Design, synthesis, characterization, biological evaluation, and molecular docking studies of novel 1,2-aminopropanthiols substituted derivatives as selective carbonic anhydrase, acetylcholinesterase and α-glycosidase enzymes inhibitors

Abstract

In the article, various substituted derivatives of 1,2-aminopropanthiol (1a–g) have been prepared by a general and efficientmethod, in one-steps, starting fromavailable thiirane and aromatic amines (aniline, o-toluidine) as a convenient source of sulfur and nitrogen. The synthesized compounds were fully characterized by spectral and analytical data. Seven novel compounds are synthesized. The biochemical properties indicating their potential for constituting an anti-Alzheimer’s disease substance were also recorded revealing strong carbonic anhydrase I, and II, a-glycosidase, and acetylcholinesterase inhibitory effects. These synthesized novel 1,2-aminopropanthiols substituted derivatives (1a–g) were found to be effective inhibitors for the a-glycosidase, human carbonic anhydrase I and II, and acetylcholinesterase enzymes, with Ki values in the range of 11.47± 0.87–24.09±6.37 mM for a-glycosidase, 29.30±4.67-79.01±4.49mM for hCA I, 14.27±2.82-30.85±12.24mM for hCA II and 5.76±1.55–55.39±2.27 mMfor AChE, respectively. In the last step of this study,molecular docking calculationswere obtained in order to compare the biological activities of indicatedmolecules against the enzymes of acetylcholinesterase, butyrylcholinesterase and a-glycosidase.