Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Chemistry, Indo-Soviet Friendship College of Pharmacy, Moga-142 001, Punjab, India.
Bioorg Med Chem. 2011 Mar 15;19(6):1950-8. doi: 10.1016/j.bmc.2011.01.058. Epub 2011 Feb 23.
Xanthine oxidase is a complex molybdoflavoprotein that catalyses the hydroxylation of xanthine to uric acid. Fifty three analogues of 1-acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles were rationally designed and synthesized and evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Some notions about structure activity relationships are presented. Six compounds 41, 42, 44, 46, 55 and 59 were found to be most active against XO with IC(50) ranging from 5.3 μM to 15.2 μM. The compound 59 emerged as the most potent XO inhibitor (IC(50)=5.3 μM). Some of the important interactions of 59 with the amino acid residues of active site of XO have been figured out by molecular modeling.
黄嘌呤氧化酶是一种复杂的钼黄素蛋白，能够催化黄嘌呤羟化为尿酸。首次对 1-乙酰基-3,5-二芳基-4,5-二氢(1H)吡唑啉酮的 53 个类似物进行了合理设计和合成，并对其体外黄嘌呤氧化酶抑制活性进行了评估。提出了一些关于构效关系的观点。发现化合物 41、42、44、46、55 和 59 对 XO 的抑制活性最强，IC50 范围为 5.3 μM 至 15.2 μM。化合物 59 是最强的 XO 抑制剂（IC50=5.3 μM）。通过分子模拟，确定了化合物 59 与 XO 活性部位氨基酸残基的一些重要相互作用。
