<i>Ex vivo</i> susceptibilities to ganaplacide and diversity in potential resistance mediators in Ugandan <i>Plasmodium falciparum</i> isolates.

ABSTRACT: Novel antimalarials are urgently needed to combat rising resistance to available drugs. The imidazolopiperazine ganaplacide is a promising drug candidate, but decreased susceptibility of laboratory strains has been linked to polymorphisms in the Plasmodium falciparum cyclic amine resistance locus (PfCARL), acetyl-CoA transporter (PfACT), and UDP-galactose transporter (PfUGT). To characterize parasites causing disease in Africa, we assessed ex vivo drug susceptibilities to ganaplacide in 750 P. falciparum isolates collected in Uganda from 2017 to 2023. Drug susceptibilities were assessed using a 72-hour SYBR Green growth inhibition assay. The median IC₅₀ for ganaplacide was 13.8 nM, but some isolates had up to 31-fold higher IC₅₀s (31/750 wi

SUBMITTER: Kreutzfeld O 

PROVIDER: S-EPMC11373204 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature