Design and Eco-Friendly Synthesis of 4-Oxothiazolidinone-Thiourea Derivative: In Silico Antimicrobial Evaluation and DFT Studies

Abstract

A novel 1-(2-(4-methylphenyl)-4-oxothiazolidin-3-yl)thiourea derivative is synthesized through a tetrabutylammonium bromide catalyzed multicomponent condensation involving 4-methyl substituted aldehydes, amines, and thioglycolic acid. The molecular structures of the obtained 4CTA derivatives are confirmed using FT-IR, ¹H NMR, and ¹³C NMR spectroscopic techniques. In silico studies target Orientia tsutsugamushi, the causative agent of scrub typhus, to evaluate the potential biological activity and to correlate computational results with experimental findings. The developed synthetic protocol demonstrates environmental sustainability and operational simplicity, affording excellent yields (>95%), reduced reaction times, and a broad substrate scope, which highlights its suitability for the rapid synthesis of biologically relevant thiazolidinone frameworks. ADMET and ProTox computational evaluations are carried out to assess pharmacological relevance, indicating favorable pharmacokinetic properties and low predicted toxicity. Density Functional Theory (DFT) calculations are employed to investigate the electronic properties and reactivity profiles of the active compounds, providing insight into their stability and possible mechanisms of action.