CN110713500A - Palladium complex using 2-benzoylpyridine thiosemicarbazone and synthetic method thereof - Google Patents
Palladium complex using 2-benzoylpyridine thiosemicarbazone and synthetic method thereof Download PDFInfo
- Publication number
- CN110713500A CN110713500A CN201911117741.7A CN201911117741A CN110713500A CN 110713500 A CN110713500 A CN 110713500A CN 201911117741 A CN201911117741 A CN 201911117741A CN 110713500 A CN110713500 A CN 110713500A
- Authority
- CN
- China
- Prior art keywords
- palladium complex
- ligand
- benzoylpyridine
- mixing
- 3mmol
- 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
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 title claims abstract description 72
- 229910052763 palladium Inorganic materials 0.000 title claims abstract description 37
- DJSSWOPZTQTBBW-FOWTUZBSSA-N [(e)-[phenyl(pyridin-2-yl)methylidene]amino]thiourea Chemical compound C=1C=CC=NC=1C(=N/NC(=S)N)/C1=CC=CC=C1 DJSSWOPZTQTBBW-FOWTUZBSSA-N 0.000 title claims description 10
- 238000010189 synthetic method Methods 0.000 title description 2
- 239000003446 ligand Substances 0.000 claims abstract description 25
- 238000002156 mixing Methods 0.000 claims abstract description 13
- GCSHUYKULREZSJ-UHFFFAOYSA-N phenyl(pyridin-2-yl)methanone Chemical compound C=1C=CC=NC=1C(=O)C1=CC=CC=C1 GCSHUYKULREZSJ-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000001308 synthesis method Methods 0.000 claims abstract description 7
- FCPHVJQWZFNNKD-UHFFFAOYSA-N 3-amino-1,1-dimethylthiourea Chemical compound CN(C)C(=S)NN FCPHVJQWZFNNKD-UHFFFAOYSA-N 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- 239000002244 precipitate Substances 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 239000013078 crystal Substances 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 101150003085 Pdcl gene Proteins 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 239000011521 glass Substances 0.000 claims description 6
- 239000003208 petroleum Substances 0.000 claims description 6
- 238000007789 sealing Methods 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 238000010898 silica gel chromatography Methods 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 238000007605 air drying Methods 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 3
- 230000000694 effects Effects 0.000 abstract description 16
- 230000005764 inhibitory process Effects 0.000 abstract description 9
- 238000002474 experimental method Methods 0.000 abstract description 6
- 239000002246 antineoplastic agent Substances 0.000 abstract description 5
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 5
- 238000000338 in vitro Methods 0.000 abstract description 5
- 150000002940 palladium Chemical class 0.000 abstract description 5
- 238000006243 chemical reaction Methods 0.000 abstract description 3
- 230000035755 proliferation Effects 0.000 abstract description 3
- SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 abstract description 3
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- 229910002666 PdCl2 Inorganic materials 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 125000003118 aryl group Chemical group 0.000 description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 229960004316 cisplatin Drugs 0.000 description 5
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 5
- -1 thiosemicarbazone Schiff base compound Chemical class 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- 239000002262 Schiff base Substances 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000005918 in vitro anti-tumor Effects 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 208000027831 neuroepithelial neoplasm Diseases 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000002941 palladium compounds Chemical class 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 201000011549 stomach cancer Diseases 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
- 238000003786 synthesis reaction Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- BXSSCSKCOFKPOK-ARGVQFGUSA-N (2s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-amino-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3- Chemical compound C([C@@H](C(=O)N[C@@H](CCCC)C(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C(C)C)C1=CC=CC=C1 BXSSCSKCOFKPOK-ARGVQFGUSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000002365 anti-tubercular Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000000006 cell growth inhibition assay Methods 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 229940042396 direct acting antivirals thiosemicarbazones Drugs 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical class [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003876 thiosemicarbazone group Chemical group 0.000 description 1
- 230000004565 tumor cell growth 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
- C07F15/006—Palladium compounds
- C07F15/0066—Palladium compounds without a metal-carbon linkage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a palladium complex of thiosemicarbazone by 2-benzoylpyridine and a synthesis method thereof, wherein the synthesis method comprises the steps of mixing and reacting 2-benzoylpyridine with 4, 4-dimethyl-3-thiosemicarbazide and 3-pyrrole-3-thiosemicarbazide respectively to prepare a ligand; taking the prepared ligand and PdCl2The reaction gave palladium complexes C1 and C2. The invention further performs in vitro proliferation inhibition activity experiments on the synthesized palladium complex C1-C2, and the results show that the synthesized palladium complex has generally good in vitro activity, shows good inhibition activity, has little toxic effect on normal cells of human, and is suitable for preparing high-efficiency and low-toxicity antitumor drugs.
