Jump to main content
Jump to site search


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

Publication details

The article was received on 11 Jul 2019, accepted on 03 Oct 2019 and first published on 08 Nov 2019


Article type: Research Article
DOI: 10.1039/C9MD00358D
Med. Chem. Commun., 2019, Advance Article

  •   Request permissions

    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, Advance Article , DOI: 10.1039/C9MD00358D

Search articles by author

Spotlight

Advertisements