Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
Bioorg Chem. 2018 Sep;79:293-300. doi: 10.1016/j.bioorg.2018.04.026. Epub 2018 Apr 30.
Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound 3f (IC = 1.568 ± 0.01 µM) showed relatively better potential compared to reference kojic acid (IC = 16.051 ± 1.27 µM). A comparative docking studies showed that compound 3f have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-6.90 kcal/mol) as compared to Kojic acid. The 4-methoxy group in compound 3f shows 100% interaction with Cu. Compound 3f displayed hydrogen binding interaction with His61 and His94 at distance of 1.71 and 1.74 Å which might be responsible for higher activity compared to Kojic acid.
芳基吡唑是一类在几种市售药物中发现的杂环化合物，受到广泛认可。鉴于其在药物化学中的重要性，在本报告中，我们通过Suzuki 交叉偶联反应合成了一系列适当取代的芳基吡唑。所有化合物均在体外和计算水平上评估了对蘑菇酪氨酸酶的抑制作用。化合物 3f（IC = 1.568 ± 0.01 µM）与参考曲酸（IC = 16.051 ± 1.27 µM）相比，显示出相对更好的潜力。比较对接研究表明，化合物 3f 与蘑菇酪氨酸酶（PDBID：2Y9X）具有最大的结合亲和力，结合能值为-6.90 kcal/mol，而曲酸为-5.23 kcal/mol。与化合物 3f 中的 4-甲氧基与 Cu 表现出 100%的相互作用。化合物 3f 与 His61 和 His94 显示出氢键相互作用，距离分别为 1.71 和 1.74 Å，这可能是与曲酸相比活性更高的原因。
