Synthesis and pharmacological effects of novel benzenesulfonamides carrying benzamide moiety as carbonic anhydrase and acetylcholinesterase inhibitors

Authors : Mehtap TUGRAK, Halise Inci GUL, Baris ANİL, Ilhami GULCİN

Pages : 1601-1609

View : 14 | Download : 5

Publication Date : 0000-00-00

Article Type : Research Paper

Abstract :N-insert ignore into journalissuearticles values(1-insert ignore into journalissuearticles values(4-Methoxyphenyl);-3-oxo-3insert ignore into journalissuearticles values(insert ignore into journalissuearticles values(4-insert ignore into journalissuearticles values(N-insert ignore into journalissuearticles values(substituted);sulfamoyl);phenypamino);prop-1-en-1-yl);benzamides 3a - g were designed since sulfonamide and benzamide pharmacophores draw great attention in novel drug design due to their wide range of bioactivities including acetylcholinesterase insert ignore into journalissuearticles values(AChE); and human carbonic anhydrase I and II insert ignore into journalissuearticles values(hCA I and hCA II); inhibitory potencies. Structure elucidation of the compounds was carried out by H-1 NMR, C-13 NMR, and HRMS spectra. In vitro enzyme assays showed that the compounds had significant inhibitory potential against hCA I, hCA II, and AChE enzymes at nanomolar levels. Ki values were in the range of 4.07 +/- 0.38 - 29.70 +/- 3.18 nM for hCA I and 10.68 +/- 0.98 - 37.16 +/- 7.55 nM for hCA II while Ki values for AChE were in the range of 8.91 +/- 1.65 - 34.02 +/- 5.90 nM. The most potent inhibitors 3g insert ignore into journalissuearticles values(Ki = 4.07 +/- 0.38 nM, hCA I);, 3c insert ignore into journalissuearticles values(Ki = 10.68 +/- 0.98 nM, hCA II);, and 3f insert ignore into journalissuearticles values(Ki = 8.91 +/- 1.65 nM, AChE); can be considered as lead compounds of this study with their promising bioactivity results. Secondary sulfonamides showed promising enzyme inhibitory effects on AChE while primary sulfonamide derivative was generally effective on hCA I and hCA II isoenzymes.
Keywords : Sulfonamide, benzamide, carbonic anhydrase, acetylcholinesterase, enzyme inhibition