CN103910681A - Metronidazole chalcone derivatives, and preparation method thereof and application utilizing antibacterial activity thereof - Google Patents
Metronidazole chalcone derivatives, and preparation method thereof and application utilizing antibacterial activity thereof Download PDFInfo
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- CN103910681A CN103910681A CN201310008105.7A CN201310008105A CN103910681A CN 103910681 A CN103910681 A CN 103910681A CN 201310008105 A CN201310008105 A CN 201310008105A CN 103910681 A CN103910681 A CN 103910681A
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- metronidazole
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- 229960000282 metronidazole Drugs 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 8
- -1 Metronidazole chalcone derivatives Chemical class 0.000 title abstract description 6
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims description 16
- GVSPXQVUXHMUMA-MDWZMJQESA-N (e)-3-(3,5-ditert-butyl-4-hydroxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one Chemical compound C1=CC(OC)=CC=C1C(=O)\C=C\C1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 GVSPXQVUXHMUMA-MDWZMJQESA-N 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000012043 crude product Substances 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 238000013019 agitation Methods 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 239000000047 product Substances 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 229940088710 antibiotic agent Drugs 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 239000012266 salt solution Substances 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 abstract description 10
- 241000193388 Bacillus thuringiensis Species 0.000 abstract description 9
- 229940097012 bacillus thuringiensis Drugs 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 7
- 244000063299 Bacillus subtilis Species 0.000 abstract description 5
- 235000014469 Bacillus subtilis Nutrition 0.000 abstract description 5
- 241000588724 Escherichia coli Species 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 3
- 230000005764 inhibitory process Effects 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 241000894006 Bacteria Species 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 6
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 6
- 229960004756 ethanol Drugs 0.000 description 6
- 230000001580 bacterial effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 229940023064 escherichia coli Drugs 0.000 description 4
- 230000000968 intestinal effect Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000000452 restraining effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 3
- 244000124209 Crocus sativus Species 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- SUYSQRHNTDVWKJ-UHFFFAOYSA-N 1,3-dichlorobenzene;formaldehyde Chemical compound O=C.ClC1=CC=CC(Cl)=C1 SUYSQRHNTDVWKJ-UHFFFAOYSA-N 0.000 description 1
- ZCJAYDKWZAWMPR-UHFFFAOYSA-N 1-chloro-2-fluorobenzene Chemical compound FC1=CC=CC=C1Cl ZCJAYDKWZAWMPR-UHFFFAOYSA-N 0.000 description 1
- OACPOWYLLGHGCR-UHFFFAOYSA-N 2-chloro-6-fluorobenzaldehyde Chemical compound FC1=CC=CC(Cl)=C1C=O OACPOWYLLGHGCR-UHFFFAOYSA-N 0.000 description 1
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
- YZEUHQHUFTYLPH-UHFFFAOYSA-N 2-nitroimidazole Chemical group [O-][N+](=O)C1=NC=CN1 YZEUHQHUFTYLPH-UHFFFAOYSA-N 0.000 description 1
- ZVTWZSXLLMNMQC-UHFFFAOYSA-N 4-phenylmethoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCC1=CC=CC=C1 ZVTWZSXLLMNMQC-UHFFFAOYSA-N 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 244000283207 Indigofera tinctoria Species 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- REAYFGLASQTHKB-UHFFFAOYSA-N [2-[3-(1H-pyrazol-4-yl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound N1N=CC(=C1)C=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 REAYFGLASQTHKB-UHFFFAOYSA-N 0.000 description 1
- AQDKESUPEHLLQC-SNAWJCMRSA-N [O-][N+](c1cnc(/C=C/c(c(Cl)ccc2)c2F)[n]1CCO)=O Chemical compound [O-][N+](c1cnc(/C=C/c(c(Cl)ccc2)c2F)[n]1CCO)=O AQDKESUPEHLLQC-SNAWJCMRSA-N 0.000 description 1
- VPOIHQRBTSQBLC-VOTSOKGWSA-N [O-][N+](c1cnc(/C=C/c2ccccc2)[n]1CCO)=O Chemical compound [O-][N+](c1cnc(/C=C/c2ccccc2)[n]1CCO)=O VPOIHQRBTSQBLC-VOTSOKGWSA-N 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940058965 antiprotozoal agent against amoebiasis and other protozoal diseases nitroimidazole derivative Drugs 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 108010079058 casein hydrolysate Proteins 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 206010014881 enterobiasis Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/91—Nitro radicals
- C07D233/92—Nitro radicals attached in position 4 or 5
- C07D233/94—Nitro radicals attached in position 4 or 5 with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to other ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/91—Nitro radicals
- C07D233/92—Nitro radicals attached in position 4 or 5
- C07D233/95—Nitro radicals attached in position 4 or 5 with hydrocarbon radicals, substituted by nitrogen atoms, attached to other ring members
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
Metronidazole chalcone derivatives have the general formula shown in the specification. The metronidazole chalcone derivatives have different-degree inhibition effects on escherichia coli, pseudomonas aeruginosa, bacillus thuringiensis and bacillus subtilis, so that the metronidazole chalcone derivatives are applicable to prepare antibacterial medicines. The invention discloses a preparation method for the metronidazole chalcone derivatives.
