There is an urgent need to develop new efficacious antimalarials to address the emerging drug-resistant clinical cases. Our previous phenotypic screening identified styrylquinoline as a promising antimalarial compound. To optimize lead scaffod, we herein report a detailed structure-activity relationship study of 2-arylvinylquinolines, leading to the discovery of potent, low nanomolar antiplasmodial compounds against a <i>P. falciparum</i> CQ-resistant Dd2 strain, with excellent selectivity profiles (RI &lt; 1 and SI &gt; 200). Several metabolically stable 2-arylvinylquinolines are identified as fast-acting agents that kill asexual blood stage parasites at the trophozoite phase, and the most promising compound also demonstrates transmission blocking potential. Additionally, the monophosphate salt of this compound exhibits excellent <i>in vivo</i> antimalarial efficacy in the murine model without noticeable toxicity. Thus, the 2-arylvinylquinolines represent a promising class of antimalarial drug leads

Synthesis, structure-activity relationship and antimalarial efficacy of 6-chloro-2-arylvinylquinolines

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.