ScholarWorks@동국대학교

초록

5-Lipoxygenase (5-LO) is one of the significant drug targets for the development of various anti-inflammatory drugs. Herein, we designed, optimized, and synthesized a novel N-((6-(substituted-amino)-2-methyl-2H-chromen-2-yl)methyl)-N-methylbenzenesulfonamide derivatives as potential 5-LO inhibitors. Among the synthesized compounds, 10a, 10b, and 10g exhibited inhibitory activity toward 5-LO according to the in vitro studies including enzyme activity assay (>= 78% inhibition rate at 1 mu M) and cell-based assay (>= 72% inhibition rate at 1 mu M). 10b was selected for further in vivo efficiency using an ear edema mouse model, which was induced by arachidonic acid. Oral administration of 10b successfully suppressed ear edema and myeloperoxidase activity (MPO activity). Molecular docking studies showed alkyl and pi-alkyl interactions of compound 10b with Ile126 and Val110 of 5-LO as well as a hydrogen bonding with Arg138 as key protein-ligand interactions.

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