Synthesis and MAO inhibitory activity of novel thiazole-hydrazones

Authors : Özlem ATLI, Yusuf ÖZKAY

Pages : 685-699

View : 18 | Download : 6

Publication Date : 0000-00-00

Article Type : Research Paper

Abstract :A series of new thiazole-hydrazones 3a-3n were synthesized, characterized, and screened for their $h$MAO-A and $h$MAO-B inhibitory activity by an in vitro fluorometric method. Selectivity indexes insert ignore into journalissuearticles values(SIs); were expressed as IC$_{50}$ insert ignore into journalissuearticles values(MAO-A); / IC$_{50}$ insert ignore into journalissuearticles values(MAO-B);. Compound 3f showed promising $h$MAO-A inhibition with an IC$_{50}$ value of 1.20 $\mu $M and displayed a very significant SI of 0.04 towards $h$MAO-A. The mechanism of $h$MAO-A inhibition was investigated by enzyme kinetics using Lineweaver--Burk graphics. Compound 3f was further screened for its cytotoxicity by using a healthy NIH/3T3 mouse embryonic fibroblast cell line insert ignore into journalissuearticles values(ATCC CRL1658); and was evaluated as nontoxic at its effective concentration against $h$MAO-A. The ADME prediction of the compounds revealed that they may have good pharmacokinetic profiles, which is necessary for drug candidates.
Keywords : Thiazole, hydrazone, h MAO enzymes, enzyme inhibition