Description
Technical field
The present invention relates to novel metronidazole chalcone derivative of a class and preparation method thereof and purposes as antibacterials.
Background technology
" superbacteria " is bacterial drug resistance and multidrug resistant, is the outer clinical serious thorny problem running in anti-infective of Now Domestic.In China, bacterial resistance situation allows of no optimist, and Pseudomonas aeruginosa, the Acinetobacter bauamnnii etc. of general resistance become the important pathogen of ward infection.The reason that causes resistant organism is very complicated, is a social concern.Such as the research and development of microbiotic new product are slow, do not catch up with the variation paces of bacterium etc.Therefore, the research and development of new drug become new problem.
Metronidazole Tablet is nitro imidazole derivatives, anaerobion is had to killing action, and the metabolite generating when it reduces in human body also has anaerobe resistant effect, anti-bacteria thymus nucleic acid synthetic, thereby disturb growth, the breeding of bacterium, finally cause bacterium death.
Cinnamophenone is not only a kind of important organic synthesis intermediate, also has multiple pharmacological effect.Because its molecular structure has larger flexibility, can from different receptors bind, therefore there is biological activity widely.According to related documents, many cinnamophenone compounds have anti-pinworm, antitumor, suppress and remove the biological activitys such as oxyradical, antibacterial, antiviral, antiulcer agent and spasmolysis.
Therefore, we modify metronidazole, form cinnamophenone structure, reach the effect that strengthens its anti-microbial activity.We have tested the biological activity of this batch of compound, and find that it is to intestinal bacteria (Escherichiacoli), Pseudomonas aeruginosa (Pseudomonas aeruginosa), Bacillus thuringiensis (Bacillus thuringiensis) and subtilis (Bacillus subtilis) have good restraining effect.
Summary of the invention
The object of the present invention is to provide novel metronidazole chalcone derivative of a class and preparation method thereof and purposes.Technical scheme of the present invention is as follows:
The metronidazole chalcone derivative that one class is novel, it has following general formula:
In formula, R is:
The method for making of the above-mentioned metronidazole chalcone derivative of one class, it is made up of the following step:
Step. under agitation successively metronidazole, organic solvent, aldehyde, inorganic salt solution are joined in reaction vessel by a certain percentage, react for some time at a certain temperature (TLC monitors reaction), after reaction finishes, to adding appropriate water in reactant or direct filtration obtains thick product, crude product is through column chromatography or adopt the suitable organic solvent recrystallization target compound of purifying to obtain.
Embodiment:
Further describe the present invention by following examples, but scope of the present invention is not subject to any restriction of these embodiment.
Embodiment mono-: 2-(2-(2-fluorobenzene ethene)-5-nitro-1 hydrogen-imidazoles-1-) ethanol
Under agitation successively by metronidazole (1.7g, 10mmol), DMSO (10mL), o fluorobenzaldehyde (1.2g, 10mmol), the methanol solution (0.8g of sodium methylate, 15mmol) join in 250mL round-bottomed flask, after 3.5 hours, (TLC follows the tracks of reaction to 35 DEG C of stirring reactions of constant temperature; Developping agent: V
methylene dichloride: V
ethyl acetate=2: 1), reaction solution is poured in distilled water (300mL), filtered to obtain crude product, the crude product obtaining is dissolved in to the purification of dehydrated alcohol recrystallization and obtains faint yellow target compound.Productive rate 69.2%, m.p.77-80 DEG C;
1h NMR (DMSO-d
6, 300MHz) and δ: 8.22 (d, J=4.74,1H, CH), 7.82～7.70 (m, 3H, ArH), 7.64 (d, J=5.4Hz, 1H, CH), 7.42～7.30 (m, 2H, ArH, CH), 5.15～4.94 (m, 1H, OH), 4.54 (t, J=8.4Hz, 2H, CH
2), 3.77～3.70 (m, 2H, CH
2) .ESI-MS:278.09 (C
13h
13fN
3o
3, [M+H]
+) .Anal.Calcd forC
13h
12fN
3o
3: C, 56.32; H, 4.36; N, 15.16.Found:C, 54.20; H, 4.34; N, 14.78%.
