Selective Metal Chelation by a Thiosemicarbazone Derivative Interferes with Mitochondrial Respiration and Ribosome Biogenesis in Candida albicans
Ximeng Duan, Zhiyu Xie, Liying Ma, Xueyang Jin, Ming Zhang, Yuliang Xu, Yue Liu, Hong‐Xiang Lou, Wenqiang Chang
Abstract
The increasing incidence of fungal infections and resistance to existing antifungals call for the development of broad-spectrum antifungals with novel mechanisms of action. In this study, we demonstrate that a thiosemicarbazone derivative 19ak selectively inhibits mitochondrial respiration mainly by retarding mitochondrial respiratory chain complex I activity through iron chelation and inhibits ribosome biogenesis mainly by disrupting intracellular zinc homeostasis in C. albicans .
Topics & Concepts
Candida albicansMitochondrial respiratory chainIntracellularBiochemistryBiologyMitochondrionRespiratory chainAzoleAntifungal drugCorpus albicansChemistryMicrobiologyAntifungalTrace Elements in HealthAntifungal resistance and susceptibilityParasitic Infections and Diagnostics