Abstract
Researchers at the University of Central Florida have developed potent compounds for fighting chloroquine-resistant malaria-causing parasites. The low nanomolar compounds were effective against chloroquine-resistant Dd2 strains of Plasmodium falciparum parasites in vitro and completely cured malaria infection in vivo. The Plasmodium falciparum parasite has developed resistance to most antimalarial treatments, including chloroquine and artemisinin-based combination treatments (ACTs). Additionally, the high cost of ACTs prevents their broad use in low-income malaria-endemic countries and the loss of efficacy of frontline ACTs to the resistant malaria strains underscore the need to boost global malaria eradication efforts.
The UCF invention comprises compounds and pharmaceutical compositions that exhibit antiplasmodium potency against chloroquine-resistant (Dd2) strains of P. falciparum. For example, the most active compounds exhibit an IC50 = 15nM. Also included in the invention are methods of treating or preventing malaria using the antimalarial compounds.
Technical Details
UCF researchers identified several metabolically stable 2-arylvinylquinolines as fast-acting antimalarial agents that kill asexual blood-stage parasites at the trophozoite phase. The compounds show excellent selectivity profiles (RI < 1 and SI > 200). Additionally, the lead compound demonstrates transmission-blocking potential. In murine models, it exhibits exceptional in vivo antimalarial efficacy with 100% reduction of parasitemia without noticeable toxicity. Thus, the 2-arylvinylquinolines represent a promising class of compounds for the development of new antimalarial treatments.
Partnering Opportunity
The research team is seeking partners for licensing and/or research collaboration.
Stage of Development
Murine malaria model.
Benefit
Compounds exhibit antimalarial efficacy, high selectivity, and metabolic stability No noticeable toxicity in murine modelsOffers promising solutions for combatting drug-resistant, malaria-causing parasitesMarket Application
Antimalarial drugs and malaria therapyPublications
Synthesis,
Structure–Activity Relationship, and Antimalarial Efficacy of
6-Chloro-2-arylvinylquinolines, J Med Chem. 2020 Oct 22; 63(20):
11756–11785.
