Organotellurium (IV) Complexes as Potent Antimalarial and Antimicrobial Agents: Synthesis, Biological Evaluation, and Computational Insights

Malaria is a major global health challenge. Plasmodium falciparum has developed resistance to several conventional drugs, necessitating the search for new therapeutic agents. In this study, we synthesized six novel Organotellurium (IV) complexes derived from 3-methyl-2-thiophene carboxaldehyde and p-aminophenol Schiff base. Spectroscopic analyses, including FT-IR, NMR, UV–Vis, FESEM, EDX, PXRD, and TGA, confirmed their structural integrity and stability. The biological evaluation demonstrated strong antimalarial activity, with complexes 6b (IC₅₀ = 0.48 μg/mL) and 6c (IC₅₀ = 0.42 μg/mL) showing the highest inhibition, comparable to quinine (IC₅₀ = 0.26 μg/mL). The antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans exhibited minimum inhibitory concentrations (MIC) ranging from 12.5 to 250 μg/mL, with 6b and 6c demonstrating superior efficacy. The antioxidant potential was significant, with 6d (IC₅₀ = 67.70 ± 0.42 μg/mL) showing higher radical scavenging activity than ascorbic acid (IC₅₀ = 70.70 ± 0.35 μg/mL). Molecular docking revealed strong binding affinities, with 6b binding to P. falciparum (binding energy: −7.8 kcal/mol) and C. albicans (−9.2 kcal/mol). DFT calculations confirmed low HOMO-LUMO energy gaps (6b: 3.46 eV, 6f: 3.42 eV), indicating high reactivity. Molecular dynamics simulations reinforced the stability of 6b and 6f, with RMSD values of 1.5–1.7 Å. ADMET profiling highlighted their high GI absorption, non-hepatotoxicity, and excellent bioavailability (6b: 0.85, 6f: 0.82), confirming their potential as drug candidates. These findings underscore the promise of Organotellurium (IV) complexes as novel antimalarial and antimicrobial agents for further preclinical evaluation.