THC shows activity against cultured Plasmodium falciparum

Ana Carolina C de Sousa; Jill M Combrinck; Keletso Maepa; Timothy J Egan

doi:10.1016/j.bmcl.2021.128442

THC shows activity against cultured Plasmodium falciparum

Bioorg Med Chem Lett. 2021 Dec 15:54:128442. doi: 10.1016/j.bmcl.2021.128442. Epub 2021 Nov 8.

Authors

Ana Carolina C de Sousa¹, Jill M Combrinck², Keletso Maepa², Timothy J Egan³

Affiliations

¹ University of Cape Town, Department of Chemistry, Rondebosch 7701, South Africa. Electronic address: anacarolinacsousa@hotmail.com.
² University of Cape Town, Division of Pharmacology, Department of Medicine, Observatory 7925, South Africa.
³ University of Cape Town, Department of Chemistry, Rondebosch 7701, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa. Electronic address: timothy.egan@uct.ac.za.

PMID: 34763083
DOI: 10.1016/j.bmcl.2021.128442

Abstract

The FDA approved drug Dronabinol was identified in a previous study applying virtual screening using the haemozoin crystal as a target against malaria parasites. The active ingredient of dronabinol is synthetic tetrahydrocannabinol (THC), which is one of the major cannabinoids from Cannabis sativa. Traditional use of cannabis for malaria fever was reported in the world's oldest pharmacopoeia, dating to around 5000 years ago. In this research we report that THC inhibits β-haematin (synthetic haemozoin) and malaria parasite growth. Due the psychoactivity of THC, CBD, the other major naturally occurring cannabinoid that lacks the off-target psychoactive effects of THC, was also tested and inhibited β-haematin but showed only a mild antimalarial activity. To evaluate whether THC inhibit haemozoin formation, we performed a cellular haem fractionation assay that indicated that is not the likely mechanism of action. For the first time, the cannabinoid chemical structure is raised as a new chemical class to be further studied for malaria treatment, aiming to overcome the undesirable psychoactive effects of THC and optimize the antimalarial effects.

Keywords: Cannabinoids; Cannabis; Dronabinol; Haemozoin; Malaria; β-haematin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antimalarials / chemistry
Antimalarials / pharmacology*
Cannabis / chemistry
Dose-Response Relationship, Drug
Dronabinol / chemistry
Dronabinol / pharmacology*
HL-60 Cells
Hemeproteins / antagonists & inhibitors
Humans
Malaria / drug therapy*
Molecular Structure
Parasitic Sensitivity Tests
Plasmodium falciparum / drug effects*
Structure-Activity Relationship

Substances

Antimalarials
Hemeproteins
hemozoin
Dronabinol