Indole derivatives as potent inhibitors of 5-lipoxygenase: Design, synthesis, biological evaluation, and molecular modeling

A series of novel indole derivatives was designed, synthesized and evaluated by cell-based assays for their inhibitory activities against 5-LOX in rat peritoneal leukocytes. Most of them (30 out of 35) showed an inhibitory potency higher than the initial screening hit 1a (IC50 = 74 μM). Selected compounds for concentration–response studies showed prominent inhibitory activities with IC50 values ranging from 0.74 μM to 3.17 μM. Four compounds (1m, 1s, 4a, and 6a) exhibited the most potent inhibitory activity compared to that of the reference drug (Zileuton), with IC50 values less than 1 μM. Molecular modeling studies for compounds 1a, 3a, 4a, and 6a were also presented. The excellent in vitro activities of this class of compounds may possess potential for the treatment of LT-related diseases.

Four compounds (1m, 1s, 4a, and 6a) exhibited the potent inhibitory activity against 5-LOX in rat peritoneal leukocytes, with IC50 values ranging from 0.74 μM to 0.95 μM, which is very close to the reference drug (Zileuton, IC50 = 0.83 μM).Figure optionsDownload as PowerPoint slide