Novel thioether and thioester-based derivatives as promising antibacterial agents with antioxidant potential: design, synthesis, and in silico studies.

AIM: Development of novel thioethers (5a-g), thioesters (6a-g), and bis-thioethers (8a-h) with antibacterial potential. MATERIALS AND METHODS: Twenty-one novel compounds were synthesized and evaluated for antimicrobial activity against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. Compounds with significant antibacterial activity were estimated for antioxidant potential and in silico studies. RESULTS AND DISCUSSION: Eight of the tested compounds demonstrated significant antibacterial activity, particularly versus B. cereus and S. aureus. The minimum inhibitory concentration (MIC) revealed the remarkable antibacterial activity and bactericidal behavior, as demonstrated by minimum bactericidal concentration (MBC) determination and time-kill kinetics studies of 8g and 8h, against S. aureus. Moreover, both compounds exhibited notable antibiofilm activity against S.aureus. Selectivity of the tested compounds as antibacterial agents was confirmed by low cytotoxicity toward normal cells. Remarkably, compounds 8b and 8g exhibited antioxidant potential (ABTS and DPPH) assays in comparison to ascorbic acid. Evaluation of antioxidant markers revealed that 8g displayed an increase in superoxide dismutase (SOD) and malondialdehyde (MDA) level. In silico studies revealed that the compounds exhibited acceptable ADME properties, with strong binding to the bacterial dihydrofolate reductase active site, along with dynamic stability of the DHFR-8g complex.