Triphenyltin(IV) compounds bearing modulated azo-carboxylato ligands: Synthesis, structural characterization, in vitro cytotoxicity, BSA/DNA binding affinity, and in silico studies

Abstract

Three novel triphenyltin(IV) compounds with modulated azo-carboxylato ligands: triphenylstannyl (E)-4-((2-hydroxynaphthalen-1-yl)diazenyl)benzoate, 1, triphenylstannyl (E)-4-((4-hydroxyphenyl)diazenyl)benzoate, 2, and triphenylstannyl (E)-4-((4-(dimethylamino)phenyl)diazenyl)benzoate, 3, were synthesized and characterized by elemental analysis, FTIR and NMR (1H, 13C, 119Sn) spectroscopy. The structures and spectra of compounds were predicted by Density Functional Theory (DFT) methods at B3LYP-D3BJ/6–311++G(d,p)(H,C,N,O)/LanL2DZ(Sn) level of theory. Furthermore, the antitumor potential of ligand precursors, HL1–HL3, and appropriate organotin(IV) compounds 1–3 was evaluated across mouse melanoma B16F1, human breast adenocarcinoma MCF-7, human colorectal HT-29 and human prostate PC3 cell lines using MTT and CV assays. The organotin(IV) compounds exhibit enhanced cellular uptake and efficacy in reducing viable cell numbers when compared to free acids. Specifically, compound 3 demonstrates a notable impact at lower nanomolar concentrations on all tested cell lines. Moreover, 3 induces cell death in MCF-7 cells by inhibiting cell division and promoting the overproduction of cellular nitric oxide (NO), ultimately leading to caspase-independent apoptosis. Importantly, this process occurs without concurrent activation of autophagy or the generation of ROS/RNS species. The binding affinity of 1–3 with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) was investigated by fluorescence spectroscopy and molecular docking simulations, suggesting their capacity to interact with these biomolecules.