Synthesis, crystal structures and antitumor activity of two platinum(II) complexes with methyl hydrazinecarbodithioate derivatives of indolin-2-one

• DOI: 10.1016/j.ejmech.2016.12.050
• Publication Date: 2016-12-26T19:31:29Z
• Authors: You-Shan Li; Bin Peng; Li Ma; Sheng-Li Cao; Lu-Lu Bai; Chao-Rui Yang; Chong-Qing Wan; Hao-Jie Yan; Pan-Pan Ding; Zhong-Feng Li; Ji Liao; Ying-Ying Meng; Hai-Long Wang; Jing Li; Xingzhi Xu
• Keywords: Platinum compounds

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.