Abstract
In this study, a series of 1,2,4-triazole-tethered β-hydroxy sulfide scaffolds 11a-h was synthesized in good to remarkable yields (69-90%) through the thiolysis of oxiranes by the thiols in aqueous basic catalytic conditions. The synthesized 1,2,4-triazole-tethered β-hydroxy sulfides were screened against bacterial tyrosinase enzyme, and Gram-positive and Gram-negative bacterial cultures i.e., (S. aureus) Staphylococcus aureus & (E. coli) Escherichia coli. Among the synthesized derivatives, the molecules 11a (IC(50) = 7.67 ± 1.00 μM), 11c (IC(50) = 4.52 ± 0.09 μM), 11d (IC(50) = 6.60 ± 1.25 μM), and 11f (IC(50) = 5.93 ± 0.50 μM) displayed the better tyrosinase inhibitory activity in comparison to reference drugs ascorbic acid (IC(50) = 11.5 ± 1.00 μM) and kojic acid (IC(50) = 30.34 ± 0.75 μM). The molecule benzofuran-triazol-propan-2-ol 11c proved to be the most potent bacterial tyrosinase inhibitory agent with a minimum IC(50) of 4.52 ± 0.09 μM, as compared to other synthesized counterparts and both standards (kojic acid and ascorbic acid). The compound diphenyl-triazol-propan-2-ol 11a and benzofuran-triazole-propan-2-ol 11c showed comparable anti-bacterial chemotherapeutic efficacy with minimum inhibitory concentrations (MIC = 2.0 ± 2.25 mg mL(-1) and 2.5 ± 0.00 mg mL(-1), respectively) against S. aureus bacterial strain in comparison with standard antibiotic penicillin (MIC = 2.2 ± 1.15 mg mL(-1)). Furthermore, among the synthesized derivatives, only compound 11c demonstrated better anti-bacterial activity (MIC = 10 ± 0.40 mg mL(-1)) against E. coli, which was slightly less than the standard antibiotic i.e., penicillin (MIC = 2.4 ± 1.00 mg mL(-1)). The compound 11c demonstrated a better binding score (-7.08 kcal mol(-1)) than ascorbic acid (-5.59 kcal mol(-1)) and kojic acid (-5.78 kcal mol(-1)). Molecular docking studies also validate the in vitro anti-tyrosinase assay results; therefore, the molecule 11c can be the lead bacterial tyrosinase inhibitor as well as the antibacterial agent against both types of bacterial strains after suitable structural modifications.