New triorganotin(iv) compounds with aromatic carboxylate ligands: synthesis and evaluation of the pro-apoptotic mechanism.

Three new organotin(iv) carboxylate compounds were synthesized and structurally characterized by elemental analysis and FT-IR and multinuclear NMR (H, C, Sn) spectroscopy. Single X-ray crystallography reveals that compound C2 has a monoclinic crystal system with space group 2/ having distorted bipyramidal geometry defined by CSnO. The synthesized compounds were screened for drug-DNA interactions UV-Vis spectroscopy and cyclic voltammetry showing good activity with high binding constants. Theoretical investigations also support the reactivity of the compounds as depicted from natural bond orbital (NBO) analysis using Gaussian 09. Synthesized compounds were initially evaluated on two cancer (HeLa and MCF-7) cell lines and cytotoxicity to normal cells was evaluated using a non-cancerous (BHK-21) cell line. All the compounds were found to be active, with IC values less than that of the standard drug cisplatin. The cytotoxic effect of the most potent compound C2 was confirmed by LDH cytotoxicity assay and fluorescence imaging after PI staining. Apoptotic features in compound C2 treated cancer cells were visualized after DAPI staining while regulation of apoptosis was observed by reactive oxygen species generation, binding of C2 with DNA, a change in mitochondrial membrane potential and expression of activated caspase-9 and caspase-3 in cancer cells. Results are indicative of activation of the intrinsic pathway of apoptosis in C2 treated cancer cells.