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atovaquone + proguanil
- Development stage
- Approved
- Lead developer
- GSK
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Atovaquone + proguanil is a fixed-dose combination antimalarial medication used for both the treatment and prevention of malaria, particularly malaria caused by *Plasmodium falciparum*, including chloroquine-resistant strains. The combination contains two active ingredients with complementary mechanisms of action. Atovaquone selectively inhibits the malarial cytochrome bc1 complex in the parasite's mitochondrial electron transport chain, leading to collapse of mitochondrial membrane potential and indirect inhibition of dihydroorotate dehydrogenase—an enzyme essential for pyrimidine biosynthesis. Proguanil is metabolized to cycloguanil, which acts as a dihydrofolate reductase inhibitor and disrupts parasitic DNA synthesis. This dual mechanism enhances efficacy against malaria parasites[1][5][8]. The drug was originally developed by Glaxo Wellcome (now part of GSK) and is available as both branded (Malarone) and generic formulations[5].
- Brand names
- MalaroneMalarone Pediatric
- Other names
- atovaquone and proguanilatovaquone/proguanil
02
Targets
bc1 complex (Cytochrome bc1 complex (plasmodium))DHFR-TS (Bifunctional dihydrofolate reductase-thymidylate synthase)
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