Green Synthesis and In Silico Evaluation of a Novel Thiazolidinone Thiourea Scaffold Targeting Orientia tsutsugamushi

Abstract

A novel series of 1-(2-(4-chlorophenyl)-4-oxothiazolidin-3-yl)thiourea derivatives was successfully synthesized via a tetrabutylammonium bromide–catalyzed multicomponent condensation involving substituted aldehydes, amines, and thioglycolic acid. The molecular structures of the synthesized 4CTA derivatives were unequivocally confirmed through comprehensive spectroscopic analyses, including FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometry. In silico studies were conducted against Orientia tsutsugamushi, Candida albicans, and Staphylococcus aureus the etiological agents of scrub typhus, fungal, and bacterial infections, respectively to evaluate the prospective biological efficacy and to correlate computational predictions with experimental findings. The developed synthetic methodology is environmentally benign and operationally efficient, delivering excellent yields (>95%), markedly reduced reaction times, and a broad substrate scope, thereby highlighting its applicability for the rapid construction of biologically relevant thiazolidinone scaffolds. To further elucidate the pharmacological significance, ADMET and ProTox computational assessments were performed, revealing favorable pharmacokinetic profiles and low predicted toxicity. Additionally, Density Functional Theory (DFT) calculations were employed to explore the electronic properties and reactivity descriptors of the active compounds, providing deeper insight into their stability and potential mechanisms of action.