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 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, α-glycosidase, and acetylcholinesterase inhibitory effects. These synthesized novel 1,2-aminopropanthiols substituted derivatives (1a–g) were found to be effective inhibitors for the α-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 µM for α-glycosidase, 29.30 ± 4.67-79.01 ± 4.49 µM for hCA I, 14.27 ± 2.82-30.85 ± 12.24 µM for hCA II and 5.76 ± 1.55–55.39 ± 2.27 µM 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 α-glycosidase.

Communicated by Ramaswamy H. Sarma

Graphical Abstract

Keywords:

• Thiirane
• aniline
• 1,2-aminopropanthiol
• enzyme inhibition
• molecular docking

Acknowledgements

This research was made possible by TUBITAK ULAKBIM, High Performance and Grid Computing Center (TR-Grid e-Infrastructure). S. Alwasel would like to extend his sincere appreciation to the Researchers Supporting Project (RSP-2019/59), King Saud University, Saudi Arabia, for support. This work was carried out with the support of the Science Development Fund under the President of Azerbaijan Republic-EIF/GAM-4-BGM-GIN-2017-3(29)-19/05/4-M-07.

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

This work is supported by the Scientific Research Project Fund of Sivas Cumhuriyet University under the project number RGD-020.