Repositioning\nBrusatol as a Transmission Blocker of\nMalaria Parasites

Currently, primaquine is the only malaria transmission-blocking\ndrug recommended by the WHO. Recent efforts have highlighted the importance\nof discovering new agents that regulate malarial transmission, with\nparticular interest in agents that can be administered in a single\nlow dose, ideally with a discrete and <i>Plasmodium</i>-selective\nmechanism of action. Here, our team demonstrates an approach to identify\nmalaria transmission-blocking agents through a combination of <i>in vitro</i> screening and <i>in vivo</i> analyses.\nUsing a panel of natural products, our approach identified potent\ntransmission blockers, as illustrated by the discovery of the transmission-blocking\nefficacy of brusatol. As a member of a large family of biologically\nactive natural products, this discovery provides a critical next step\ntoward developing methods to rapidly identify quassinoids and related\nagents with valuable pharmacological therapeutic properties.