Jump to main content
Jump to site search

Issue 12, 2019
Previous Article Next Article

Synthesis of new lophine–carbohydrate hybrids as cholinesterase inhibitors: cytotoxicity evaluation and molecular modeling

Author affiliations

Abstract

In this study, we synthesized nine novel hybrids derived from D-xylose, D-ribose, and D-galactose sugars connected by a methylene chain with lophine. The compounds were synthesized by a four-component reaction to afford the substituted imidazole moiety, followed by the displacement reaction between sugar derivatives with an appropriate N-alkylamino-lophine. All the compounds were found to be the potent and selective inhibitors of BuChE activity in mouse serum, with compound 9a (a D-galactose derivative) being the most potent inhibitor (IC50 = 0.17 μM). According to the molecular modeling results, all the compounds indicated that the lophine moiety existed at the bottom of the BuChE cavity and formed a T-stacking interaction with Trp231, a residue accessible exclusively in the BuChE cavity. Noteworthily, only one compound exhibited activity against AChE (8b; IC50 = 2.75 μM). Moreover, the in silico ADME predictions indicated that all the hybrids formulated in this study were drug-likely, orally available, and able to reach the CNS. Further, in vitro studies demonstrated that the two most potent compounds against BuChE (8b and 9a) had no cytotoxic effects in the Vero (kidney), HepG2 (hepatic), and C6 (astroglial) cell lines.

Graphical abstract: Synthesis of new lophine–carbohydrate hybrids as cholinesterase inhibitors: cytotoxicity evaluation and molecular modeling

Back to tab navigation

Supplementary files

Article information


Submitted
11 Jul 2019
Accepted
03 Oct 2019
First published
08 Nov 2019

Med. Chem. Commun., 2019,10, 2089-2101
Article type
Research Article

Synthesis of new lophine–carbohydrate hybrids as cholinesterase inhibitors: cytotoxicity evaluation and molecular modeling

J. P. B. Lopes, L. Silva, M. A. Ceschi, D. S. Lüdtke, A. R. Zimmer, T. C. Ruaro, R. F. Dantas, C. M. C. de Salles, F. P. Silva-Jr, M. R. Senger, G. Barbosa, L. M. Lima, I. A. Guedes and L. E. Dardenne, Med. Chem. Commun., 2019, 10, 2089
DOI: 10.1039/C9MD00358D

Search articles by author

Spotlight

Advertisements