CN116425804A - Cyclometalated iridium complex with anti-inflammatory and anti-tumor activities and preparation method and application thereof - Google Patents
Cyclometalated iridium complex with anti-inflammatory and anti-tumor activities and preparation method and application thereof Download PDFInfo
- Publication number
- CN116425804A CN116425804A CN202310359647.2A CN202310359647A CN116425804A CN 116425804 A CN116425804 A CN 116425804A CN 202310359647 A CN202310359647 A CN 202310359647A CN 116425804 A CN116425804 A CN 116425804A
- Authority
- CN
- China
- Prior art keywords
- inflammatory
- iridium complex
- formula
- tumor
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229910052741 iridium Inorganic materials 0.000 title claims abstract description 49
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 230000000259 anti-tumor effect Effects 0.000 title claims abstract description 30
- 230000003110 anti-inflammatory effect Effects 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 206010061218 Inflammation Diseases 0.000 claims abstract description 18
- 230000004054 inflammatory process Effects 0.000 claims abstract description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 25
- GIEQBYJCGYHHSU-UHFFFAOYSA-N 4,7-dichloro-1,10-phenanthroline Chemical compound C1=CC2=C(Cl)C=CN=C2C2=C1C(Cl)=CC=N2 GIEQBYJCGYHHSU-UHFFFAOYSA-N 0.000 claims description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 15
- 239000002243 precursor Substances 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 10
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 10
- 201000010881 cervical cancer Diseases 0.000 claims description 10
- -1 saturated ammonium hexafluorophosphate Chemical class 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 230000028709 inflammatory response Effects 0.000 claims description 8
- 239000002244 precipitate Substances 0.000 claims description 6
- 239000012046 mixed solvent Substances 0.000 claims description 5
- 229940041181 antineoplastic drug Drugs 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 229940124599 anti-inflammatory drug Drugs 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000002503 iridium Chemical class 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 abstract description 32
- 108090000623 proteins and genes Proteins 0.000 abstract description 27
- 102000004169 proteins and genes Human genes 0.000 abstract description 19
- 230000002757 inflammatory effect Effects 0.000 abstract description 18
- 230000006907 apoptotic process Effects 0.000 abstract description 10
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 abstract description 8
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 abstract description 8
- 210000003470 mitochondria Anatomy 0.000 abstract description 6
- 102100030497 Cytochrome c Human genes 0.000 abstract description 5
- 108010075031 Cytochromes c Proteins 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 5
- 230000037361 pathway Effects 0.000 abstract description 4
- 102000055102 bcl-2-Associated X Human genes 0.000 abstract description 3
- 108700000707 bcl-2-Associated X Proteins 0.000 abstract description 3
- 230000002222 downregulating effect Effects 0.000 abstract description 3
- 210000004969 inflammatory cell Anatomy 0.000 abstract description 3
- 230000009462 endogenous apoptosis Effects 0.000 abstract description 2
- 239000000460 chlorine Substances 0.000 description 9
- 239000003446 ligand Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- 102000004889 Interleukin-6 Human genes 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 6
- 229940100601 interleukin-6 Drugs 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 230000002438 mitochondrial effect Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 102000000589 Interleukin-1 Human genes 0.000 description 3
- 108010002352 Interleukin-1 Proteins 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 208000038016 acute inflammation Diseases 0.000 description 3
- 230000006022 acute inflammation Effects 0.000 description 3
- 230000001640 apoptogenic effect Effects 0.000 description 3
- 230000005775 apoptotic pathway Effects 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000004925 denaturation Methods 0.000 description 3
- 230000036425 denaturation Effects 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- WZJYKHNJTSNBHV-UHFFFAOYSA-N benzo[h]quinoline Chemical compound C1=CN=C2C3=CC=CC=C3C=CC2=C1 WZJYKHNJTSNBHV-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229940096397 interleukin-8 Drugs 0.000 description 2
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 210000001700 mitochondrial membrane Anatomy 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- LPCWDYWZIWDTCV-UHFFFAOYSA-N 1-phenylisoquinoline Chemical compound C1=CC=CC=C1C1=NC=CC2=CC=CC=C12 LPCWDYWZIWDTCV-UHFFFAOYSA-N 0.000 description 1
- QLPKTAFPRRIFQX-UHFFFAOYSA-N 2-thiophen-2-ylpyridine Chemical compound C1=CSC(C=2N=CC=CC=2)=C1 QLPKTAFPRRIFQX-UHFFFAOYSA-N 0.000 description 1
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 1
- 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108091092584 GDNA Proteins 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 231100000070 MTS assay Toxicity 0.000 description 1
- 238000000719 MTS assay Methods 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102000018745 NF-KappaB Inhibitor alpha Human genes 0.000 description 1
