Antiproliferative activity and DNA binding studies of cyclometalated complexes of platinum(II) containing 2-vinylpyridine

The cytotoxic activity of four cyclometalated platinum(II) complexes [PtMe(vpy)(L)], containing 2-vinylpyridine (vpy) and the phosphine ligands (L) PMe2Ph (1a), PPh3 (1b), PMePh2 (1c), and P(c-Hex)(3) (1d), were evaluated against human breast cancer (MDA-MB-231), human lung cancer (A549), human colon cancer (SW1116), and non-tumor epithelial breast (MCF-10 A) cell lines. The highest activity was found for 1c with IC50 values of 21.10 mu M, 23.36 mu M, and 12.96 mu M, compared to cisplatin, which was 10.12 mu M, 47.57 mu M, and 19.50 mu M against the A549, SW1116, and MDA-MB-231 cell lines, respectively. 1a-d showed a higher selectivity index (SI) than cisplatin. Docking studies confirmed interaction to the DNA minor groove for all complexes. Genotoxicity studies on 1c showed interactions with the genomic content of malignant cells. Compared with cisplatin as a positive control, a slight shift was found in the electrophoresis mobility, which was utilized further to study the direct interaction of 1c with DNA. [GRAPHICS] .