Glutamine conjugated organotin(IV) Schiff base compounds: Synthesis, structure, and anticancer properties

Abstract

AbstractHerein, glutamine conjugated organotin(IV) Schiff base compounds, [(SBGlu‐Naph)Sn (Me)2] (1), [(SBGlu‐Naph)Sn(n‐Bu)2] (2), [(SBGlu‐Sali)Sn (Me)2] (3), [(SBGlu‐Sali)Sn(n‐Bu)2] (4) and [(SBGlu‐Sali)Sn (Ph)2] (5), were synthesized by one‐pot reaction with an aldehyde (2‐hydroxy‐1‐naphthaldehyde) for 1 and 2, and 5‐methyl‐2‐hydroxybenzaldehyde (for 3–5) and respective diorganotin oxide. The compounds were characterized using elemental micro‐analyses, spectroscopic techniques (FT‐IR, 1H NMR, 13C NMR, and 119Sn NMR), mass spectrometry, and single‐crystal X‐ray diffraction analyses. Based on in‐silico ADME (absorption, distribution, metabolism, and excretion) and drug‐likeness properties, compounds 1, 3, and 4 were selected to investigate their DNA/Protein binding properties with calf thymus DNA (CT‐DNA) and bovine serum albumin (BSA) using spectrophotometry and spectrofluorimetry. The intercalative mode of binding with CT‐DNA was supported by molecular docking simulations. The emission spectral data of compounds with CT‐DNA showed 1 as a groove binder, and 3 and 4 as an intercalator which was confirmed by competitive displacement assays. Similarly, static and dynamic mode of interaction between the compounds and BSA was found. Furthermore, these compounds were screened for their cytotoxic activity against two human cancer cell lines; PC‐3 (Prostate) and Mg‐63 (Osteosarcoma) at different concentrations. Quantitative structure–activity relationship (QSAR)‐based regression models were developed and implemented on compounds 1, 3, and 4 that inferred compound 3 to be the most potential candidate for further in vivo studies.