC)CCC(N)C1OC1C(O)C(OC2C(C(NC)C(C)(O)CO2)O)C(N)CC1N DNYGXMICFMACRA-UHFFFAOYSA-N 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 244000000058 gram-negative pathogen Species 0.000 description 1
- 244000000059 gram-positive pathogen Species 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 1
- 238000000990 heteronuclear single quantum coherence spectrum Methods 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
- 229940097277 hygromycin b Drugs 0.000 description 1
- CFUQBFQTFMOZBK-QUCCMNQESA-N ibazocine Chemical compound C12=CC(O)=CC=C2C[C@H]2N(CC=C(C)C)CC[C@]1(C)C2(C)C CFUQBFQTFMOZBK-QUCCMNQESA-N 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960000798 isepamicin Drugs 0.000 description 1
- UDIIBEDMEYAVNG-ZKFPOVNWSA-N isepamicin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)O)[C@@H](N)C[C@H]1NC(=O)[C@@H](O)CN UDIIBEDMEYAVNG-ZKFPOVNWSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229930182824 kanamycin B Natural products 0.000 description 1
- SKKLOUVUUNMCJE-FQSMHNGLSA-N kanamycin B Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SKKLOUVUUNMCJE-FQSMHNGLSA-N 0.000 description 1
- SKKLOUVUUNMCJE-UHFFFAOYSA-N kanendomycin Natural products NC1C(O)C(O)C(CN)OC1OC1C(O)C(OC2C(C(N)C(O)C(CO)O2)O)C(N)CC1N SKKLOUVUUNMCJE-UHFFFAOYSA-N 0.000 description 1
- PVTHJAPFENJVNC-MHRBZPPQSA-N kasugamycin Chemical compound N[C@H]1C[C@H](NC(=N)C(O)=O)[C@@H](C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H]1O PVTHJAPFENJVNC-MHRBZPPQSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 238000000464 low-speed centrifugation Methods 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960004744 micronomicin Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 229960000808 netilmicin Drugs 0.000 description 1
- ZBGPYVZLYBDXKO-HILBYHGXSA-N netilmycin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@]([C@H](NC)[C@@H](O)CO1)(C)O)NCC)[C@H]1OC(CN)=CC[C@H]1N ZBGPYVZLYBDXKO-HILBYHGXSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229960005065 paromomycin sulfate Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 229940051027 pasteurella multocida Drugs 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229960003485 ribostamycin Drugs 0.000 description 1
- NSKGQURZWSPSBC-NLZFXWNVSA-N ribostamycin Chemical compound N[C@H]1[C@H](O)[C@@H](O)[C@H](CN)O[C@@H]1O[C@@H]1[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@H](CO)O2)O)[C@H](O)[C@@H](N)C[C@H]1N NSKGQURZWSPSBC-NLZFXWNVSA-N 0.000 description 1
- 229930190553 ribostamycin Natural products 0.000 description 1
- NSKGQURZWSPSBC-UHFFFAOYSA-N ribostamycin A Natural products NC1C(O)C(O)C(CN)OC1OC1C(OC2C(C(O)C(CO)O2)O)C(O)C(N)CC1N NSKGQURZWSPSBC-UHFFFAOYSA-N 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000007259 schaedler broth Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229960005456 sisomicin Drugs 0.000 description 1
- URWAJWIAIPFPJE-YFMIWBNJSA-N sisomycin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC=C(CN)O2)N)[C@@H](N)C[C@H]1N URWAJWIAIPFPJE-YFMIWBNJSA-N 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- UCPZQMVAIXQCSS-UHFFFAOYSA-M sodium 3,3-dimethyl-1-sulfonatosilylbutane Chemical compound [Na+].CC(C)(C)CC[SiH2]S([O-])(=O)=O UCPZQMVAIXQCSS-UHFFFAOYSA-M 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000004052 statestime proportional phase incrementation Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229940057056 streptoduocin Drugs 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- LPQZKKCYTLCDGQ-WEDXCCLWSA-N tazobactam Chemical compound C([C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C(O)=O)(=O)=O)N1C=CN=N1 LPQZKKCYTLCDGQ-WEDXCCLWSA-N 0.000 description 1
- 229960003865 tazobactam Drugs 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000001363 water suppression through gradient tailored excitation Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
Definitions
- Xaai is lysine; Xaa 2 and Xaa 3 are each 3-hydroxy-2,4- diaminobutanoic acid; Xaa 4 is glycine; Xaa 5 is ornithine; Xaa 6 is proline; Xaa 7 is histidine; Xaagis lysine or 5-hydroxylysine; Xaa 9 is 2,3-dehydroarginine; Xaagis lysine or 5-hydroxylysine; n is 4; and R is NH 2 .