- 108010052419 NF-KappaB Inhibitor alpha Proteins 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000008576 chronic process Effects 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000006303 immediate early viral mRNA transcription Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 108091006086 inhibitor proteins Proteins 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000005776 mitochondrial apoptotic pathway Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000029553 photosynthesis Effects 0.000 description 1
- 238000010672 photosynthesis Methods 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 238000012257 pre-denaturation Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000025915 regulation of apoptotic process Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0033—Iridium compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1044—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1092—Heterocyclic compounds characterised by ligands containing sulfur as the only heteroatom
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/18—Metal complexes
- C09K2211/185—Metal complexes of the platinum group, i.e. Os, Ir, Pt, Ru, Rh or Pd
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a cyclometalated iridium complex with anti-inflammatory and anti-tumor activities, and a preparation method and application thereof, and belongs to the technical field of medicines. The cyclometalated iridium complex has a structure shown in formulas 1-3, has green fluorescence, can specifically target mitochondria of cells after entering the cells, induces apoptosis by adjusting the expression quantity of proteins such as Cytochrome c, bax, bcl-2 and the like in an endogenous apoptosis pathway of the mitochondria, has good anti-tumor activity and has concentration dependence. In addition, the cyclometallated iridium complex can inhibit RAW264.7 inflammatory cells induced by LPS by down-regulating the expression level of p-NF- κB and p-I κB proteins in inflammatory pathwaysThe model has good anti-inflammatory effect in inflammatory reaction.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a cyclometalated iridium complex with anti-inflammatory and anti-tumor activities, and a preparation method and application thereof.
Background
Cervical cancer is the second largest cancer affecting global woman health and life, and the traditional treatment methods for cervical cancer include surgery, radiotherapy, chemotherapy and the like, but all have the defects of strong invasiveness, poor targeting and high recurrence rate. Therefore, it is urgent to find efficient and safe cervical cancer treatment drugs, and to improve the survival rate and the survival quality of patients.
At present, induction of apoptosis is one of the most common modes in the action mechanism of antitumor drugs, and the apoptosis pathway is divided into exogenous apoptosis pathway and mitochondrial apoptosis pathway. When the cell's mitochondria are dysfunctional, a series of reactions affecting the normal physiological functions of tumor cells, such as decreased mitochondrial membrane potential, increased ROS levels, decreased ATP production, etc., are produced. Mitochondrial regulation of apoptosis is primarily manifested by the release of pro-apoptotic proteins affecting the mitochondrial membrane space, such as the B cell lymphoma protein 2 (Bcl-2) family, which activate the mitochondrial-controlled apoptosis effector mechanisms.
Inflammation is also called "inflammation" and is classified into acute or chronic inflammation, and acute inflammation carriers have positive auxiliary effects, while chronic inflammation tissues may mislead to activation of a collective defense system by activating immune cells, thereby causing inflammation to occur in various tissues and organs of an organism, and the acute inflammation carriers have negative effects. Inflammation is the underlying pathological process of many diseases. When an inflammatory factor stimulates the body, cells release specific inflammatory substances such as interleukin-8 (IL-8) produced by macrophages, histamine released by mast cells, interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and the like secreted by primary cells, thereby activating NF- κB signaling pathways, resulting in an inflammatory response in the body.
Studies have shown that a variety of diseases, including cancer, are highly associated with inflammation. Although there are a large number of anti-inflammatory drugs in clinic, they mostly cause adverse reactions such as gastrointestinal damage. Inflammation is closely related to tumorigenesis, metastasis and exacerbation, and inflammatory factors may interfere with key regulatory mechanisms, such as apoptosis and autophagy, thereby producing cancer. Clinically, the combined inflammation makes the treatment of cervical cancer difficult. The chronic process of inflammation can induce a large amount of inflammatory growth factors and active mediators to be generated in the tissue microenvironment, thereby causing the damage of genetic materials such as genes, DNA and the like, inducing the malignant growth of tissues around the inflammation and forming tumors. In addition, in the occurrence of cervical cancer, a large amount of active oxygen and free radicals exist, and damage to cervical cancer epithelial cells can be caused. These changes lead to a disruption of its own defensive functions, and the patient is more susceptible to infection, thereby producing inflammation. Eventually, the body is caused to develop "inflammatory-cancerous transformation".
Therefore, the invention can treat inflammation and tumor, which has great significance for clinical treatment of patients with malignant tumor complicated with inflammation.
