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Scaffold diversity for enhanced activity of glycosylated inhibitors of fungal adhesion

Version 2 2024-06-04, 02:36
Version 1 2020-09-24, 15:50
journal contribution
posted on 2020-08-17, 00:00 authored by Harlei Martin, Tara Somers, Mathew Dwyer, Ryan Robson, Fred PfefferFred Pfeffer, Ragnar Bjornsson, Tobias Krämer, Kevin Kavanagh, Trinidad Velasco-Torrijos
Candida albicans is one of the most prevalent fungal pathogens involved in hospital acquired infections. It binds to glycans at the surface of epithelial cells and initiates infection. This process can be blocked by synthetic carbohydrates that mimic the structure of cell surface glycans. Herein we report the evaluation of a series of divalent glycosides featuring aromatic (benzene, squaramide) and bicyclic aliphatic (norbornene) scaffolds, with the latter being the first examples of their kind as small molecule anti-adhesion glycoconjugates. Galactosides 1 and 6, built on an aromatic core, were most efficient inhibitors of adhesion of C. albicans to buccal epithelial cells, displacing up to 36% and 48%, respectively, of yeast already attached to epithelial cells at 138 μM. Remarkably, cis-endo-norbornene 21 performed comparably to benzene-core derivatives. Conformational analysis reveals a preference for compounds 1 and 21 to adopt folded conformations. These results highlight the potential of norbornenes as a new class of aliphatic scaffolds for the synthesis of anti-adhesion compounds.

History

Journal

RSC Medicinal Chemistry

Volume

11

Issue

12

Season

December 2020

Pagination

1386 - 1401

Publisher

Royal Society of Chemistry (RSC)

Location

Cambridge, Eng.

eISSN

2632-8682

Language

eng

Publication classification

C Journal article; C1 Refereed article in a scholarly journal

Copyright notice

2020, Royal Society of Chemistry