2-Hydroxy-1-naphthaldehyde-based organotin(IV) complexes: structural aspects, cytotoxicity, DNA binding interaction, and molecular docking

A series of organotin(IV) complexes (2a–2d) derived from 2-hydroxy-1-naphthaldehyde and pyridoxamine were obtained in good yields via a one-pot strategy. 119 Sn NMR confirmed hexacoordinated species in solution, and single-crystal X-ray diffraction of 2d revealed a distorted trigonal–bipyramidal geometry (τ = 0.65) with a C 2 NO 2 donor set. UV–Vis and fluorescence titrations with CT-DNA demonstrated intercalative binding ( K b = 7.66–11.0 × 10 4 M −1 ), and isothermal titration calorimetry confirmed spontaneous, exothermic binding to ssDNA, with complex 2c showing stronger affinity than 2b due to combined enthalpic and entropic contributions. All complexes exhibited significantly higher cytotoxicity than cisplatin against MCF-7 and MDA-MB-231 breast cancer cell lines; 2c and 2d were the most potent (IC 50 = 0.06–0.26 μM), with 2d showing the best selectivity index (SI = 2.33 for MCF-7). Flow cytometry revealed cell-line-dependent mechanisms: MDA-MB-231 cells underwent cytostatic mitotic blockade, with suppression of S and G2/M phases, whereas MCF-7 cells exhibited features of apoptosis and G1 accumulation. Molecular docking against CDK2/cyclin A showed binding energies of −9.31 to −10.27 kcal/mol, substantially higher than cisplatin (− 4.09 kcal/mol), with 2d displaying the strongest affinity, consistent with its higher biological activity.