Activation and inhibition of leukotriene A4 hydrolase aminopeptidase activity by diphenyl ether and derivatives

The synthesis and biological evaluation of a series of diphenyl ether derivatives were described. The compounds can either activate or inhibit the aminopeptidase activity of leukotriene A(4) hydrolase, while at the same time do not influence the hydrolase activity. Further enzyme kinetics and molecular modeling investigation on these novel chemical activators revealed their possible activation mechanism. These compounds can be used as probes to regulate the aminopeptidase activity of leukotriene A4 hydrolase. (C) 2008 Elsevier Ltd. All rights reserved.