Description
Technical Field
The invention relates to a palladium complex, in particular to a palladium complex using 2-benzoylpyridine thiosemicarbazone and a synthesis method thereof.
Background
Cisplatin has been the driving force for the design of similar platinum drugs for the treatment of cancer since its introduction in medical practice in the 70's of the 20 th century. However, extensive research over the past few decades has provided undisputed evidence for the adverse side effects of cisplatin and other platinum-based anti-cancer drugs such as carboplatin and oxaliplatin, accelerating the search for and development of alternative therapies.
In recent years, due to the similarity of coordination chemical properties of palladium (II) complexes and platinum (II), a new antitumor drug is tried to be researched on the basis of the coordination chemical properties, so that the platinum antitumor drug is replaced, and the palladium complexes have better in-vitro anticancer and apoptosis induction activities than cisplatin and lower toxicity to normal cells.
The thiosemicarbazone Schiff base compound and the complex thereof have biological activities in various aspects such as antibiosis, antivirus, antituberculosis, anticancer and the like, so that the thiosemicarbazone Schiff base compound and the complex thereof are widely concerned in biological, chemical and medical fields of various countries in the world. The heterocyclic thiosemicarbazone compound and the metal complex thereof become hot spots of research in recent years due to more remarkable biological activity.
We have combined palladium complexes with 2-benzoylpyridine thiosemicarbazone ligands and studied their antitumor activity.
Disclosure of Invention
The invention aims to provide a palladium complex with 2-benzoylpyridine thiosemicarbazone ligand and a synthesis method thereof.
The technical scheme for realizing the purpose of the invention is as follows:
a palladium complex with 2-benzoylpyridine thiosemicarbazone ligand, having the formula C1-C2:
the synthetic route of the palladium compound shown by C1-C2 is as follows:
the synthesis method of the palladium complex C1 comprises the following steps:
(1) mixing 3mmol of 2-benzoylpyridine and 3mmol of 4, 4-dimethyl-3-thiosemicarbazide, dissolving in 20ml of methanol after mixing, dropwise adding 500ul of concentrated sulfuric acid, and stirring and reacting at 65 ℃ for 6 hours to obtain a light yellow precipitate; filtering the precipitate, washing with saturated sodium bicarbonate and water successively, separating with silica gel column chromatography, eluting with petroleum ether and ethyl acetate 10:1, and drying to obtain ligand L1;
(2) 0.05mmol of ligand L1 and 0.05mmol of PdCl were weighed out2Placing the mixture into a glass tube with one sealed end, dropwise adding 1mL of LEOH and 1mL of EtOH for dissolution, and vacuumizing and sealing the mixture; standing for 72h in a 60 ℃ forced air drying oven, taking out, and slowly cooling to room temperature to obtain an orange crystal, namely the target palladium complex C1.
