Organotin(IV) complexes derived from 2,6-diacetylpyridine bis(2-hydroxybenzoylhydrazone) as prospective anti-proliferative agents: Synthesis, characterization, structures and in vitro anticancer activity

Abstract

Six organotin(IV) complexes, viz., [Me₂Sn(L)] (1), [n-Bu₂Sn(L)] (2), [n-Oct₂Sn(L)] (3), [Bz₂Sn(L)]·0.5C₇H₈ (4), [n-BuSn(L)Cl] (5), and [PhSn(L)Cl] (6), were synthesized using a 2,6-diacetylpyridine bis(2-hydroxybenzoylhydrazone), H₂L. Compounds were characterized by Fourier transform infrared (FT-IR), High-resolution mass spectrometry (HRMS), and solutions Fourier transform nuclear magnetic resonance (FT-NMR) spectroscopies. The structures 1–6 were established by single-crystal X-ray diffraction (SC-XRD) analysis. Diffraction results evidenced that complexes 1–6 were seven-coordinated mononuclear species with the equatorial plane comprising the pentagonal N₃O₂ chelate ring of the doubly deprotonated L and two axial ligands, either R (R = Me, n-Bu, n-Oct, Bz) or R (n-Bu or Ph) and Cl ligands. Additionally, the photophysical properties were examined due to the enhanced conjugation and rigidity of the molecules while thermogravimetric analysis was carried out to evaluate the thermal stabilities of compounds. The anti-proliferative activity of the complexes 1–6 was tested against prostate cancer cells (DU-145) and normal human embryonic kidney cells (HEK-293). Among the compounds, dibutyltin compound 2 exhibited increased anti-proliferative activity, with an IC₅₀ value of 6.16 ± 1.56 μM. The investigation of its mechanism of action involves using AO/EB (acridine orange/ethidium bromide) and ROS (reactive oxygen species) generation assays. This likely detects apoptotic morphological alterations in the nucleus of the cells, with ROS generation ultimately leading to apoptosis and cell death. The superior activity of 2 may be attributed to the C···H contacts and respective higher d_e outside and d_i inside distances from the Hirshfeld surface. Thus, these compounds could be a promising alternative to classical chemotherapy agents.