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Saeed, Sadaf, Saif, Muhammad Jawwad, Zahoor, Ameer Fawad, Tabassum, Hina, Kamal, Shagufta, Faisal, Shah, Ashraf, Rabia, Khan, Samreen Gul, Nazeer, Usman, Irfan, Ali and Bhat, Mashooq Ahmad (2024) 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. RSC Advances, 14 (22). pp. 15419-15430. ISSN 2046-2069
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 (IC50 = 7.67 ± 1.00 μM), 11c (IC50 = 4.52 ± 0.09 μM), 11d (IC50 = 6.60 ± 1.25 μM), and 11f (IC50 = 5.93 ± 0.50 μM) displayed the better tyrosinase inhibitory activity in comparison to reference drugs ascorbic acid (IC50 = 11.5 ± 1.00 μM) and kojic acid (IC50 = 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 IC50 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.
Available under License Creative Commons Attribution Non-commercial.
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