The Nonartemisinin Sesquiterpene Lactones Parthenin and Parthenolide Block Plasmodium falciparum Sexual Stage Transmission

Antimicrobial Agents and Chemotherapy
Jared N BalaichR R Dinglasan

Abstract

Parthenin and parthenolide are natural products that are closely related in structure to artemisinin, which is also a sesquiterpene lactone (SQL) and one of the most important antimalarial drugs available. Parthenin, like artemisinin, has an effect onPlasmodiumblood stage development. We extended the evaluation of parthenin as a potential therapeutic for the transmissible stages ofPlasmodium falciparumas it transitions between human and mosquito, with the aim of gaining potential mechanistic insight into the inhibitory activity of this compound. We posited that if parthenin targets different biological pathways in the parasite, this in turn could pave the way for the development of druggable compounds that could prevent the spread of artemisinin-resistant parasites. We examined parthenin's effect on male gamete activation and the ookinete-to-oocyst transition in the mosquito as well as on stage V gametocytes that are present in peripheral blood. Parthenin arrested parasite development for each of the stages tested. The broad inhibitory properties of parthenin on the evaluated parasite stages may suggest different mechanisms of action between parthenin and artemisinin. Parthenin's cytotoxicity notwithstanding, its demonstrated a...Continue Reading

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Citations

Dec 7, 2019·Malaria Journal·Nasir Tajuddeen, Fanie R Van Heerden
Sep 23, 2020·Pharmaceuticals·Phanankosi MoyoLyn-Marié Birkholtz
May 3, 2019·Pest Management Science·Baldwyn Torto
Oct 5, 2017·Journal of Natural Products·Carmina SirignanoOrazio Taglialatela-Scafati

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