Synthesis, Docking Study, and Structural Characterization of New Bioactive Thiazolidine-4-one Derivatives as Antibacterial and Antioxidant Agents

Abstract

Objective: This study involved the design and synthesis of new thiazolidine-4-one derivatives, as well as testing their antioxidant activity and evaluating their potential as antibacterial agents. Methods: Thiazolidine-4-one compounds (T-1) and (T-2) were synthesized by reacting 2-mercaptoacetic acid with the synthesized imines, (Im-1) and (Im-2), respectively. The synthesized compounds were characterized by physicochemical and spectrophotometric data (UV-Vis, FT-IR, ¹H, ¹³C NMR, and CHN analysis). Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli) were used as test organisms for the antibacterial activity of (T-1) and (T-2). Molecular docking experiments were performed to gain an understanding of the affinity and interaction between thiazolidine-4-one molecules and glucosamine-6-phosphate synthase (GA6PS). Hemolysis assays and DPPH^·/ABTS^·+ scavenging activity of (T-1) and (T-2) were studied. Results and Discussion: The results showed strong antibacterial activity of (T-2) compared to ciprofloxacin as a standard in inhibiting the growth of P. aeruginosa and E. coli, while its antibacterial effect in inhibiting the growth of S. aureus was stronger than ciprofloxacin. The data obtained from the docking studies were in perfect agreement with the data from the in vitro antibacterial test. Compound (T-2) showed good binding affinity to GA6PS, which is an important enzyme for bacterial cell wall synthesis, making (T-2) a promising antibacterial agent. The thiazolidine-4-ones (T-1) and (T-2) showed strong antioxidant activity, and non-toxicity was confirmed by the hemolysis method. Conclusions: We propose that one of the mechanisms behind the antibacterial activity of the synthesized thiazolidin-4-ones is the disruption of bacterial cytoplasmic membrane integrity, and therefore, these compounds have favorable properties for potential biomedical applications and positive future prospects.