Disclosure of Invention
In view of the above, the technical problem to be solved by the present invention is to provide a cyclometalated iridium complex with anti-inflammatory and antitumor activities, and a preparation method and application thereof. The cyclometalated iridium complex with anti-inflammatory and anti-tumor activities has good anti-tumor and anti-inflammatory activities.
The invention provides a cyclometalated iridium complex with anti-inflammatory and anti-tumor activities, which has any one structure of formulas 1-3:
preferably, the anion of the cyclometallated iridium complex is PF 6 -。
The above-mentioned components 1-3 are respectively combined with anionic PF 6 - The molecular formula of the obtained complex is [ Ir (C-N) 2 L](PF 6 ) 2 Wherein L is 4, 7-dichloro-1, 10-phenanthroline, and the complex is when C-N=7, 8-benzoquinolineIr1, C-N=1-phenylisoquinoline, ir2 and C-N=2- (2-thienyl) pyridine, ir3.
The invention also provides a preparation method of the cyclometalated iridium complex with anti-inflammatory and anti-tumor activities, which comprises the following steps:
and respectively mixing and reacting 4, 7-dichloro-1, 10-phenanthroline with iridium complex precursors with structures shown in formulas 4-6 to obtain corresponding cyclometalated iridium complexes with structures shown in formulas 1-3.
Preferably, X is halogen.
In a preferred embodiment of the present invention, the X is selected from chlorine atoms, and the above formula 4 is [ Ir (bzq) 2 Cl] 2 The formula 5 is [ Ir (piq) 2 Cl] 2 6 is [ Ir (thpy) 2 Cl] 2 。
In some embodiments of the present invention, the above preparation method is preferably:
iridium complex precursors having structures represented by formulas 4 to 6: bridged bis (7, 8-benzoquinoline) -monochloro-iridium (III) or bridged bis (1-phenylisoquinoline) -monochloro-iridium (III) or bridged bis (2- (2-thienyl) pyridine) -monochloro-iridium (III) and a ligand 4, 7-dichloro-1, 10-phenanthroline are stirred and refluxed in a dichloromethane/methanol mixed solution, after the reaction solution is cooled to room temperature, an excessive saturated ammonium hexafluorophosphate solution is added, and reddish brown or brown precipitate is separated out respectively, filtered, purified and dried to obtain an iridium complex Ir1 or Ir2 or Ir3.
Preferably, the molar ratio of the 4, 7-dichloro-1, 10-phenanthroline to the iridium complex precursor with the structure shown in the formula 4 is (1-3): 1; more preferably (1-2): 1. In some embodiments of the invention, the molar ratio is preferably 1:1.
Preferably, the molar ratio of the 4, 7-dichloro-1, 10-phenanthroline to the iridium complex precursor with the structure shown in the formula 5 is (1-3): 1; more preferably (1-2): 1; further preferably 1:1.
Preferably, the molar ratio of the 4, 7-dichloro-1, 10-phenanthroline to the iridium complex precursor with the structure shown in the formula 6 is (1-3): 1; more preferably (1-2): 1. In some embodiments of the invention, the molar ratio is preferably 1:1.
Preferably, the solvent for the reaction is selected from the group consisting of a mixed solvent of methylene chloride and methanol.
Preferably, the volume ratio of the dichloromethane to the methanol is (1-4): 1; more preferably (1-3): 1; further preferably 2:1.
Preferably, the temperature of the reaction is 40-55 ℃.
The iridium complex precursor with the structure shown in the formulas 4-6 and the ligand 4, 7-dichloro-1, 10-phenanthroline can be subjected to light-shielding treatment during the reaction, so that the relative stability of synthetic raw materials is maintained, the oxidation reaction is reduced, and the content of byproducts generated by the photosynthesis reaction in the reaction process is reduced. Preferably, the reaction further comprises the following steps after completion:
and adding a saturated ammonium hexafluorophosphate solution into the reaction system, removing the solvent after the reaction is finished, and adding the rest reaction solution into diethyl ether to separate out solid precipitate to obtain the cyclometallated iridium complex.
The invention also provides application of the cyclometalated iridium complex with anti-inflammatory and anti-tumor activities in preparation of anti-tumor and anti-inflammatory drugs.
The anti-tumor mechanism is to induce apoptosis and inhibit migration of cells. The iridium complex has good anti-tumor activity and can be used as a novel anti-tumor drug.
Preferably, the anti-tumor is an anti-solid tumor.
Preferably, the solid tumor is a cervical cancer cell (HeLa cell).
