Exploring Antiplasmodial, Antimicrobial, Antioxidant, and Docking Profile: Conjugating Organotin Moiety With Hydrazones for Enhanced Efficacy

ABSTRACT

In the 21st century, pathogenic deformities contribute significantly to global morbidity and mortality. Our research investigates the antimalarial, antimicrobial, and antioxidant activities of newly synthesized hydrazones and their organotin (IV) complexes, derived from 2‐benzoyl‐1H‐indene‐1,3(2H)‐dione and 2‐phenoxypropanehydrazide/2‐(2,4‐dichlorophenoxy)propanehydrazide. Structural confirmation was achieved through multinuclear nuclear magnetic resonance (NMR), UV–Vis, IR, HRMS, thermogravimetric analysis (TGA), and scanning electron microscopy (SEM)‐energy‐dispersive X‐ray analysis (EDAX), revealing tridentate coordination of ligands to the tin metal via imine nitrogen and two enolic oxygens, forming a pentacoordinated geometry. The SEM analysis revealed that hydrazone ligand (1) exhibits a rectangular bar‐like microstructure, whereas its complex (5) shows a rugged surface with distinct territorial patches. Compounds (5) [Bu₂SnL¹] and (6) [Ph₂SnL¹] stood out with significant bioactivity, with antimalarial IC₅₀ values ranging from 0.54 ± 0.07 to 0.67 ± 0.06 μM and antioxidant IC₅₀ values from 4.39 ± 0.02 to 4.67 ± 0.01 μM. Additionally, compounds (6) [Ph₂SnL¹] and (10) [Ph₂SnL⁴] exhibited the highest antimicrobial activity, with MIC values ranging from 0.0045 to 0.0042 μmol/mL, respectively, comparable to standard drugs. Complementing the experimental data, in silico molecular docking studies were performed on the most effective ligand (1) [H₂L¹] and its phenyl complex (6) [Ph₂SnL¹] with Plasmodium falciparum lactate dehydrogenase, revealing binding energies of −6.0 and −6.9 kcal/mol, respectively, and corroborating the experimental findings. Further, comprehensive absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluations were performed on each compound to gauge their suitability as drug candidates and potential for toxicity.