Synthesis, characterization and bioactivity of diorganotin(iv) Schiff base complexes as potential antimalarial and antioxidant agents: insights through cytotoxicity and molecular docking studies

Abstract

The incidence of infectious ailments is increasing rapidly globally, causing a high rate of mortality and morbidity. In pursuit of new and effective anti-infectious agents, this research presents the synthesis of eight diorganotin(IV) complexes (3–10), derived from 1-naphthyl thiourea and ketone derivatives. Comprehensive structural analysis, employing FT-IR, NMR (¹H, ¹³C, and ¹¹⁹Sn), SEM-EDAX, TGA, P-XRD and mass spectrometry, demonstrated that the ligands chelated with diorganotin(IV) ions through O-, S- and N-donor sites adopted a penta-coordinated geometry. Biological assays showed that the complexes had enhanced bio-efficacy relative to their corresponding ligands, with activity ranked in the order of Ph₂SnL^1–2 > Bu₂SnL^1–2 > Et₂SnL^1–2 > Me₂SnL^1–2. Notably, complexes 6 (Ph₂SnL¹) and 10 (Ph₂SnL²) exhibited the highest malaria and oxidant controlling properties, with IC₅₀ values ranging from 0.83 ± 0.08 to 0.95 ± 0.15 μM and 2.82 ± 0.03 to 3.09 ± 0.01 μM, respectively, comparable to their standard agents. The cytotoxicity evaluation against Vero cells also showed that complex 6 (Ph₂SnL¹) had the lowest toxicity (21.96% ± 0.09%) at a concentration of 3.12 μg mL⁻¹. Moreover, the molecular docking study revealed its lowest binding score of −9.7 kcal mol⁻¹ and significant hydrophobic interactions with key residues against 1U5A protein, demonstrating its higher bio-efficacy compared to ligand 1 (H₂L¹). Also, theoretical and computational studies, along with ADMET Lab 2.0 evaluation, highlighted the bioactivity of complex 6 (Ph₂SnL¹), suggesting its potential application in the medicinal sector due to its compliance with Lipinski's Rule of Five and strong pharmacokinetic properties, including oral bioavailability, permeability, and clearance, comparable to standard drugs.