Synthesis, Characterization and Bioactivity of Diorganotin(IV) Schiff Base Complexes as Potential Antimalarial and Antioxidant Agents: Insight through Cytotoxicity and Molecular Docking

Abstract

The infectious ailments are raising on rapid scale 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, demonstrate that the ligands chelated with diorganotin(IV) ion through O-, S- and N- donor sites, adopting an pentacoordinated geometry. Biological assays states that the complexes have enhanced bio-efficacy relative to their corresponding ligands, with activity ranked as Ph₂SnL1-2 > Bu₂SnL1-2 > Et₂SnL1-2 > Me₂SnL1-2. Notably, complexes 6 (Ph2SnL1) and 10 (Ph2SnL2) exhibited highest malaria and oxidant controlling properties, with IC50 values ranging from 0.83 ± 0.08 - 0.95 ± 0.15 µM and 2.82 ± 0.03 - 3.09 ± 0.01 µM, correspondingly, comparable to their standard agents. The cytotoxicity evaluation against Vero cells also states that the complex 6 (Ph2SnL1) has lowest toxicity (21.96 ± 0.09 %) at 3.12 µg/mL concentration. Moreover, molecular docking study also reveals lowest binding score of -9.7 kcal/mol and significant hydrophobic interactions with key residues against 1U5A protein, demonstrating its highest bio-efficacy compared to ligand 1(H2L1). Theoretical and computational studies, along with ADMET Lab 2.0 evaluation, highlight 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.