Optimization of antimalarials targeting multiple life stages of the parasite

The malaria parasite is one of the most deadly eukaryotic pathogens and more than 40% of the world’s population is at risk of contracting malaria. Due to growing resistance to currently available medications, there is a pressing medical need for new drugs to prevent and treat malaria infection.These compounds were identified using a combination of atomic property field-based virtual ligand screening (VLS) of a library of 5 million publicly available compounds and synthetic chemistry campaigns. Although 2a and (R)-3a bear a structural resemblance to MMV008138 and kill asexual blood-stages, their mechanism of action is independent of the apicoplast.

The ancillary goal of this proposal is to develop structure-activity relationships (SAR) for the P. falciparum gametocytocidal potency and P. berghei liver-stage potency of these two series, and to determine consensus pharmacophores for multi-stage activities (asexual blood-stage potencies plus gametocytocidal and/or liver-stage potencies). Efficacious compounds identified in this way will thus be well-positioned for further preclinical development.

NIH project details

Drug-based Strategies
Product Development

Aug 2021 — Jul 2026

$3.6M

United States