Design, synthesis and in vitro COX inhibitory profiles of a new series of tetrazole-based hydrazones

Abstract

Inhibition of cyclooxygenases (COXs), by selective and nonselective inhibitors, is a favorable approach for pharmacologic intervention in a variety of disorders such as cancer. For this purpose, a new class of tetrazole-hydrazone hybrids (1-12) was designed. A facile and efficient procedure was applied for the preparation of compounds 1-12, which were tested for their inhibitory activities towards cyclooxygenases (COXs) by means of an in vitro colorimetric method. The most potent and selective COX-1 inhibitors were determined as 2-[(1-methyl-1H-tetrazol-5-yl)thio]-N'-(4-(piperidin-1-yl)benzylidene)acetohydrazide (1) (40.88±2.79%) and 2-[(1-methyl-1H-tetrazol-5-yl)thio]-N'-(4-(morpholin-4-yl)benzylidene)acetohydrazide (2) (39.80±2.78%), whereas the most potent and selective COX-2 inhibitor was found as 2-[(1-phenyl-1H-tetrazol-5-yl)thio]-N'-(4-(pyrrolidin-1-yl)benzylidene)acetohydrazide (10) (42.38±1.16%). In general, 1-methyl-1H-tetrazole moiety resulted in selective COX-1 inhibition, whereas 1-phenyl-1H-tetrazole moiety gave rise to preferential COX-2 inhibition.