The synthesis method of the palladium complex C2 comprises the following steps:
(1) mixing 3mmol of 2-benzoylpyridine and 3mmol of 3-pyrrole-3-thiosemicarbazide, dissolving in 20ml of methanol after mixing, dropwise adding 500uL of concentrated sulfuric acid, and stirring and reacting at 65 ℃ for 6 hours to obtain a light yellow precipitate; filtering the precipitate, washing with saturated sodium bicarbonate and water successively, separating with silica gel column chromatography, eluting with petroleum ether and ethyl acetate 10:1, and drying to obtain ligand L2;
(2) 0.05mmol of ligand L2 and 0.05mmol of PdCl were weighed out2Placing the mixture into a glass tube with one sealed end, and dropwise adding 1mL of MoLEOH and 1mL of CH3COCH3Dissolving, vacuumizing and sealing; and (3) standing for 72h in a 60 ℃ forced air drying oven, taking out, and slowly cooling to room temperature to obtain an orange crystal, namely the target palladium complex C2.
The invention selects 2-benzoylpyridine and thiosemicarbazide to carry out condensation reaction to obtain a ligand, the ligand further comprises a synthetic palladium compound C1-C2 which is subjected to an in vitro anti-tumor activity test, and the ligand proves that the activity of the pure 2-benzoylpyridine thiosemicarbazone is not high for cancer cells, and the activity is relatively improved after the ligand is coordinated with palladium ions.
Compared with the prior art: the invention uses 2-benzoylpyridine thiosemicarbazone to react with palladium, the thiosemicarbazone is an important universal ligand, and sulfur is crucial in metal-ligand bonding due to potential electron donating capability. In particular, compounds in which the thiosemicarbazone side chain is attached to the heterocycle in the alpha position, i.e. alpha-N-heterocyclic thiosemicarbazones (N-TSCs), are strong metal chelators, some of which have anti-tumor activity themselves. Thus, we constructed alpha-azabicyclo (thiosemicarbazone) palladium complexes containing dihydropyridines.
The invention further performs in vitro proliferation inhibition activity experiments on the synthesized palladium complex C1-C2, and the results show that the synthesized palladium complex has generally good in vitro activity, shows good inhibition activity, has little toxic effect on normal cells of human, and is suitable for preparing high-efficiency and low-toxicity antitumor drugs.
Drawings
FIG. 1 is a single crystal structural diagram of a C1 palladium complex synthesized in example 1.
FIG. 2 is a single crystal structural diagram of a C2 palladium complex synthesized in example 2.
Detailed Description
The present disclosure will be better understood from the following detailed description taken in conjunction with the accompanying drawings, which are set forth below, but are not intended to limit the present disclosure to the following embodiments.
Example 1:
the synthesis of palladium complex C1 comprises the following steps:
(1) mixing 3mmol of 2-benzoylpyridine and 3mmol of 4, 4-dimethyl-3-thiosemicarbazide, dissolving in 20ml of methanol after mixing, dropwise adding 500ul of concentrated sulfuric acid, and carrying out reflux stirring reaction at 65 ℃ for 6 hours to obtain a light yellow precipitate; filtering the precipitate, washing with saturated sodium bicarbonate and water successively, eluting with petroleum ether and ethyl acetate in the ratio of 10 to 1, and drying to obtain ligand L1 in the yield: 82%;
elemental analysis, anal.Calcd (%) for C15H16N4S:C,63.35；H,5,67；N,19.70；S,11.28.Found:C,63.28；H,5.11；N,18.75；S,11.14；
Infrared spectrum, IR, cm-1:3463(s,amide),3274(s,NH),3208(m,aromatic hydrogen),1526(s),1495(s),1463(s,aromatic),1287(m,C＝N),1079(s,thioamide),934(m,C-H),757(m,C＝S),694(m)；
Mass Spectrometry, ESI + m/z: C15H16N4S,284.11[M+H]+；
