title: Synthesis, crystal structures and antitumor activity of two platinum(II) complexes with methyl hydrazinecarbodithioate derivatives of indolin-2-one.
abstract: Two new platinum(II) complexes 7a and 7b with methyl hydrazinecarbodithioate derivatives of indolin-2-one have been prepared and characterized by single-crystal X-ray diffraction, NMR spectroscopy and mass spectrometry. Antiproliferative activity of the two complexes and their ligands 6a and 6b against HCT-116, MCF-7 and MDA-MB-231 cell lines was determined by the MTS assay. Complexes 7a and 7b exhibited stronger antiproliferative activity against three cell lines than compounds 6a and 6b (IC50, 1.89-5.60 versus 6.52-35.13 μM). Moreover, treatment of HCT-116 cells with the complexes resulted in an obvious sub-G1 peak by cell cycle profile analysis, and an increase of cleaved PARP1 and caspases 3, 7, and 9 by immunoblotting analysis. Live cell imaging showed that nucleus shrinkage and condensation started to appear when MCF-7 cells were treated with 7a for 8 h. Fluorescent spectrophotometric analysis revealed that the complexes physically associated with calf thymus DNA. Competitive DNA binding assays uncovered that the complexes non-covalently bind to DNA. Taken together, our results indicated that the two new platinum(II) complexes 7a and 7b non-covalently bind to DNA with high affinity and exhibit cytotoxicity against cancer cells by inducing apoptosis.
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing 100048, PR China.
authors.forename: You-Shan
authors.initials: YS
authors.lastname: Li
authors.affiliation: School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, PR China; Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Peng
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing 100048, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing 100048, PR China. Electronic address: slcao@cnu.edu.cn.
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Cao
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, PR China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Bai
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing 100048, PR China.
authors.forename: Chao-Rui
authors.initials: CR
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing 100048, PR China. Electronic address: wancq@cnu.edu.cn.
authors.forename: Chong-Qing
authors.initials: CQ
authors.lastname: Wan
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing 100048, PR China.
authors.forename: Hao-Jie
authors.initials: HJ
authors.lastname: Yan
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing 100048, PR China.
authors.forename: Pan-Pan
authors.initials: PP
authors.lastname: Ding
authors.affiliation: Department of Chemistry, Capital Normal University, Beijing 100048, PR China.
authors.forename: Zhong-Feng
authors.initials: ZF
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Liao
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, PR China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Meng
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, PR China.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, PR China; Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, PR China. Electronic address: xingzhi.xu@szu.edu.cn.
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Xu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D006834:Hydrazines / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D061986:MCF-7 Cells; D008958:Models, Molecular; D008968:Molecular Conformation; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006834:Hydrazines; D007211:Indoles; D009944:Organoplatinum Compounds; C456900:indolin-2-one; D004247:DNA; C427203:calf thymus DNA
keywords: Antiproliferative activity; Apoptosis; Hydrazinecarbodithioate; Platinum(II) complex; Synthesis