Embodiment bis-: 2-(2-(the chloro-6-fluorobenzene of 2-ethene)-5-nitro-1-hydrogen-imidazoles-1-) ethanol
Preparation method, with embodiment mono-, replaces o fluorobenzaldehyde with the chloro-6-fluorobenzaldehyde of 2-, obtains yellow target compound, productive rate 72.5%, m.p.86-88 DEG C;
1h NMR (DMSO-d
6, 300MHz) and δ: 8.05 (s, 1H, CH), 7.67～7.38 (m, 4H, ArH, CH), 6.78 (d, J=5.4Hz, 1H, CH), 4.97 (t, J=5.6Hz, 1H, OH), 4.35 (t, J=6.0Hz, 2H, CH
2), 3.68～3.53 (m, 6H, CH
2) .ESI-MS:314.06 (C
13h
14clFN
3o
3, [M+H]
+) .Anal.Calcd for C
13h
13clFN
3o
3: C, 49.77; H, 4.18; N, 13.39.Found:C, 48.38; H, 4.14; N, 12.27%.
Embodiment tri-: 2-(2-(2,4 dichloro benzene ethene)-5-nitro-1 hydrogen-imidazoles-1-) ethanol
Preparation method, with embodiment mono-, replaces o fluorobenzaldehyde with 2,4 dichloro benzene formaldehyde, obtains yellow target compound, productive rate 69.5%, m.p.85-88 DEG C;
1h NMR (DMSO-d
6, 300MHz) and δ: 8.00 (s, 1H, CH), 7.65～7.43 (m, 2H, ArH), 7.37～7.20 (m, 2H, ArH, CH), 6.94 (d, J=8.5Hz, H, CH), 4.57 (t, J=6.1Hz, 1H, OH), 4.38 (t, J=9.6Hz, 2H, CH
2), 3.72～3.57 (m, 2H, CH
2) .ESI-MS:330.03 (C
13h
14cl
2n
3o
3, [M+H]
+) .Anal.Calcd for C
13h
13cl
2n
3o
3: C, 47.29; H, 3.97; N, 12.73.Found:C, 45.35; H, 3.95; N, 12.53%.
Embodiment tetra-: 2-(5-nitro-2-(2-nitrostyrolene)-1 hydrogen-imidazoles-1-) ethanol
Preparation method, with embodiment mono-, replaces o fluorobenzaldehyde with Ortho Nitro Benzaldehyde,, obtain safran target compound., productive rate 72.1%, m.p.77-80 DEG C;
1h NMR (DMSO-d
6, 300MHz) and δ: 8.25 (d, J=6.73Hz, 1H, CH), 8.03～7.94 (m, 3H, ArH, CH), 7.83～7.58 (m, 3H, ArH, CH), 4.99 (t, J=6.3Hz, 1H, OH), 4.54 (t, J=5.4Hz, 2H, CH
2), 3.74～3.52 (m, 2H, CH
2) .ESI-MS:305.08 (C
13h
13n
4o
5, [M+H]
+) .Anal.Calcd for C
13h
12n
4o
5: C, 51.32; H, 3.98; N, 18.41.Found:C, 49.26; H, 3.94; N, 16.54%.
Embodiment five: 2-(2-(4-(dimethylin) vinylbenzene)-5-nitro-1 hydrogen-imidazoles-1-) ethanol
Preparation method is with embodiment mono-, so that dimethylin phenyl aldehyde is replaced to o fluorobenzaldehyde, and, obtain yellow target compound. and, productive rate 68.4%, m.p.86-88 DEG C;
1h NMR (DMSO-d
6, 300MHz) and δ: 8.06 (s, 1H, CH), 7.83～7.70 (m, 2H, ArH), 7.00～6.73 (m, 2H, ArH), 6.97 (t, J=6.7Hz, 2H, CH), 5.00 (t, J=6.2Hz, 1H, OH), 4.37 (t, J=7.4Hz, 2H, CH
2), 3.68～3.53 (m, 2H, CH
2), 1.46～1.19 (m, 6H, CH
3) .ESI-MS:305.15 (C
15h
19n
4o
3, [M+H]
+) .Anal.Calcd forC
15h
18n
4o
3: C, 59.59; H, 6.00; N, 18.53.Found:C, 43.87; H, 6.03; N, 17.73%.
Embodiment six: 2-(2-(4-(benzyloxy) vinylbenzene)-5-nitro-1 hydrogen-imidazoles-1-) ethanol
Preparation method, with embodiment mono-, replaces o fluorobenzaldehyde with P-benzyloxybenzaldehyde,, obtain safran target compound, productive rate 72.3%, m.p.84-87 DEG C;
1h NMR (DMSO-d
6, 300MHz) and δ: 7.99 (d, J=5.8Hz, 1H, CH) 7.64～7.50 (m, 4H, ArH), 7.42～7.26 (m, 3H, ArH), 7.08～6.90 (m, 4H, Ar, CH), 5.16 (t, J=5.1Hz, 2H, CH
2), 4.54 (t, J=6.7Hz, 1H, OH), 4.39 (t, J=8.3Hz, 2H, CH
2), 3.68～3.54 (m, 2H, CH
2) .ESI-MS:366.14 (C
20h
21n
3o
4, [M+H]
+) .Anal.Calcd for C
20h
19n
3o
4: C, 65.74; H, 5.24; N, 11.50.Found:C, 63.83; H, 5.23; N, 12.98%.
