Optimization of 1,3-thiazolidin-4-one based compounds: Design, synthesis, biological evaluation, molecular modeling and ADME studies

A series of thiazolidinone derivatives (5a-f) was constructed and the structure of these compounds was elucidated by IR, ¹H NMR, ¹³C NMR, and elemental analyses. The prepared compounds were assessed for their antimicrobial and antioxidant potential. The obtained results from antimicrobial screening revealed that 2-hydroxy-4-(2-(4-nitrophenyl)-4-oxothiazolidin-3-yl)benzoic acid (5b) and 2-hydroxy-4-(2-(4-hydroxyphenyl)-4-oxothiazolidin-3-yl) benzoic acid (5c) were the most active against all tested bacterial species (ZI = 29–42 mm; MIC = 75–128 μg/mL) and were more active than ampicillin (ZI = 26–30 mm; MIC = 100–150 μg/mL). Regarding antioxidant activity, thiazolidinone derivatives 5c (IC₅₀ = 20.43 μg/mL), 5e (IC₅₀ = 21.06 μg/mL), and 5f (IC₅₀ = 22.18 μg/mL) were the most active compounds in comparison to the reference drug ascorbic acid (IC₅₀ = 17.13 μg/mL). A docking study of the thiazolidinone derivatives 5a-f inside the DNA gyrase active site was conducted in an attempt to predict the binding modes of these compounds. All the docked candidates 5a-f recorded high binding score forming hydrogen bonding interactions and other hydrophobic bindings with the essential amino acid LYS103. In addition, ADME study was conducted to predict suitability of the constructed compounds to be oral drug candidates. The results of this work suggested that thiazolidinone derivatives could be promising antimicrobial agents with considerable antioxidant potential.