The complex provided by the invention has green fluorescence, can specifically target mitochondria, induce tumor cells to undergo apoptosis and inhibit migration of tumor cells, and has good cervical cancer resistance activity.
In addition, the iridium complex disclosed by the invention has little influence on the survival rate of inflammatory model cells in a certain concentration range, and can be used for detecting anti-inflammatory activity.
Preferably, the inflammation model cells are RAW264.7 cells.
Preferably, the anti-inflammatory inflammation is an inflammatory response induced by LPS in RAW264.7 cells.
Compared with the prior art, the cyclometalated iridium complex with anti-inflammatory and anti-tumor activities has the structure shown in the formulas 1-3. The cyclometalated iridium complex has green fluorescence, can specifically target mitochondria of cells after entering the cells, induces apoptosis by regulating the expression levels of proteins such as Cytochrome c, bax, bcl-2 and the like in endogenous apoptosis channels of the mitochondria, has good anti-tumor activity and has concentration dependence. In addition, the cyclometallated iridium complex can inhibit inflammatory response of RAW264.7 inflammatory cell model induced by LPS by down-regulating the expression level of p-NF- κB and p-I κB proteins in inflammatory pathways, and has good anti-inflammatory effect.
Drawings
FIG. 1 is a graph of RAW264.7 cell viability at different concentrations of complex Ir 1;
FIG. 2 is a graph of mRNA transcription level of RAW264.7 cell inflammatory factor;
FIG. 3 is a graph showing the dose-dependent effect of the complex Ir1 on Bax and Bcl-2 apoptotic proteins;
FIG. 4 is a graph showing the dose-dependent effect of Ir1 complex on p-NF- κB and p-I κB inflammatory proteins.
Detailed Description
In order to further illustrate the present invention, the following describes in detail the cyclic iridium complexes with anti-inflammatory and antitumor activities, and the preparation methods and applications thereof, provided by the present invention, with reference to examples.
Example 1
(1) Ligand: 4, 7-dichloro-1, 10-phenanthroline was purchased from Sigma Co
(2) Preparation of Complex Ir1
4, 7-dichloro-1, 10-phenanthroline ligand (0.25 mmol,2 equiv) and iridium complex precursor [ Ir (bzq) 2 Cl] 2 (0.125 mmol,1 equiv) was added to a three-necked flask, followed by stirring and refluxing in a mixed solvent of 30mL of methylene chloride and 15mL of methanol (2:1, v/v), and the reaction was conducted under argon protection from light for 4 hours. After the reaction was completed, the mixture was cooled to room temperature, 6 times of supersaturated ammonium hexafluorophosphate was poured into the mixture, and stirring was continued for 2 hours. Concentrated to 2mL in a rotary evaporator, added dropwise to 20mL of diethyl ether to give a large amount of a dark red precipitate, filtered and dried to give a crude product, which was taken up in methylene chloride: the methanol (120:1, v/v) system was passed through a silica gel column and dried to give the brown target product Ir1 in 65.8% yield.
Elemental analysis C 38 H 22 Cl 2 IrN 4 (molecular weight 942.73), theoretical value: c57.21%; h2.78%; n,7.02%, experimental values: c57.24%, H2.82%, N7.10%. ESI-MS: [ (M-PF) 6 - )] + Theoretical value: m/z= 797.73, experimental values: m/z= 797.60.
Example 2
(1) Ligand: 4, 7-dichloro-1, 10-phenanthroline was purchased from Sigma Co
(2) Preparation of Complex Ir2
4, 7-dichloro-1, 10-phenanthroline ligand (0.25 mmol,2 equiv) and iridium complex precursor [ Ir (piq) 2 Cl] 2 (0.125 mmol,1 equiv) was added to a three-necked flask, followed by stirring and refluxing in a mixed solvent of 30mL of methylene chloride and 15mL of methanol (2:1, v/v), and the reaction was conducted under argon protection from light for 4 hours. After the reaction was completed, the mixture was cooled to room temperature, 6 times of supersaturated ammonium hexafluorophosphate was poured into the mixture, and stirring was continued for 2 hours. Concentrated to 2mL in a rotary evaporator, added dropwise to 20mL of diethyl ether to give a large amount of a dark red precipitate, filtered and dried to give a crude product, which was taken up in methylene chloride: the methanol (120:1, v/v) system was passed through a silica gel column and dried to give the reddish brown target product Ir2 in a 70.59% yield.