Seven: one class metronidazole derivative antibacterial activity researchs of embodiment
Adopt MTT[3-(4,5)-bis-methyl-2-thiazoles-(2,5)-phenyl bromination tetrazole indigo plant] method carrys out measure and calculation metronidazole chalcone derivative to intestinal bacteria (Escherichia coli), Pseudomonas aeruginosa (Pseudomonasaeruginosa), the half-inhibition concentration (IC of Bacillus thuringiensis (Bacillus thuringiensis) and subtilis (Bacillus subtilis)
50).
(1) preparation of substratum
Get beef extract powder 5g, casein hydrolysate 17.5g, starch 1.5g, agar 12.5g, adds in 1000mL distilled water, and heated and boiled is dissolved, packing, 121 DEG C of autoclavings 15 minutes are for subsequent use.
(2) cultivation of test organisms
In sterilisable chamber, get intestinal bacteria (Escherichia coli), Pseudomonas aeruginosa (Pseudomonasaeruginosa), Bacillus thuringiensis (Bacillus thuringiensis) and four kinds of test strains of subtilis (Bacillus subtilis), under spirit lamp with inoculating needle respectively on four kinds of test strain inclined-planes, scrape the inclined-plane lawn that takes a morsel, make bacteria suspension with a certain amount of sterilized water, then getting a certain amount of being added to melts and is cooled in the MH substratum of 50 DEG C of left and right, shake up, at once pour in sterile petri dish, after sealing with plug after abundant condensation, in 37 DEG C cultivate 18-24 hour for subsequent use.Draw bacterium liquid 1mL, by dilution in 1: 100000, make bacterial concentration be about 10 with MH substratum
3cfu/mL.
(3) antibacterial experiment:
Medicine to be measured is dissolved in to the solution that is mixed with 2mg/mL in DMSO, then medicine is diluted in finite concentration gradient (160 μ g/mL, 40 μ g/mL, 10 μ g/mL, 2.5 μ g/mL) and DMSO.In sterilizing microtiter plate Article 1, add respectively the DMSO of 10 μ L and the bacteria suspension of 90 μ L as blank, the positive contrast of Article 2, adds penicillin and the kantlex of 90 μ L bacteria suspensions and 10 μ L.In remaining hole, add the bacteria suspension of 90 μ L and the drug solution of 10 μ L.Parallel 3 times of each drug solution concentration.Indicate bacteria name in microtiter plate bottom.
(4) IC
50mensuration
The culture dish of handling, in 37 DEG C of cultivation 24h, is squeezed into 10 μ L MTT liquid (2mg/ml) and cultivated 4h again.Centrifugal, supernatant liquor to be outwelled, every hole adds the DMSO of 150 μ L to dissolve, and microplate reader is measured its absorbancy OD value, calculates bacterial growth inhibiting rate by following formula.The results are shown in Table 1.
Growth inhibition ratio=(the average OD value/blank of 1-medication group group OD value) * 100%
Half-inhibition concentration (IC
50) be defined as the drug level in the time of 50% bacteria living.According to the optical density(OD) (OD value) of measuring, make the typical curve of bacterial growth inhibiting rate, on typical curve, try to achieve its corresponding drug level.
The restraining effect of table 1 compound 1-6 to bacterial growth
Result shows: this serial metronidazole chalcone derivative is to intestinal bacteria (Escherichia coli), Pseudomonas aeruginosa (Pseudomonas aeruginosa), Bacillus thuringiensis (Bacillus thuringiensis) and subtilis (Bacillus subtilis) have restraining effect in various degree.
Claims (3)
1. a class metronidazole chalcone derivative, is characterized in that it has following general formula:
In formula, R is:
2. prepare a method for metronidazole chalcone derivative claimed in claim 1, it is characterized in that it is made up of the following step:
Under agitation successively metronidazole, organic solvent, aldehyde, inorganic salt solution are joined in reaction vessel by a certain percentage, react for some time at a certain temperature (TLC monitors reaction), after reaction finishes, to adding appropriate water in reactant or direct filtration obtains thick product, crude product is through column chromatography or adopt the suitable organic solvent recrystallization target compound of purifying to obtain.
3. the application of metronidazole chalcone derivative according to claim 1 in preparation antibacterials.
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