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Updated: Jun 9, 2026
08:31
Optimized Griess Reaction for UV-Vis and Naked-eye Determination of Anti-malarial Primaquine
Published on: October 11, 2019
Heme as trigger and target for trioxane-containing antimalarial drugs
1Palumed, 3 rue de l'Industrie, Z. I. Vic, 31320 Castanet-Tolosan, France. b.meunier@palumed.fr
Accounts of Chemical Research
|September 1, 2010
Summary
Heme is a critical target for antimalarial drugs like artemisinin. These drugs alkylate heme, forming toxic adducts that kill malaria parasites and show potential for anticancer therapies.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Parasitology
Background:
- Heme is essential for oxygen transport and enzymatic functions.
- Malaria parasites detoxify toxic heme by forming hemozoin.
- Heme's redox activity is central to its biological roles.
Purpose of the Study:
- To elucidate the mechanism of action of artemisinin and related antimalarial drugs.
- To investigate the role of heme as a drug target in malaria.
- To explore the potential of heme alkylation in anticancer drug development.
Main Methods:
- Studying the reaction mechanism between artemisinin and heme.
- Demonstrating heme alkylation in vivo using malaria-infected mice.
- Correlating antimalarial efficacy with heme alkylation ability of drug derivatives.
Main Results:
- Artemisinin and its derivatives alkylate heme, forming covalent adducts.
- Heme alkylation generates toxic, non-polymerizable heme derivatives.
- The peroxide bridge in artemisinin is crucial for its activity.
Conclusions:
- Heme acts as both the trigger and target for artemisinin's antimalarial activity.
- Heme alkylation is a key mechanism for peroxide-containing antimalarials.
- Targeting heme with endoperoxide compounds shows promise for anticancer drug discovery.
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