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

In the article, various substituted derivatives of 1,2-aminopropanthiol (1a-g) have been prepared by a general and efficient method, in one-steps, starting from available 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, alpha-glycosidase, and acetylcholinesterase inhibitory effects. These synthesized novel 1,2-aminopropanthiols substituted derivatives (1a-g) were found to be effective inhibitors for the alpha-glycosidase, human carbonic anhydrase I and II, and acetylcholinesterase enzymes, with K(i)values in the range of 11.47 +/- 0.87-24.09 +/- 6.37 mu M for alpha-glycosidase, 29.30 +/- 4.67-79.01 +/- 4.49 mu M for hCA I, 14.27 +/- 2.82-30.85 +/- 12.24 mu M for hCA II and 5.76 +/- 1.55-55.39 +/- 2.27 mu M for AChE, respectively. In the last step of this study, molecular docking calculations were obtained in order to compare the biological activities of indicated molecules against the enzymes of acetylcholinesterase, butyrylcholinesterase and alpha-glycosidase. Communicated by Ramaswamy H. Sarma

Automated summary

The article describes the synthesis and characterization of various substituted derivatives of 1,2-aminopropanthiol. These compounds exhibit inhibitory effects on enzymes including carbonic anhydrase and acetylcholinesterase, indicating their potential as anti-Alzheimer's disease substances.