期刊
CHEMMEDCHEM
卷 -, 期 -, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.202300400
关键词
Hydroxy-3-phenylcoumarins; Hydroxy-3-thienylcoumarins; Xanthine oxidase; Molecular docking
The coumarin scaffold shows promise in the development of bioactive agents, and this study focuses on the synthesis and evaluation of hydroxylated 3-arylcoumarins for their XO inhibition and antioxidant properties. Compound 11 is found to be the most potent XO inhibitor, and both compounds 11 and 5 show mixed-type inhibition and good antioxidant activity. Molecular docking studies correlate the theoretical and experimental binding affinity to the XO binding pocket.
Coumarin scaffold has proven to be promising in the development of bioactive agents, such as xanthine oxidase (XO) inhibitors. Novel hydroxylated 3-arylcoumarins were designed, synthesized, and evaluated for their XO inhibition and antioxidant properties. 3-(3'-Bromophenyl)-5,7-dihydroxycoumarin (compound 11) proved to be the most potent XO inhibitor, with an IC50 of 91 nM, being 162 times better than allopurinol, one of the reference controls. Kinetic analysis of compound 11 and compound 5 [3-(4'-bromothien-2'-yl)-5,7-dihydroxycoumarin], the second-best compound within the series (IC50 of 280 nM), has been performed, and both compounds showed a mixed-type inhibition. Both compounds present good antioxidant activity (ability to scavenge ABTS radical) and are able to reduce reactive oxygen species (ROS) levels in H2O2-treated cells. In addition, they proved to be non-cytotoxic in a Caco-2 cells viability assay. Molecular docking studies have been carried out to correlate the compounds' theoretical and experimental binding affinity to the XO binding pocket.
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