In Vitro Antimalarial Activity of Trichothecenes against Liver and Blood Stages of Plasmodium Species

J Nat Prod. 2024 Feb 23;87(2):315-321. doi: 10.1021/acs.jnatprod.3c01019.

Prakash T Parvatkar ¹, Steven P Maher ², Yingzhao Zhao ¹, Caitlin A Cooper ², Sagan T de Castro ², Julie Péneau ³, Amélie Vantaux ³, Benoît Witkowski ³, Dennis E Kyle ², Roman Manetsch ¹ ⁴ ⁵ ⁶

Affiliations

1 Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
2 Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia 30602, United States.
3 Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, 5 Boulevard Monivong, PO Box 983, Phnom Penh, 120 210, Cambodia.
4 Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, United States.
5 Center for Drug Discovery, Northeastern University, Boston, Massachusetts 02115, United States.
6 Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, Massachusetts 02115, United States.

PMID: 38262446 DOI: 10.1021/acs.jnatprod.3c01019

Abstract

Trichothecenes (TCNs) are a large group of tricyclic sesquiterpenoid mycotoxins that have intriguing structural features and remarkable biological activities. Herein, we focused on three TCNs (anguidine, verrucarin A, and verrucarol) and their ability to target both the blood and liver stages of Plasmodium species, the Parasite responsible for malaria. Anguidine and verrucarin A were found to be highly effective against the blood and liver stages of malaria, while verrucarol had no effect at the highest concentration tested. However, these compounds were also found to be cytotoxic and, thus, not selective, making them unsuitable for drug development. Nonetheless, they could be useful as chemical probes for protein synthesis inhibitors due to their direct impact on Parasite synthesis processes.

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