- FIG. 4 shows bactericidal effects of Odilomycin A on growing P. aeruginosa
- the present invention comprises methods of treatment, suppression and/or prevention of bacterial infection comprising administration of extracts from Xenorhabdus nematophila strain CNCM 1-4530.
- Xenorhabdus nematophila strain CNCM 1-4530 culture supernatant from this strain and cell extracts derived from this strain exhibit antibiotic activity against Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Klebsiella pneumonia, Klebsiella oxytoca, Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Moraxella catarrhalis, Pseudomonas aeruginos and Stenotrophomonas maltophilia.
- n 4.
- one or more of Xaai, Xaa 2; Xaa 3 , Xaa , Xaa 5 , Xaa 6 , Xaa 7 , Xaa 8 , and Xaa ⁇ have the "D" configuration at the ⁇ -carbon of the amino acid residue.
- the configuration at the hydroxyl groups in the amino acid side chains may be "R” or "S", and may be independent of the configurations of other hydroxyl groups in the compounds of formula (I).
- one or more hydroxyl groups have the "R” configuration.
- one or more hydroxyl groups have the "S” configuration.
- each of the hydroxyl groups have the "R” configuration.
- each of the hydroxyl groups have the "S” configuration.
- compositions or methods may further comprise one or more additional antibacterial or antibiotic compounds in combination with a compound of formula (I) alone.
- additional antibacterial or antibiotic compounds include, but are not limited to, daptomycin, oxacillin, piperacillin/tazobactam, ticaricillin/clavulanic acid, amoxicillin/clavulanic acid, erythromycin, cefepim, clindamycin, imipenem, gentamicin, ciprofloxacin, aztreonam, vancomycin, linezolid, rifampicin, kanamycin, ampicillin, tetracycline, and the like.
- Another aspect of the present invention is a pharmaceutical composition comprising an effective amount of a compound of formula (I).
- Xaai is lysine.
- Xaa 5 is ornithine.
- n 4.
- the compound and/or composition is administered orally. In some embodiments, the compound and/or composition is administered subcutaneous ly. In some embodiments, the compound and/or composition is administered intravenously. In some embodiments, the compound and/or composition is administered intramuscularly. In some embodiments, the compound and/or composition is administered topically. In some embodiments, the compound and/or composition is administered parenterally.
- Odilomycin A was tested for antimicrobial activity against a wide range of bacteria involved in nosocomial and animal infection. It owns a wide spectrum of antibacterial activity against Gram-positive and Gram-negative pathogens (Table 8). With respect to Gram-positive bacteria, the antibacterial activities of Odilomycin A are strong, with MICs inferior to 1 ⁇ g/mL against S. aureus, S. epidermidis, and B. subtilis strains, including against some multiresistant clinical isolates (Table 9). Weak or no antibacterial activity was observed against E. faecalis, E. faecium, S. pneumoniae, and S. pyogenes.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14/342,446 US9260481B2 (en) | 2011-09-28 | 2012-09-28 | Peptide derivatives as antibiotics |
| EP12778971.7A EP2760881B1 (en) | 2011-09-28 | 2012-09-28 | Novel peptide derivatives as antibiotics |
| ES12778971.7T ES2657930T3 (es) | 2011-09-28 | 2012-09-28 | Nuevos derivados de péptidos como antibióticos |
| RU2014114996/04A RU2014114996A (ru) | 2011-09-28 | 2012-09-28 | Новые пептидные производные в качестве антибиотиков |