(2) 0.05mmol of ligand L1 and 0.05mmol of PdCl were weighed out2Placing in a glass tube with one sealed end, and dropwise adding 1mLCH3OH and 1mL CH3CH2Dissolving OH, and vacuumizing and sealing; standing for 72h in a 60 ℃ blast drying oven, taking out, and slowly cooling to room temperature to obtain an orange crystal, namely the target palladium complex C1 with the yield of 69%;
elemental analysis, anal.Calcd (%) for C15H15ClN4PdS:C,42.37；H,3.56；N,13.18；S,7.54.Found:C,42.85；H,3.57；N,12.97；S,7.94；
Infrared spectrum, IR, cm-1:3319(s,amide),3268(s,NH),3059(m,aromatic hydrogen),1541(s),1501(s),1429(s,aromatic),1338(m,C＝N),1133s,thioamide),901(m,C-H),778(m,C＝S),687(m)；
Mass Spectrometry, ESI + m/z: C19H15ClN4PdS,425.97[M-H]+。
Example 2:
the synthesis of palladium complex C2 comprises the following steps:
(1) mixing 3mmol of 2-benzoylpyridine and 3mmol of 3-pyrrole-3-thiosemicarbazide, dissolving in 20ml of methanol after mixing, dropwise adding 500uL of concentrated sulfuric acid, and carrying out reflux stirring reaction at 65 ℃ for 6 hours to obtain a light yellow precipitate; filtering the precipitate, washing the precipitate with saturated sodium bicarbonate and water successively, separating the precipitate with silica gel column chromatography, eluting with petroleum ether and ethyl acetate in the ratio of 10 to 1, and drying to obtain ligand L2 in the yield: 85 percent;
elemental analysis, anal.Calcd (%) for C17H18N4S:C,65.78；H,5.84；N,18.05；S,10.33.Found:C,65.55；H,5.59；N,18.27；S,10.04；
Infrared spectrum, IR, cm-1:3355(s,amide),3249(s,NH),3057(m,aromatic hydrogen),1585(s),1469(s),1438(s,aromatic),1236(m,C＝N),1154(s,thioamide),895(m,C-H),797(m,C＝S),695(m)；
Mass Spectrometry, ESI + m/z: C17H18N4S,310.11[M+Na]；
(2) 0.05mmol of ligand L2 and 0.05mmol of PdCl were weighed out2Placed in a glass tube sealed at one endDropwise addition of 1mLCH3OH and 1mL CH3COCH3Dissolving, vacuumizing and sealing; standing for 72h in a 60 ℃ blast drying oven, taking out, and slowly cooling to room temperature to obtain an orange crystal, namely the target palladium complex C2, with the yield of 70%;
elemental analysis, anal.Calcd (%) for C17H17ClN4PdS:C,45.24；H,3.80；N,7.86；S,12.42.Found:C,45.27；H,3.72；N,7.76；S,12.32；
Infrared spectrum, IR, cm-1:3764(s,amide),3440(s,NH),2973(m,aromatic hydrogen),1637(s),1532(s),1437(s,aromatic),1295(m,C＝N),1155(s,thioamide),930(m,C-H),703(m,C＝S),644(m)；
Mass Spectrometry, ESI + m/z: C17H17ClN4PdS,451.98[M-H]+。
To illustrate the palladium complexes of the present invention, the applicants conducted in vitro antitumor activity experiments on the complexes C1-C2 prepared in the above examples 1-2:
proliferation inhibition activity experiments were performed on human neuroepithelial tumor cells (SK-N-MC), human cervical cancer cells (Hela), human glioma cells (U87-MG), human gastric cancer cells (MGC-803), and human normal liver cells (HL-7702):
1. cell lines and cell cultures
Human cell strains such as human neuroepithelial tumor cells, human cervical cancer cells, human glioma cells, human gastric cancer cells, human liver cancer cells, human normal liver cells and the like are selected for the experiment.
All cell lines were cultured in RPMI-1640/DMEM/MEM medium containing 10% calf serum and 100U/mL streptomycin, and cultured in a 5% by volume CO 2-containing incubator at 37 ℃. Taking the five cells out of a freezer at the temperature of-140 ℃, unfreezing the five cells in a constant-temperature water bath kettle at the temperature of 37 ℃, transferring the five cells into five sterilized culture bottles filled with 10mL of culture solution, marking the culture bottles, putting the culture bottles into a 37 ℃ and 5% CO2 culture box, changing the culture solution after attaching the cells to the wall, when the cell amount in the culture bottles reaches 80% -90%, carrying out passage on the cells, carrying out digestion and flask culture on the cells, and freezing and storing the cells in the freezer at the temperature of-140 ℃ after the experiment is completed.
