Cycloguanil is a dihydrofolate reductase inhibitor,[1] and is a metabolite of the antimalarial drug proguanil; its formation in vivo has been thought to be primarily responsible for the antimalarial activity of proguanil.[2] However, more recent work has indicated that, while proguanil is synergistic with the drug atovaquone (as in the combination Malarone), cycloguanil is in fact antagonistic to the effects of atovaquone, suggesting that, unlike cycloguanil, proguanil may have an alternative mechanism of antimalarial action besides dihydrofolate reductase inhibition.[3]