| CA2845735A CA2845735A1 (en) | 2011-09-28 | 2012-09-28 | Novel peptide derivatives as antibiotics |
| IN3010DEN2014 IN2014DN03010A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2011-09-28 | 2012-09-28 | |
| JP2014532400A JP6158188B2 (ja) | 2011-09-28 | 2012-09-28 | 抗生物質としての新規なペプチド誘導体 |
| CN201280046610.4A CN103827138B (zh) | 2011-09-28 | 2012-09-28 | 新的作为抗生素的肽衍生物 |
| IL231664A IL231664A0 (en) | 2011-09-28 | 2014-03-23 | Novel peptide histories as antibiotics |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161540085P | 2011-09-28 | 2011-09-28 | |
| EP11183034.5 | 2011-09-28 | ||
| EP11183034 | 2011-09-28 | ||
| US61/540,085 | 2011-09-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2013045600A1 true WO2013045600A1 (en) | 2013-04-04 |
Family
ID=47994311
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2012/069166 WO2013045600A1 (en) | 2011-09-28 | 2012-09-28 | Novel peptide derivatives as antibiotics |
Country Status (10)
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016046409A1 (en) * | 2014-09-26 | 2016-03-31 | Nosopharm | Novel peptide derivatives and uses thereof |
| WO2024200838A1 (en) * | 2023-03-31 | 2024-10-03 | Nosopharm | New odilorhabdins analogues as antibiotics against multi-resistant bacteria |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9800971B2 (en) | 2015-03-17 | 2017-10-24 | Knowles Electronics, Llc | Acoustic apparatus with side port |
| US11667674B2 (en) | 2016-04-08 | 2023-06-06 | Versitech Limited | Antibacterial cyclic lipopeptides |
| US10647746B2 (en) | 2016-04-08 | 2020-05-12 | Versitech Limited | Antibacterial cyclic lipopeptides |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2207433A (en) * | 1987-07-22 | 1989-02-01 | Nat Res Dev | Peptides |
| WO2002055545A1 (fr) * | 2001-01-12 | 2002-07-18 | Rhobio | Pseudopeptides antimicrobiens |
| WO2010136532A1 (fr) * | 2009-05-27 | 2010-12-02 | Nosopharm | Procédé pour augmenter la diversité des métabolites secondaires d'intérêt produits par des micro-organismes |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110033389A1 (en) * | 2009-04-29 | 2011-02-10 | Zhifeng Chen | Modified antibodies for passive immunotherapy |
-
2012
- 2012-09-28 JP JP2014532400A patent/JP6158188B2/ja active Active
- 2012-09-28 ES ES12778971.7T patent/ES2657930T3/es active Active
- 2012-09-28 RU RU2014114996/04A patent/RU2014114996A/ru not_active Application Discontinuation
- 2012-09-28 WO PCT/EP2012/069166 patent/WO2013045600A1/en active Application Filing
- 2012-09-28 US US14/342,446 patent/US9260481B2/en active Active
- 2012-09-28 IN IN3010DEN2014 patent/IN2014DN03010A/en unknown
- 2012-09-28 CA CA2845735A patent/CA2845735A1/en not_active Abandoned
- 2012-09-28 CN CN201280046610.4A patent/CN103827138B/zh active Active
- 2012-09-28 EP EP12778971.7A patent/EP2760881B1/en active Active
-
2014
- 2014-03-23 IL IL231664A patent/IL231664A0/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2207433A (en) * | 1987-07-22 | 1989-02-01 | Nat Res Dev | Peptides |
| WO2002055545A1 (fr) * | 2001-01-12 | 2002-07-18 | Rhobio | Pseudopeptides antimicrobiens |
| WO2010136532A1 (fr) * | 2009-05-27 | 2010-12-02 | Nosopharm | Procédé pour augmenter la diversité des métabolites secondaires d'intérêt produits par des micro-organismes |
Non-Patent Citations (10)
| Title |
|---|
| "Remington's Pharmaceutical Sciences", 1997, KRIEGER PUBLISHING COMPANY |
| BERDY J., J. ANTIBIOT., vol. 58, 2005, pages 1 - 26 |