2. Preparation of test Compounds
The purity of the used test drug is more than or equal to 95 percent, the DMSO stock solution is diluted by physiological buffer solution to be prepared into 5mmol/L final solution, wherein the concentration of the cosolvent DMSO is less than or equal to 1 percent, and the degree of inhibition of the compound on the growth of various tumor cells under the concentration is tested.
3. Cell growth inhibition assay (MTT method)
(1) Digesting the cells to obtain cell suspension, counting the cells, placing a proper amount of cells in a sample adding groove, adding culture medium to dilute the cells until the cell concentration reaches 6 x 104cells/mL, in each well 180 u L inoculated in 96 hole culture plate, to test the cell concentration to each well 1000 ~ 10000/hole (the marginal hole with 200 u L sterile PBS filled);
(2) incubating for 24h at 37 ℃ with 5% CO2 until cell monolayers are fully paved on the bottom of the wells, adding 20 μ L of medicine with a certain concentration gradient into each well, and arranging 5 multiple wells for each concentration gradient;
(3) incubating for 48h at 37 ℃ with 5% CO2, and observing under an inverted microscope;
(4) add 10. mu.L of MTT solution (5mg/mL PBS, i.e., 0.5% MTT) to each well and continue culturing for 5 h;
(5) terminating the culture, carefully removing the culture solution in the wells, adding 100. mu.L of DMSO into each well to sufficiently dissolve formazan precipitate, shaking for 10min, and measuring the optical density of each well at a wavelength of 570nm and a reference wavelength of 450nm in a microplate reader;
(6) simultaneously, a zero setting hole (culture medium, MTT, DMSO) and a control hole (cells, a drug dissolving medium with the same concentration, a culture solution, MTT, DMSO) are arranged.
(7) The number of living cells was judged from the measured optical density values (OD values), and the larger the OD value, the stronger the cell activity. Using the formula:
tumor cell growth inhibition (%) [ (1-mean OD of experimental group)/(mean OD of control group) ] ×%;
IC50 determination: using the above method, each complex was subjected to a concentration gradient of 6 concentrations, including 1 blank, and 5 secondary wells were also provided for each concentration, and the inhibition was experimentally obtained for each different concentration, and the IC50 values for the compounds were calculated in SPSS software.
Table 1: IC of ligands and complexes on different cell lines50Lower values (μ M) indicate better inhibition of cancer cells by the complex.
The experimental results show that: for the 5 cancer cells, the activity of the pure 2-benzoylpyridine thiosemicarbazone ligand is not high, and is relatively improved after being coordinated with palladium ions, the activity of the C1 palladium complex is higher and is probably related to lipophilic groups on the ligand, so that the activity is increased, and in general, the activity of the palladium complex is better than that of cisplatin and the toxicity of the palladium complex is lower than that of cisplatin.
Claims (4)
1. A palladium complex of 2-benzoylpyridine thiosemicarbazone, characterized in that the palladium complex has the formula C1-C2:
2. the palladium complex of claim 1, wherein: the synthetic route of the palladium complex shown by C1-C2 is as follows:
3. the method for synthesizing the palladium complex as claimed in claim 2, wherein the method for synthesizing the palladium complex C1 comprises the following steps:
(1) mixing 3mmol of 2-benzoylpyridine and 3mmol of 4, 4-dimethyl-3-thiosemicarbazide, dissolving in 20ml of methanol after mixing, dropwise adding 500ul of concentrated sulfuric acid, and stirring and reacting at 65 ℃ for 6 hours to obtain a light yellow precipitate; filtering the precipitate, washing with saturated sodium bicarbonate and water successively, separating with silica gel column chromatography, eluting with petroleum ether and ethyl acetate 10:1, and drying to obtain ligand L1;
(2) 0.05mmol of ligand L1 and 0.05mmol of PdCl were weighed out2Placing the mixture into a glass tube with one sealed end, dropwise adding 1mL of MeOH and 1mL of EtOH for dissolution, and vacuumizing and sealing the mixture; standing for 72h in a 60 ℃ forced air drying oven, taking out, and slowly cooling to room temperature to obtain an orange crystal, namely the target palladium complex C1.
