When used alone,<unk>  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.<unk>  displays synergism when used in combination with the antimalarial atovaquone. This mechanism of action differs from when<unk>  was used as a singular agent. In this case, it is not thought to function as a DHFR inhibitor. The addition of<unk>  has shown to reduce resistance to atovaquone and increase the ability of atovaquone to trigger a mitochondrial apoptotic cascade. This is commonly referred to as "collapse of the mitochondrial membrane potential."<unk>  lowers the effective concentration of atovaquone needed to increase permeability of the mitochondrial membrane.
Proguanil
Temgicoluril
Artemether
Quinine
Tiaprofenic acid
Fursultiamine
Gadobenic acid
Trenbolone hexahydrobenzylcarbonate