| BODANZKY ET AL.: "The Practice of Peptide Synthesis", 1994, SPRINGER-VERLAG |
| FORST & K NEALSON S: "Molecular biology of the symbiotic-pathogenic bacteria Xenorhabdus spp. and Photorhabdus spp", MICROBIOLOGICAL REVIEWS, AMERICAN SOCIETY FOR MICROBIOLOGY, WASHINGTON, DC, US, vol. 60, no. 1, 1 March 1996 (1996-03-01), pages 21 - 43, XP002092718, ISSN: 0146-0749 * |
| GILBERT BANKER; CHRISTOPHER RHODES: "Modern Pharmaceutics", vol. 121, 2002, CRC PRESS |
| MARION D. ET AL., J. MAGN. RESON., vol. 85, 1989, pages 393 - 399 |
| NOLDEN S ET AL: "Analysis of RegA, a pathway-specific regulator of the friulimicin biosynthesis in Actinoplanes friuliensis", JOURNAL OF BIOTECHNOLOGY, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 140, no. 1-2, 10 March 2009 (2009-03-10), pages 99 - 106, XP025969909, ISSN: 0168-1656, [retrieved on 20090310], DOI: 10.1016/J.JBIOTEC.2008.12.013 * |
| PIOTTO M. ET AL., J. BIOMOL. NMR, vol. 2, 1992, pages 661 - 665 |
| REMINGTON: "The Science and Practice of Pharmacy", 2005, LIPPINCOT, WILLIAMS & WILKINS |
| WUTHRICH K.: "NMR of Proteins and Nucleic Acids", 1986, JOHN WILEY & SONS |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016046409A1 (en) * | 2014-09-26 | 2016-03-31 | Nosopharm | Novel peptide derivatives and uses thereof |
| KR20170057400A (ko) * | 2014-09-26 | 2017-05-24 | 노소팜 | 신규의 펩티드 유도체 및 그 용도 |
| JP2017533890A (ja) * | 2014-09-26 | 2017-11-16 | ノソファルムＮｏｓｏｐｈａｒｍ | 新規ペプチド誘導体およびその使用 |
| US10626144B2 (en) | 2014-09-26 | 2020-04-21 | Nosopharm | Peptide derivatives and uses thereof |
| AU2015323713B2 (en) * | 2014-09-26 | 2020-04-23 | Nosopharm | Novel peptide derivatives and uses thereof |
| JP2021100939A (ja) * | 2014-09-26 | 2021-07-08 | ノソファルムＮｏｓｏｐｈａｒｍ | 新規ペプチド誘導体およびその使用 |
| JP7123559B2 (ja) | 2014-09-26 | 2022-08-23 | ノソファルム | 新規ペプチド誘導体およびその使用 |
| KR102522224B1 (ko) * | 2014-09-26 | 2023-04-14 | 노소팜 | 신규의 펩티드 유도체 및 그 용도 |
| WO2024200838A1 (en) * | 2023-03-31 | 2024-10-03 | Nosopharm | New odilorhabdins analogues as antibiotics against multi-resistant bacteria |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2760881A1 (en) | 2014-08-06 |
| CA2845735A1 (en) | 2013-04-04 |
| IL231664A0 (en) | 2014-05-28 |
| ES2657930T3 (es) | 2018-03-07 |
| JP2014534173A (ja) | 2014-12-18 |
| IN2014DN03010A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2015-05-08 |
| EP2760881B1 (en) | 2017-11-01 |
| US9260481B2 (en) | 2016-02-16 |
| US20150175659A1 (en) | 2015-06-25 |
| CN103827138A (zh) | 2014-05-28 |
| RU2014114996A (ru) | 2015-11-10 |
| JP6158188B2 (ja) | 2017-07-05 |
| CN103827138B (zh) | 2016-05-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9260481B2 (en) | Peptide derivatives as antibiotics | |
| US8299020B2 (en) | Antimicrobial peptides and methods of their use | |
| US11548916B2 (en) | Anti-infective compound | |
| Ning et al. | Characterization of brevilaterins, multiple antimicrobial peptides simultaneously produced by Brevibacillus laterosporus S62-9, and their application in real food system | |
| Hicks | Antibacterial and anticancer activity of a series of novel peptides incorporating cyclic tetra-substituted Cα amino acids | |
| EP2500022B1 (en) | Antibacterial agent for drug-resistant bacteria and use of same | |
| EP3111948A1 (en) | New bicyclic lipopeptide, preparation and use as antimicrobial agent | |
| Hashizume et al. | Tripropeptin E, a new tripropeptin group antibiotic produced by Lysobacter sp. BMK333-48F3 | |