4. The method for synthesizing a palladium complex according to claim 2, characterized in that: the synthesis method of the palladium complex C2 comprises the following steps:
(1) mixing 3mmol of 2-benzoylpyridine and 3mmol of 3-pyrrole-3-thiosemicarbazide, dissolving in 20ml of methanol after mixing, dropwise adding 500uL of concentrated sulfuric acid, and stirring and reacting at 65 ℃ for 6 hours to obtain a light yellow precipitate; filtering the precipitate, washing with saturated sodium bicarbonate and water successively, separating with silica gel column chromatography, eluting with petroleum ether and ethyl acetate 10:1, and drying to obtain ligand L2;
(2) 0.05mmol of ligand L2 and 0.05mmol of PdCl were weighed out2Put into a glass tube sealed at one end, and 1mL MeOH and 1mL CH are added dropwise3COCH3Dissolving, vacuumizing and sealing; standing for 72h in a 60 ℃ forced air drying oven, taking out, and slowly cooling to room temperature to obtain an orange crystal, namely the target palladium complex C2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911117741.7A CN110713500B (en) | 2019-11-15 | 2019-11-15 | Palladium complex using 2-benzoylpyridine thiosemicarbazone and synthetic method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911117741.7A CN110713500B (en) | 2019-11-15 | 2019-11-15 | Palladium complex using 2-benzoylpyridine thiosemicarbazone and synthetic method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110713500A true CN110713500A (en) | 2020-01-21 |
| CN110713500B CN110713500B (en) | 2021-09-14 |
Family
ID=69216080
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911117741.7A Expired - Fee Related CN110713500B (en) | 2019-11-15 | 2019-11-15 | Palladium complex using 2-benzoylpyridine thiosemicarbazone and synthetic method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110713500B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111233837A (en) * | 2020-02-05 | 2020-06-05 | 李本 | Thiosemicarbazone compound and preparation method and application thereof |
| CN111925398A (en) * | 2020-09-22 | 2020-11-13 | 广西师范大学 | FTO (fluorine-doped tin oxide) small-molecule inhibitor palladium complex and synthesis method thereof |
| CN112028911A (en) * | 2020-09-22 | 2020-12-04 | 广西师范大学 | Zinc complex taking 2-benzoylpyridine thiosemicarbazone as ligand and synthetic method and application thereof |
| CN112062789A (en) * | 2020-09-22 | 2020-12-11 | 广西师范大学 | Palladium complex taking 2-acetylpyridine thiosemicarbazone as ligand and synthetic method thereof |
| CN112079877A (en) * | 2020-09-22 | 2020-12-15 | 广西师范大学 | Platinum complex with 2-benzoylpyridine thiosemicarbazone as ligand and synthetic method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104844631A (en) * | 2015-05-15 | 2015-08-19 | 广西师范大学 | Copper metal complex and compound prepared from copper metal complex and human serum albumin as well as synthesis method and application thereof |
| CN109897071A (en) * | 2019-03-28 | 2019-06-18 | 广西师范大学 | It is a kind of using 2- pyridine carboxaldehyde thiosemicarbazones as the platinum complex of ligand and its synthetic method and application |
-
2019
- 2019-11-15 CN CN201911117741.7A patent/CN110713500B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104844631A (en) * | 2015-05-15 | 2015-08-19 | 广西师范大学 | Copper metal complex and compound prepared from copper metal complex and human serum albumin as well as synthesis method and application thereof |
| CN109897071A (en) * | 2019-03-28 | 2019-06-18 | 广西师范大学 | It is a kind of using 2- pyridine carboxaldehyde thiosemicarbazones as the platinum complex of ligand and its synthetic method and application |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111233837A (en) * | 2020-02-05 | 2020-06-05 | 李本 | Thiosemicarbazone compound and preparation method and application thereof |
| CN111925398A (en) * | 2020-09-22 | 2020-11-13 | 广西师范大学 | FTO (fluorine-doped tin oxide) small-molecule inhibitor palladium complex and synthesis method thereof |
