Design, synthesis and biological evaluation of novel indolinedione-coumarin hybrids as xanthine oxidase inhibitors

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 IC(50)values within the range of 6.5-24.5 mu M amongst which compoundK-7was found to be endowed with the most potent IC(50)value against xanthine oxidase enzyme. Kinetic studies were also performed to check the mode of inhibition of most potent compoundK-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 compoundK-7within the active site of xanthine oxidase enzyme, which confirmed that it can completely block its catalytic active site. Thus,K-7is regarded as a potent xanthine oxidase inhibitor and can be served as a promising molecular architectural unit for anti-hyperuricemic drug design.