Elemental analysis C 42 H 26 Cl 2 IrN 4 (molecular weight 994.77), theoretical value: c59.36%; h3.08%; n6.59%, experimental values: 59.28% of C, 3.06% of H and 6.64% of N. ESI-MS: [ (M-PF) 6 - )] + Theoretical value: m/z= 849.81, experimental values: m/z= 849.20.
Example 3
(1) Ligand: 4, 7-dichloro-1, 10-phenanthroline was purchased from Sigma Co
(2) Preparation of Complex Ir3
4, 7-dichloro-1, 10-phenanthroline ligand (0.25 mmol,2 equiv) and iridium complex precursor [ Ir (thpy) 2 Cl] 2 (0.125 mmol,1 equiv) was added to a three-necked flask, followed by stirring and refluxing in a mixed solvent of 30mL of methylene chloride and 15mL of methanol (2:1, v/v), and the reaction was conducted under argon protection from light for 4 hours. After the reaction was completed, the mixture was cooled to room temperature, 6 times of supersaturated ammonium hexafluorophosphate was poured into the mixture, and stirring was continued for 2 hours. Concentrated to 2mL in a rotary evaporator, added dropwise to 20mL of diethyl ether to give a large amount of brown-green precipitate, filtered and dried to give a crude product, which was taken up in dichloromethane: the methanol (120:1, v/v) system was passed through a silica gel column and dried to give the brown-green target product Ir3 in a 71.26% yield.
Elemental analysis C 30 H 18 Cl 2 IrN 4 S 2 (molecular weight 906.70), theoretical value: c47.30%; h2.38%; n7.36%, experimental values: c47.41%, H2.36%, N7.30%. ESI-MS: [ (M-PF) 6 - )] + Theoretical value: m/z= 761.74, experimental values: m/z= 759.90.
Example 4
Toxicity study of cyclometallated iridium complex on tumor cells and inflammatory model cells
Cytotoxicity test (MTS method): the MTS method is a reliable, classical method for determining cytotoxicity of drugs, and the experimental procedure for tumor cell testing is as follows:
160 μl of the cell suspension was seeded in 96-well plates at a density of 5000 wells per well. After 24h incubation in a constant temperature carbon dioxide incubator, the cells were treated and 40 μl of 7 gradient concentrations of cyclometallated iridium complex diluted with medium was added to each well. After 48h of incubation, 20. Mu.L of MTS assay was added, respectively. Then, the incubation was continued for 3 hours, and the absorbance OD was measured by the upper machine.
The test results of HeLa cells are shown in table 1:
TABLE 1 toxicity test data for HeLa cells
IC 50 The concentration of the corresponding complex at 50% inhibition of the cells. The experimental data are the average values obtained after three parallel experiments. Experimental results show that the complexes Ir1-Ir3 have good activity of resisting HeLa cervical cancer, wherein the IC of the complex Ir1 50 Only 0.84 μm.
The effect of the complex Ir1 on RAW264.7 cytotoxicity is shown in fig. 1, and fig. 1 is a graph of RAW264.7 cell viability at different concentrations of complex Ir 1. Wherein, survival% = average OD value of dosing wells/average OD value of control wells x 100%. As shown in FIG. 1, RAW264.7 cell IC 50 It was 0.85. Mu.M, indicating that the complex Ir1 has an inhibitory effect on the activity of RAW264.7 cells.
In addition, when the concentration of the complex Ir1 is 0.5. Mu.M or less, the survival rate of RAW264.7 is more than 80%, so that the concentration of 0.5. Mu.M or less can be selected for the subsequent anti-inflammatory study.
Example 5
The anti-inflammatory activity of the complex Ir1 is judged by detecting the influence of iridium complex on the mRNA expression amounts of TNF-alpha, IL-6 and IL-1 beta of RAW264.7 cells through real-time fluorescence quantitative qRT-PCR.
Real-time fluorescent quantitative qRT-PCR method: RAW264.7 cells were cultured to logarithmic growth phase at 2X 10 6 The density of each well was inoculated into a 6-well culture dish, and a Control group, an LPS model group, and a cyclometalated iridium complex Ir1 administration group (0.5. Mu.M) were set. After the incubation of the drug for 1h, LPS (final concentration of 1 mg. Multidot.L) was added to each group except the Control group -1 ) Modeling inflammation, incubating for 24h, removing supernatant, and preparing RNA prep pureThe Cell kit provides instructions for extracting total cellular RNA. Next, the samples were quantified and stored in a-80℃refrigerator. cDNA was synthesized using a cDNA first strand synthesis premix reagent according to the method of FastKing gDNA Dispelling RT SuperMix kit, and stored in a-20℃refrigerator. The designed and synthesized specific gene primers and their sequences are shown in Table 2 below.
