We have created a novel series of mushroom tyrosinase inhibitors with 1,2,4-triazole as fundamental skeleton. The target compound 1,2,4-triazol-3-ylthio)-N-phenyl acetamide derivatives 9(a-l) were synthesized by the reaction of 4- and 5-substituted 1,2,4-triazole-3-thiol derivatives 6(a-c) with 2-chloro-N-sub/un-substituted phenyl acetamide derivatives 8(a-d) under basic condition. By using the analytical techniques for instance, FTIR, LC-MS, 1H NMR and 13C NMR, the structural verification was evaluated. The novel series of the target compounds 9(a-l) has been scanned for biological activity (mushroom tyrosinase inhibition potential) which demonstrates adequate results. Interestingly, compound 9k (IC50 = 0.0048 ± 0.0016 µM) exhibits 3500 times more activity compared with standard drug kojic acid (IC50 = 16.8320 ± 1.1600 µM) against mushroom tyrosinase inhibitor. Furthermore, the cytotoxicity experiment was carried out for the highly effective target compounds (9d, 9i, 9j and 9k) by using MTT assay method for A375 human melanoma cells to define the nontoxic performance of the most effective compounds ranging from 1 to 25 µM. Furthermore, the molecular docking study delivers the thought concerning the interface of the ligand with an enzyme. Also, the dynamic simulation was accomplished for compound 9k to govern the plausible binding model.

中文翻译：

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作为蘑菇酪氨酸酶抑制剂的新型 1,2,4-三唑类似物：合成、动力学机制、细胞毒性和计算研究。


我们创建了一系列以1,2,4-三唑为基本骨架的新型蘑菇酪氨酸酶抑制剂。通过4-和5-取代的1,2,4-三唑-3-硫醇衍生物6反应合成目标化合物1,2,4-三唑-3-硫醇)-N-苯基乙酰胺衍生物9(al) (ac)与2-氯-N-sub/未取代的苯基乙酰胺衍生物8(ad)在碱性条件下反应。通过使用FTIR、LC-MS、1H NMR和13C NMR等分析技术，对结构进行了验证。已对目标化合物 9(a1) 的新系列的生物活性（蘑菇酪氨酸酶抑制潜力）进行了扫描，结果显示出足够的结果。有趣的是，与标准药物曲酸 (IC50 = 16.8320 ± 1.1600 µM) 相比，化合物 9k (IC50 = 0.0048 ± 0.0016 µM) 对蘑菇酪氨酸酶抑制剂的活性高出 3500 倍。此外，利用MTT测定方法对A375人黑色素瘤细胞进行高效目标化合物（9d、9i、9j和9k）的细胞毒性实验，以确定最有效化合物在1至25μM范围内的无毒性能。此外，分子对接研究提出了有关配体与酶界面的想法。此外，还对化合物 9k 进行了动态模拟，以控制合理的结合模型。