Antiproliferative activity and human serum albumin binding propensity of [SnMe2Cl2(bu2bpy)]: multi-spectroscopic analysis, atomic force microscopy, and computational studies

Abstract

In this study, the multi-spectroscopic methods (UV-vis, fluorometric, circular dichroism), atomic force microscopy (AFM), cyclic voltammetry, molecular docking, and predictor online software (SwissADME-AdmetSAR) were used to investigate the interaction of complex [SnMe2Cl2(bu2bpy)] with human serum albumin (HSA). The calculated binding constant by UV-vis spectroscopy was about 104 M−1. Also, the polarity around the Trp-214 residue and the hydrophobicity were changed. The complex has a strong ability to quench the intrinsic fluorescence of HSA through static quenching procedure. The electrostatic force and hydrophobic interactions are dominant in the binding process based on the results of thermodynamic parameters (ΔH0 < 0 and ΔS0 > 0). The results of competitive binding measurements exhibited that the Sn(IV) complex bound to site II of HSA. Synchronous fluorescence, AFM, circular dichroism spectroscopy and molecular docking simulation results indicated that the binding of Sn(IV) complex to HSA induces the conformational changes of HSA. The in silico ADMET studies reveal that [SnMe2Cl2(bu2bpy)] and its ligand possess great biological potential. The results from cyclic voltammetry experiments also confirm interaction between HSA and Sn(IV) complex. Based on the non-radiative energy transfer theory of Forster, the binding distance between the complex (acceptor) and HSA (donor) was obtained (r = 1.77 nm). Furthermore, there was a good agreement between theoretical (molecular docking method) and experimental results. Finally, elucidation of the mechanism of anticancer activity revealed that Sn(IV) complex possesses potential cytotoxicity against MCF-7 breast cancer cells and is able to induce significant levels of apoptosis at concentrations below IC50 value.