Potent Antimalarial Activity of Two Arenes Linked with Triamine Designed To Have Multiple Interactions with Heme.

ABSTRACT: Based on the idea that compounds designed to exhibit high affinity for heme would block hemozoin formation, a critical heme-detoxification process for malarial parasites, we synthesized a series of compounds with two π-conjugated moieties at terminal amino groups of triamine. These compounds exhibited moderate to high antimalarial activities in vitro toward both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. In a P. berghei-infected mouse model, 3a and 12a showed potent antimalarial activities compared to artesunate, as well as a prolonged duration of antimalarial effect. We found a good correlation between protective activity against hemin degradation and antimalarial activity. Compounds 8b and 3a strongly inhibited

SUBMITTER: Sakata Y 

PROVIDER: S-EPMC6187406 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature