Targeting fungal virulence factor by small molecules: Structure-based discovery of novel secreted aspartic protease 2 (SAP2) inhibitors.

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Targeting fungal virulence factor by small molecules: Structure-based discovery of novel secreted aspartic protease 2 (SAP2) inhibitors.

Eur J Med Chem. 2020 Jun 21;201:112515

Authors: Li C, Liu Y, Wu S, Han G, Tu J, Dong G, Liu N, Sheng C

Abstract
Secreted aspartic protease 2 (SAP2), a kind of virulence factor, is an emerging new antifungal target. Using docking-based virtual screening and structure-based inhibitor design, a series of novel SAP2 inhibitors were successfully identified. Among them, indolone derivative 24a showed potent SAP2 inhibitory activity (IC50 = 0.92 μM). It blocked fungi biofilm and hypha formation by down-regulating the expression of genes SAP2, ECE1, ALS3 and EFG1. As a virulence factor inhibitor, compound 24a was inactive in vitro and showed potent in vivo efficacy in a murine model of invasive candidiasis. It represents a promising lead compound for the discovery of novel antifungal agents.

PMID: 32623209 [PubMed - as supplied by publisher]