N-1, C-3 substituted indoles as 5-LOX inhibitors-In vitro enzyme immunoaasay, mass spectral and molecular docking investigations

Based upon the structures of some known 5-LOX inhibitors, a set of five compounds carrying appropriate substituents at N-1 and C-3 of indole were synthesized and investigated for 5-LOX inhibitory activities. Fifty percent inhibitory concn (IC50) of these compounds ranges from 0.6 to 5 mu M and found to be comparable to that of clinically used 5-LOX inhibitor, zileuton. The compounds under present investigations exhibited appreciable interactions with 5-LOX as apparent from their association constants calculated from the mass spectral data. Compound 5a with a tosyl group at N-1 and pyrolidinyl-1,2-dione substituent at C-3 of indole, exhibiting IC50 0.6 mu M and stoichiometry of 1:7 in the enzyme-compound complex was identified as highly potent 5-LOX inhibitor and seems to be suitable for further investigations. (C) 2012 Elsevier Ltd. All rights reserved.