| CN112028911A (en) * | 2020-09-22 | 2020-12-04 | 广西师范大学 | Zinc complex taking 2-benzoylpyridine thiosemicarbazone as ligand and synthetic method and application thereof |
| CN112062789A (en) * | 2020-09-22 | 2020-12-11 | 广西师范大学 | Palladium complex taking 2-acetylpyridine thiosemicarbazone as ligand and synthetic method thereof |
| CN112079877A (en) * | 2020-09-22 | 2020-12-15 | 广西师范大学 | Platinum complex with 2-benzoylpyridine thiosemicarbazone as ligand and synthetic method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110713500B (en) | 2021-09-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110713500B (en) | Palladium complex using 2-benzoylpyridine thiosemicarbazone and synthetic method thereof | |
| CN107629089B (en) | Tacrine-platinum (II) complex and its synthetic method of high activity and application | |
| CN107955042B (en) | Platinum complex with anticancer activity, preparation method and application | |
| CN111393483B (en) | Tetravalent platinum naphthalimide complex, preparation method and application thereof | |
| CN109796497B (en) | Bismuth compound with 2-acetyl-3-ethylpyrazine thiosemicarbazone as ligand and synthesis method thereof | |
| CN109908364B (en) | Synthetic method and application of gold (III) metal complex with human serum albumin as carrier | |
| CN111205311A (en) | Novel high-antitumor-activity white leaf vine zinc (II) complex and synthesis method and application thereof | |
| CN109810128B (en) | Indium complex with 2-pyridylaldehyde thiosemicarbazone as ligand and synthetic method and application thereof | |
| CN111377975A (en) | Novel mitochondrion-targeted iridium complex and preparation method and application thereof | |
| CN110372754A (en) | A kind of novel metal complex of iridium and its preparation method and application | |
| CN111072725B (en) | Compound with naproxen tetravalent platinum structure, preparation method and application thereof in preparation of antitumor drugs | |
| CN106632424B (en) | Using 1- (2- pyridines) -9- benzyls-B-carboline as the chlorination copper complex and its synthetic method of ligand and application | |
| CN108530436B (en) | Pyrazole compound and preparation method and application thereof | |
| CN107827934B (en) | Tetravalent platinum complex with anticancer activity, preparation method and application | |
| CN106554362B (en) | It is a kind of using 1- pyridines-B-carboline as copper chloride (II) chelate and its synthetic method of ligand and application | |
| CN106565755B (en) | Using 1- pyridine -6- methoxy-p-carbolines as copper nitrate (II) chelate and its synthetic method of ligand and application | |
| CN106632420B (en) | Using 1- (2- pyridines) -9- butyl-ss-carbolines as the chlorination copper complex and its synthetic method of ligand and application | |
| CN110698512B (en) | Tin complex with 2-acetylpyridine thiosemicarbazone as ligand and synthesis method thereof | |
| CN113880872A (en) | Preparation of camptothecin boric acid compound and application of camptothecin boric acid compound in anti-tumor aspect | |
| CN113735781A (en) | Copper complex and preparation method and application thereof | |
| CN110128452B (en) | Gold complex and synthesis method and application thereof | |
| CN114805404B (en) | Metal complex based on dehydroabietylamine and preparation method and application thereof | |
| CN112079853A (en) | Zinc complex with 2-pyridylaldehyde thiosemicarbazone as ligand and synthetic method and application thereof | |
| CN106478687B (en) | Using 1- (2- pyridines) -9- ethyl-beta-carbolines as the chlorination copper complex and its synthetic method of ligand and application | |
| CN112079851B (en) | Gold complex of FTO (fluorine-doped tin oxide) small-molecule inhibitor and synthetic method 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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20210914 |