Yeast Sensors for Novel Drugs: Chloroquine and Others Revealed

Abstract

In this study the mitochondrion is regarded as a target to reveal compounds that may be used to combat various diseases. Consequently, the sexual structures of yeasts (with high mitochondrial activity) were identified as sensors to screen for various anti-mitochondrial drugs that may be toxic to humans and that are directed, amongst others, against fungal diseases and cancer. Strikingly, these sensors indicated that chloroquine is a potent pro-mitochondrial drug which stimulated yeast sexual reproduction. In addition, these sensors also showed that some Non-Steroidal Anti-Inflammatory drugs (NSAIDs), anti-malarial drugs, antifungal and anticancer drugs are anti-mitochondrial. These yeast sensor bio-assays may fast track studies aimed at discovering new drugs as well as their mechanisms and should now be further evaluated for selectivity towards anti-/ pro-mitochondrials, fertility drugs and contraceptives, using in vitro, in vivo, in silico and omics research.

Chloroquine, an Antifungal but Also a Fertility Drug

“…The plant pathogen Eremothecium ashbyi responded to sublethal CQ concentrations with increased (sexual) ascospore production. In addition, CQ stimulated ascospore release of Dipodascopsis uninucleata at nonlethal concentrations and, even more strikingly, enhanced the sexual reproductive stage of Lipomyces yamadae, even after it was preserved by prolonged subcultivation, causing a drastic decrease in sexual reproduction (2). This drug also revived the sexual stage of the yeast Scheffersomyces stipitis after it had presumably lost this ability after prolonged storage (unpublished data).…”