Synthesis and bioactivities of 1-(4-hydroxyphenyl)-2-((heteroaryl)thio)ethanones as carbonic anhydrase I, II and acetylcholinesterase inhibitors

Authors : Cem YAMALİ, Halise Inci GUL, Yeliz DEMİR, Cavit KAZAZ, Ilhami GULCİN

Pages : 1058-1067

View : 23 | Download : 11

Publication Date : 0000-00-00

Article Type : Research Paper

Abstract :The discovery of enzyme targeting inhibitors is a popular area of drug research. Biological activities of the compounds bearing phenol and heteroaryl groups make them popular groups in drug design targeting important enzymes such as acetylcholinesterase insert ignore into journalissuearticles values(AChE, E.C.3.1.1.7); and carbonic anhydrases insert ignore into journalissuearticles values(CAs, EC 4.2.1.1);. 1-insert ignore into journalissuearticles values(4-hydroxyphenyl);-2-insert ignore into journalissuearticles values(insert ignore into journalissuearticles values(aryl);thio);ethanones as possible AChE and CAs inhibitors were synthesized, and their chemical structures were confirmed by IR, H-1 NMR, C-13 NMR, and HRMS. The compounds 2 and 4 were found potent AChE inhibitors with the Ki values of 22.13 +/- 1.96 nM and 23.71 +/- 2.95 nM, respectively, while the compounds 2 insert ignore into journalissuearticles values(Ki = 8.61 +/- 0.90 nM, on hCA I); and 1 insert ignore into journalissuearticles values(Ki = 8.76 +/- 0.84 nM, on hCA II); had considerable CAs inhibitory potency. The lead compounds may help the scientists for the rational designing of an innovative class of drug candidates targeting enzyme-based diseases.
Keywords : Carbonic anhydrases, acetylcholinesterase, heterocyclic, phenol