Table 2 specific Gene primer and sequence thereof
The premixed reagent was quantified by fluorescence of Super Real PreMix Plus and the reaction volume was 20. Mu.L. The conditions are that the pre-denaturation is carried out at 95 ℃ for 15min;40cycles of; denaturation at 95℃for 10s; annealing at 60 ℃ for 20s; extending at 72℃for 32s. The method adopts a SybrGreen ER fluorescence detection system method to calculate the result, carries out relative quantitative analysis on a target gene, takes beta-actin as an internal reference gene, carries out normalization treatment by contrasting with a Ct value, adopts 2 －△△Ct Quantitative PCR (reverse transcription) reactions were performed. After completion, ct values of the respective sample wells were recorded, and mRNA expression amounts of 4 target genes (IL-1β, IL-6, TNF-. Alpha., β -actin) were calculated. During the inflammatory response, the cells synthesize and release a number of inflammatory cytokines, such as IL-1. Beta., IL-6, TNF-alpha, etc., which are further activated, causing the organism to exhibit a series of inflammatory responses.
FIG. 2 is a graph showing mRNA transcription level of RAW264.7 cell inflammatory factor. As shown in FIG. 2, the transcription level of inflammatory factor mRNA was significantly increased in the LPS-stimulated RAW264.7 cell group compared to the blank group (Control group), indicating that the modeling was successful. In contrast to the LPS group, the mRNA expression levels of IL-1β, IL-6 and TNF- α of the Ir1 complex group were significantly reduced. Experiments prove that the complex Ir1 has the effect of inhibiting the release of inflammation-related factors.
FIG. 3 is a graph showing the dose-dependent effect of Ir1 complex on Bax and Bcl-2 apoptotic proteins. HeLa cells or RAW264.7 cells were inoculated into a 60mm cell culture dish, and when the cell density increased to about 70%, 3 concentrations of the complex Ir1 were added, and after 24 hours of wall-attached incubation, the cells were lysed and the proteins were collected. And (3) carrying out denaturation on the protein sample added with the loading buffer solution, and carrying out high-temperature denaturation for 10min. Then, proteins with different molecular weights are separated by gel electrophoresis, membrane transfer, sealing, primary antibody incubation and secondary antibody incubation are carried out, and finally protein strips are developed. Bax/Bcl-2 is a classical pair of apoptotic proteins, while the release of Cytochrome c (Cytochrome c) is a hallmark event of apoptosis in the mitochondrial apoptotic pathway.
As shown in FIG. 3, the results show that with the increase of the concentration of the complex Ir1, the protein expression amounts of Cytocohrome c (Cyto-c) and Bax are gradually increased, while the protein expression amount of Bcl-2 is reduced, which indicates that the complex Ir1 can induce apoptosis and has good anti-tumor activity.
On the other hand, the nuclear factor- κb (NF- κb) signaling pathway is a classical inflammatory response pathway, and in a normal state, NF- κb binds to the inhibitor protein ikb, and in an inactive state, when activated by inflammatory stimuli such as LPS, ikb is degraded, and NF- κb also dissociates into the nucleus and binds to the ikb sequence of the target gene, thereby inducing transcription of the related inflammatory factor gene. FIG. 4 is a graph showing the dose-dependent effect of Ir1 complex on p-NF- κB and p-I κB inflammatory proteins.
As shown in FIG. 4, the NF- κB and IκB α protein expression levels of LPS group were significantly increased compared with the control group, while the p-NF- κB and p-IκB α protein expression levels were gradually decreased with the increase in the concentration of the complex Ir1 compared with the LPS model group, indicating that it was able to inhibit the production of inflammatory factors, with good anti-inflammatory effect.
In conclusion, the cyclometallated iridium complex induces apoptosis by regulating the expression quantity of proteins such as Cytochrome c, bax, bcl-2 and the like in an endogenous mitochondrial apoptosis channel, has good anti-tumor activity and concentration dependence. In addition, the cyclometallated iridium complex can inhibit inflammatory response of RAW264.7 inflammatory cell model induced by LPS by down-regulating the expression level of p-NF- κB and p-I κB proteins in inflammatory pathways, and has good anti-inflammatory effect.
The above description of the embodiments is only for aiding in the understanding of the method of the present invention and its core ideas. It should be noted that it will be apparent to those skilled in the art that various modifications and adaptations of the invention can be made without departing from the principles of the invention and these modifications and adaptations are intended to be within the scope of the invention as defined in the following claims.
