Thiazolidinone Derivatives as Next-Generation Antifungal Scaffolds: Synthesis and QSAR Study

A novel series of 1,3-thiazolidin-4-one-5-arylidene derivatives was synthesized and evaluated for antifungal activity against Aspergillus flavus. The chemical structures were characterized by ¹H/¹³C NMR spectroscopy, along with HRMS. In vitro assays revealed moderate to strong activity, with MICs ranging from 15.565 to 238.942 µM, compared with itraconazole as a reference. Structure–activity analysis indicated that para-substituted electron-donating groups enhanced biological affinity. Compound 7b (4-dimethylamine) exhibited the highest potency. A QSAR study on derivatives 7a-j identified dipole moment (μD), lipophilicity (LogP), and polarizability (Pol) as key descriptors, with lipophilicity emerging as the most influential. Lower polarity favored stronger antifungal activity, and all derivatives except 7a contributed significantly to the predictive model. These findings highlight the promise of thiazolidinone scaffolds as viable leads for next-generation antifungal agents.