Deciphering the Biological Activities of Antifungal Agents with Chemical Probes

Abstract

The growing number of fungal infections caused by pathogens resistant to one or more classes of antifungal drugs emphasizes the threat that these microorganisms pose to animal and human health and global food security. Open questions remain regarding the mechanisms of action of the limited repertoire of antifungal agents, making it challenging to rationally develop more efficacious therapeutics. In recent years, the use of chemical biology approaches has resolved some of these questions and has provided new promising concepts to guide the design of antifungal agents. By focusing on examples from studies carried out in recent years, this minireview describes the key roles that probes based on antifungal agents and their derivatives have played in uncovering details about their activities, in detecting resistance, and in characterizing the interactions between these agents and their targets.

Poacic Acid, a Plant-Derived Stilbenoid, Augments Cell Wall Chitin Production, but Its Antifungal Activity Is Hindered by This Polysaccharide and by Fungal Essential Metals

“…Surprisingly, despite the high molecular similarity with PA, experimental evidence suggests that their mechanisms of action are fundamentally different. Morphological profiling of yeast cells treated with poacidiene implied that poacidiene impacts DNA damage response and not the yeast cell wall integrity, which was also supported by cell morphology and genetic analysis. , To shed light on the biological activities of PA and to examine its value as a cell-wall-directing agent, in this study, we investigated the mode of action of this natural stilbenoid and its synthetic derivatives, revealing new insights on its unique effects on yeast cells.…”