A plant-derived morphinan as a novel lead compound active against malaria liver stages.

ABSTRACT:

Background

The global spread of multidrug-resistant malaria parasites has led to an urgent need for new chemotherapeutic agents. Drug discovery is primarily directed to the asexual blood stages, and few drugs that are effective against the obligatory liver stages, from which the pathogenic blood infection is initiated, have become available since primaquine was deployed in the 1950s.

Methods and findings

Using bioassay-guided fractionation based on the parasite's hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a plant traditionally used against malaria in Madagascar. This compound and readily obtained semisynthetic derivatives were tested for inhibitory activity against liver stage development in vitro (P. falciparum and P. yoelii) and in vivo (P.

SUBMITTER: Carraz M 

PROVIDER: S-EPMC1716192 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature