Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission.

ABSTRACT: Cyclic nucleotide-dependent phosphodiesterases (PDEs) play essential roles in regulating the malaria parasite life cycle, suggesting that they may be promising antimalarial drug targets. PDE inhibitors are used safely to treat a range of noninfectious human disorders. Here, we report three subseries of fast-acting and potent Plasmodium falciparum PDEβ inhibitors that block asexual blood-stage parasite development and that are also active against human clinical isolates. Two of the inhibitor subseries also have potent transmission-blocking activity by targeting PDEs expressed during sexual parasite development. In vitro drug selection experiments generated parasites with moderately reduced susceptibility to the inhibitors. Whole-genome sequencing of these parasites detected no mutati

SUBMITTER: Gomez-Gonzalez PJ 

PROVIDER: S-EPMC11623267 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature