Proguanil

Description: Proguanil, also known as chlorguanide and chloroguanide, is a orally available medication used to treat and prevent malaria. It is an antimalarial prodrug that is metabolized to the active metabolite cycloguanil, a dihydrofolate reductase (DHFR) inhibitor. It is often used together with chloroquine or atovaquone. When used with chloroquine the combination will treat mild chloroquine resistant malaria. When used alone, proguanil functions as a prodrug. Its active metabolite, cycloguanil, is an inhibitor of dihydrofolate reductase (DHFR). Although both mammals and parasites produce DHFR, cycloguanil's inhibitory activity is specific for parasitic DHFR. This enzyme is a critical component of the folic acid cycle. Inhibition of DHFR prevents the parasite from recycling dihydrofolate back to tetrahydrofolate (THF). THF is required for DNA synthesis, amino acid synthesis, and methylation; thus, DHFR inhibition shuts down these processes.

References: Vet Parasitol. 2013 Nov 8; 197(3-4):527-33; J Pharmacol Exp Ther. 2014 Dec; 351(3):674-84.

Related CAS#: 637-32-1 (HCl salt)