Structural dynamics and evaluation of anti-proliferative effects of di-n-butyltin and triphenyltin fluoroazosalicylates on DU-145 prostate cancer cells

Four organotin(IV) derivatives of composition [Me₂Sn(HL)₂] 1, [n-Bu₂Sn(HL)₂] 2, [n-Oct₂Sn(HL)₂] 3 and [Ph₃Sn(HL)] 4 were synthesized by reacting 5-[(E)-2-(4-fluorophenyl)-1-diazenyl]-2-hydroxybenzoic acid (H'HL) with Me₂SnO, n-Bu₂SnO, n-Oct₂SnO and Ph₃SnOH respectively. Compounds 1–4 were fully characterized by elemental analysis, IR and NMR (¹H, ¹³C, ¹⁹F and ¹¹⁹Sn) spectroscopy, and additionally, the molecular and crystal structures of 1, 2 and 4 were established by single-crystal X-ray diffraction analysis. X-ray data indicated that the compounds 1 and 2 adopt the same structural motif and reveal a monomeric molecule. The carboxylate group on the ligand acts as bidentate chelating agents, giving an equatorial plane around the tin atom of four asymmetrically coordinated oxygen atoms while Me₂ or n-Bu₂ groups are in axial positions giving rise to a skew-trapezoidal bipyramidal arrangement. On the other hand, triphenyltin complex 4 adopts a monomeric distorted tetrahedral configuration with the carboxylate ligand coordinating in a monodentate mode. In vitro anti-proliferative effects of [n-Bu₂Sn(HL)₂] 2 and [Ph₃Sn(HL)] 4 were tested against prostate cancer (DU-145) and normal human embryonic kidney (HEK-293) cells. The investigation into its mechanism of action includes conducting AO/EB (acridine orange/ethidium bromide) assays and assessing ROS (reactive oxygen species) generation, which indicated apoptosis through nuclear changes and ROS-induced cell death. Comparing the IC₅₀ values with those of analogous systems reveals that the results are significantly affected in both 2 and 4, and could be attributed to the presence of the fluorine atom in the ligand molecule. Among 2 and 4, triphenyltin compound 4 showed the strongest activity, with an IC₅₀ of 1.99 ± 0.18 μM.