Claims (10)
1. A cyclometalated iridium complex having anti-inflammatory and antitumor activities, characterized by having any one of the structures of formulae 1 to 3:
formula 1:
formula 2:
formula 3:
2. the cyclometallated iridium complex with anti-inflammatory and anti-tumor activity according to claim 1, wherein the anion of the cyclometallated iridium complex is PF 6 - 。
3. A method for preparing a cyclometalated iridium complex with anti-inflammatory and anti-tumor activities, which is characterized by comprising the following steps:
mixing and reacting 4, 7-dichloro-1, 10-phenanthroline with iridium complex precursors with structures shown in formulas 4-6 to obtain corresponding cyclometalated iridium complexes with structures shown in formulas 1-3;
formula 4:
formula 5:
formula 6:
and X is halogen.
4. The method for producing a cyclometallated iridium complex having anti-inflammatory and antitumor activities according to claim 3, wherein the molar ratio of 4, 7-dichloro-1, 10-phenanthroline to iridium complex precursor having the structure represented by formula 4 is (1-3): 1;
the molar ratio of the 4, 7-dichloro-1, 10-phenanthroline to the iridium complex precursor with the structure shown in the formula 5 is (1-3) 1;
the molar ratio of the 4, 7-dichloro-1, 10-phenanthroline to the iridium complex precursor with the structure shown in the formula 6 is (1-3): 1.
5. The method for preparing a cyclometallated iridium complex having anti-inflammatory and antitumor activities according to claim 3, wherein the solvent for the reaction is selected from mixed solvents of dichloromethane and methanol;
the volume ratio of the dichloromethane to the methanol is (1-4): 1.
6. The method for producing a cyclometallated iridium complex having anti-inflammatory and antitumor activities according to claim 3, wherein the temperature of the reaction is 40 to 55 ℃.
7. The method for preparing a cyclometallated iridium complex having anti-inflammatory and antitumor activities according to claim 3, wherein the reaction further comprises the following steps after completion:
and adding a saturated ammonium hexafluorophosphate solution into the reaction system, removing the solvent after the reaction is finished, and adding the rest reaction solution into diethyl ether to separate out solid precipitate to obtain the cyclometallated iridium complex.
8. Use of a cyclometalated iridium complex with anti-inflammatory and anti-tumor activity as claimed in any one of claims 1 to 2 for the preparation of anti-tumor and anti-inflammatory drugs.
9. The use according to claim 8, wherein the anti-tumor is an anti-solid tumor; the solid tumor is cervical cancer cell.
10. The use according to claim 8, wherein the anti-inflammatory inflammation is an inflammatory response induced by LPS in RAW264.7 cells.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310359647.2A CN116425804B (en) | 2023-04-04 | 2023-04-04 | Cyclometalated iridium complex with anti-inflammatory and anti-tumor activities and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310359647.2A CN116425804B (en) | 2023-04-04 | 2023-04-04 | Cyclometalated iridium complex with anti-inflammatory and anti-tumor activities and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116425804A true CN116425804A (en) | 2023-07-14 |
| CN116425804B CN116425804B (en) | 2023-09-29 |
Family
ID=87086699
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310359647.2A Active CN116425804B (en) | 2023-04-04 | 2023-04-04 | Cyclometalated iridium complex with anti-inflammatory and anti-tumor activities and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116425804B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170102331A1 (en) * | 2015-10-12 | 2017-04-13 | Hong Kong Baptist University | Luminescent Iridium(III) complex and its uses thereof for the G-quadruplex-based switch-on rapid detection of lead ions |
| US20170145472A1 (en) * | 2015-11-24 | 2017-05-25 | Hong Kong Baptist University | Method of detecting helicase activity |
| CN107793455A (en) * | 2017-09-27 | 2018-03-13 | 广东医科大学 | A kind of ring iridium (III) metal complex and its preparation method and application |
| CN108635357A (en) * | 2018-05-24 | 2018-10-12 | 广东药科大学 | A kind of application of complex of iridium in preparing mitochondria anti-tumor drugs targeting |
| CN111732610A (en) * | 2020-07-06 | 2020-10-02 | 广东医科大学 | Cyclometalated iridium complex with anti-tumor and antibacterial activities and preparation method and application thereof |
| CN113512072A (en) * | 2021-07-20 | 2021-10-19 | 广州市第一人民医院（广州消化疾病中心、广州医科大学附属市一人民医院、华南理工大学附属第二医院） | Metal iridium (III) complex and preparation method and application thereof |