| Ji et al. | Isolation and characterization of two novel antibacterial cyclic hexapeptides from Streptomyces alboflavus 313 | |
| Maffioli | A Chemist's Survey of Different Antibiotic Classes | |
| KR102158205B1 (ko) | 항균 활성을 갖는 신규한 고리형 리포펩타이드계 화합물 및 이의 용도 | |
| WO2012085177A1 (en) | Nemaucin, an antibiotic produced by entomopathogenic xenorhabdus cabanillasii | |
| KR101344083B1 (ko) | 폴리사이클릭 펩타이드 화합물을 포함하는 항균용 조성물 및 이의 생산방법 | |
| KR102167324B1 (ko) | 백본-고리형 펩타이드와의 조합물 | |
| Sztaricskai et al. | A new series of glycopeptide antibiotics incorporating a squaric acid moiety | |
| Dubkara et al. | Discovery of a potent ornithine-modified gramicidin S analogue against drug-resistant Staphylococcus aureus and Enterococcus faecalis with minimal red blood cell toxicity | |
| Hashizume et al. | A new type of tripropeptin with anteiso-branched chain fatty acid from Lysobacter sp. BMK333-48F3 | |
| Guan et al. | A facile and selective derivatization approach on kynurenine-NH2 in daptomycin, leading to the discovery of hexakynomycin to combat multidrug-resistant Gram-positive pathogens especially daptomycin-resistant bacteria | |
| Miller et al. | Shipworm symbiosis ecology-guided discovery of Gram-negative selective antibiotic with activity against Acinetobacter | |
| KR101987854B1 (ko) | 고리형 헥사펩타이드계 화합물들 및 이의 용도 | |
| EP4132945A2 (en) | Antibacterial lipopeptides, pharmaceutical composition and cosmetic composition comprising them, and uses thereof | |
| Madu | Exploring the Antimicrobial Potential of Small Molecule Produced by Streptomyces Davawensis | |
| WO2024018398A1 (en) | Lipooligoureas, pharmaceutical composition, and lipooligoureas for use as medicament | |
| CN120623264A (zh) | 一种抗菌肽lk-kjt-b01及其制备方法和应用 | |
| Ladell | Isolation and characterization of antibiotics produced by the nematode symbiont Xenorhabdus szentirmaii |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 12778971 Country of ref document: EP Kind code of ref document: A1 |
|
| ENP | Entry into the national phase |
Ref document number: 2845735 Country of ref document: CA |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 14342446 Country of ref document: US |
|
| REEP | Request for entry into the european phase |
Ref document number: 2012778971 Country of ref document: EP |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 2012778971 Country of ref document: EP |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 231664 Country of ref document: IL |
|
| ENP | Entry into the national phase |
Ref document number: 2014532400 Country of ref document: JP Kind code of ref document: A |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| ENP | Entry into the national phase |
Ref document number: 2014114996 Country of ref document: RU Kind code of ref document: A |
|
| REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112014005710 Country of ref document: BR |
|
| REG | Reference to national code |
Ref country code: BR Ref legal event code: B01E Ref document number: 112014005710 Country of ref document: BR |
|
| ENPW | Started to enter national phase and was withdrawn or failed for other reasons |
Ref document number: 112014005710 Country of ref document: BR Free format text: PEDIDO RETIRADO EM RELACAO AO BRASIL POR NAO ATENDER AS DETERMINACOES REFERENTES A ENTRADA DO PEDIDO NA FASE NACIONAL E POR NAO CUMPRIMENTO DA EXIGENCIA FORMULADA NA RPI NO 2436 DE 12/09/2017. Ref document number: 112014005710 Country of ref document: BR |