A library of indolinedione–coumarin hybrid molecules was rationally designed and synthesized against hyperuricemia. All of the synthesized hybrid molecules were tested to check their inhibitory activity against xanthine oxidase enzyme by using a spectrophotometric assay. The results revealed that the compound showed IC₅₀ values within the range of 6.5–24.5 µM amongst which compound K-7 was found to be endowed with the most potent IC₅₀ value against xanthine oxidase enzyme. Kinetic studies were also performed to check the mode of inhibition of most potent compound K-7, which revealed its mixed-type inhibition behavior. Structure-activity relationships revealed that electron-donating groups and small alkyl chains between the two active scaffolds might be beneficial in inhibiting xanthine oxidase enzyme. It was also shown that various electrostatic interactions stabilized the compound K-7 within the active site of xanthine oxidase enzyme, which confirmed that it can completely block its catalytic active site. Thus, K-7 is regarded as a potent xanthine oxidase inhibitor and can be served as a promising molecular architectural unit for anti-hyperuricemic drug design.

中文翻译：

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黄嘌呤氧化酶抑制剂新型吲哚啉二酮-香豆素杂种的设计，合成及生物学评价

合理设计并合成了吲哚啉二酮-香豆素杂合分子文库，以对抗高尿酸血症。通过使用分光光度法测试所有合成的杂合分子，以检查它们对黄嘌呤氧化酶的抑制活性。结果表明，该化合物的IC ₅₀值在6.5-24.5 µM范围内，其中化合物K-7被发现具有最强的抗黄嘌呤氧化酶的IC ₅₀值。还进行了动力学研究，以检查最有效的化合物K-7的抑制方式，揭示了其混合型抑制行为。构效关系揭示了两个活性支架之间的供电子基团和小的烷基链可能对抑制黄嘌呤氧化酶有帮助。还显示出各种静电相互作用将化合物K-7稳定在黄嘌呤氧化酶的活性位点内，这证实了它可以完全阻断其催化活性位点。因此，K-7被认为是有效的黄嘌呤氧化酶抑制剂，可以用作抗高尿酸药物设计的有希望的分子结构单元。