-
2023
- 2023-04-04 CN CN202310359647.2A patent/CN116425804B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170102331A1 (en) * | 2015-10-12 | 2017-04-13 | Hong Kong Baptist University | Luminescent Iridium(III) complex and its uses thereof for the G-quadruplex-based switch-on rapid detection of lead ions |
| US20170145472A1 (en) * | 2015-11-24 | 2017-05-25 | Hong Kong Baptist University | Method of detecting helicase activity |
| CN107793455A (en) * | 2017-09-27 | 2018-03-13 | 广东医科大学 | A kind of ring iridium (III) metal complex and its preparation method and application |
| CN108635357A (en) * | 2018-05-24 | 2018-10-12 | 广东药科大学 | A kind of application of complex of iridium in preparing mitochondria anti-tumor drugs targeting |
| CN111732610A (en) * | 2020-07-06 | 2020-10-02 | 广东医科大学 | Cyclometalated iridium complex with anti-tumor and antibacterial activities and preparation method and application thereof |
| CN113512072A (en) * | 2021-07-20 | 2021-10-19 | 广州市第一人民医院（广州消化疾病中心、广州医科大学附属市一人民医院、华南理工大学附属第二医院） | Metal iridium (III) complex and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| MARION GRAF: "Photophysical and biological characterization of new cationic cyclometalated M(III) complexes of rhodium and iridium", 《JOURNAL OF ORGANOMETALLIC CHEMISTRY》, pages 46 - 52 * |
| SHENG LIN等，: "Luminescence switch-on detection of protein tyrosine kinase-7 using a G-quadruplex-selective probe†", 《CHEM. SCI.》, pages 4284 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116425804B (en) | 2023-09-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111559991B (en) | Preparation method and application of naphthylamine compound and salt thereof | |
| CN113234116B (en) | Tripterine derivative, preparation method and medical application thereof | |
| CN112656795A (en) | Action mechanism and application of fangchinoline in resisting tuberculosis membrane melanoma | |
| CN113845551B (en) | Pt (II) complex with photodynamic anti-triple-negative breast cancer activity and preparation method and application thereof | |
| CN116425804B (en) | Cyclometalated iridium complex with anti-inflammatory and anti-tumor activities and preparation method and application thereof | |
| CN111072725B (en) | Compound with naproxen tetravalent platinum structure, preparation method and application thereof in preparation of antitumor drugs | |
| CN108553455B (en) | Application of trialdehyde phloroglucinol thiosemicarbazone heterozygote compound in antitumor drugs | |
| CN110923324A (en) | Breast cancer miRNA marker and application thereof | |
| CN111388475B (en) | Application of SETD inhibitor in anti-tumor drug resistance and drug containing SETD inhibitor | |
| CN111269253B (en) | Chalcone Sanjunolide derivative and application thereof in preparation of castration-resistant prostate cancer drugs | |
| CN104830775B (en) | A kind of triple negative breast cancer cisplatin-resistant cell strain and its preparation method and application | |
| CN110698512B (en) | Tin complex with 2-acetylpyridine thiosemicarbazone as ligand and synthesis method thereof | |
| CN113121370A (en) | Hexadecylaminobutanetriol compound, synthetic method and application thereof in anti-tumor and anti-fungal aspects | |
| CN106883271B (en) | ONS tridentate ligand Pt (II) complex with antitumor activity as well as preparation method and application thereof | |
| CN112791081A (en) | Application of white ketone in preparation of lung cancer treatment medicine | |
| CN109232662B (en) | Compound with anti-tumor effect and preparation method and application thereof | |
| CN110964056A (en) | Preparation method and application of fluorine-containing aromatic ring carboxylic acid tetramer compound | |
| CN109438525B (en) | Compound with chemotherapy and phototherapy antitumor effects and preparation method and application thereof | |
| CN113387985B (en) | Iridium complex and application thereof in inhibition of lung cancer drug-resistant strains | |
| CN110882265B (en) | New application of Lonicera macranthoides saponin B | |
| CN110964054A (en) | Preparation method and application of aromatic carboxylic ester compound | |
| CN109172553B (en) | Application of erythrina indica glycoside A1 in preparing medicine for treating human colon cancer | |
| CN108721260B (en) | Application of erythrina indica glycoside A1 in preparing medicine for treating human liver cancer | |
| CN113069451B (en) | Preparation method of pyrrole-2-sulfonamide compound and application of pyrrole-2-sulfonamide compound in preparation of antitumor drugs | |
| CN110128333B (en) | Cu metal complex and synthetic method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |