Triorganotin (IV) carboxylates as potential anticancer agents: Their synthesis, physiochemical characterization, and cytotoxic activity against HeLa and MCF‐7 cancer cells

Abstract

Three triorganotin (IV) cyclopentane carboxylates were synthesized and structurally characterized by in solid state by Fourier‐transform infrared spectroscopy and single crystal diffraction, and in solution by NMR (1H, 13C, and 119Sn) spectroscopy. The complexes were tested for their anticancer activity against MCF‐7 and HeLa cells along with normal BHK‐21 cells. As revealed by MTT assay, complex 2 was identified as the most potent derivative with an IC50 value of 2.59 and 0.051 μM against HeLa and MCF‐7 cells, respectively. The results were compared with cisplatin as reference drug. Fluorescent microscopic studies using 4′,6‐diamidino‐2‐phenylindole (DAPI) and propidium iodide (PI) staining confirmed the occurrence of apoptosis in HeLa cells treated with the most active complex 2. The complex 2 also triggered the release of lactate dehydrogenase (LDH) in treated HeLa and MCF‐7 cells whereas a luminescence assay displayed a remarkable increase in the activity of caspase‐9 and ‐3. Moreover, flow cytometric results revealed that complex 2 caused G0/G1 arrest in the treated HeLa cells. The complexes were further screened for DNA binding studies through UV‐vis spectroscopy and cyclic voltammetry. The high activity of complex 2 was attributed to its higher Lewis acidity as indicated by natural bond orbital (NBO) analysis. Theoretical modelling and molecular docking studies were also conducted to study the reactivity of complexes against VEGFR 2 Kinase.