<i>Trans</i>-Pd(II) and Pt(II) saccharinate complexes with<i> S,S</i>-diphenylsulfimide: Synthesis, structures, anticancer evaluation and molecular docking

Novel Pd(II) and Pt(II) saccharinate (sac) complexes with S,S-diphenylsulfimide (Ph2SNH), namely trans-[Pd (sac)2(Ph2SNH)2] and trans-[Pt(sac)2(Ph2SNH)2]& sdot;H2O, were synthesized and characterized using FTIR, ESI-MS, NMR spectroscopies. The structure of the Pd(II) complex was confirmed by X-ray crystallography. In vitro cytotoxicity of both complexes was evaluated against A549 (lung), HT29 (colorectal) and MCF7 (breast) human cancer cell lines using SRB (sulforhodamine B) assay. The results indicated that while the Pd(II) complex has no effect on cancer cell line, the Pt(II) complex displayed significant cytotoxicity against all tested cell lines with IC50 values ranging from 8.6 +/- 0.2 to 15.9 +/- 0.1 mu M, nearly comparable to those of cisplatin. In particular, the Pt (II) complex enhanced the cytotoxic activity more than twofold higher compared to cisplatin against MCF7 cells. Annexin V/PI (propidium iodide), caspase 3/7 and cell cycle studies demonstrated that the Pt(II) complex effectively induced apoptosis in MCF7 cells. The complex exhibited superior ROS (reactive oxygen species) generation, which eventually caused DNA double-strand breaks (DSBs) as evidenced by the gamma H2AX assay. Moreover, the complex induced aggregation and fragmentation of mitochondria. Western blotting showed that the Pt(II) complex significantly upregulated the levels of pro-apoptotic Bax, tumor suppressor p53, and cleaved PARP proteins, while greatly downregulated antiapoptotic Bcl-2 protein, clearly confirming intrinsic apoptosis in MCF7 cells. The affinity of the Pt(II) complex toward DNA and Bcl-2 protein as potential targets was further explored by molecular docking studies. The results offer the anticancer potential of the novel Pt(II) complex for further development as a novel metallodrug.