Discovery of novel 1,2,4-triazole tethered β-hydroxy sulfides as bacterial tyrosinase inhibitors: synthesis and biophysical evaluation through in vitro and in silico approaches.

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.
Competing Interests: Authors have no conflict of interest for this research work.
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