Proguanil antimalarial actions

Soon after the Second World War (1943), a large number of compounds were synthesized and tested for antimalarial actions, and these eventually gave birth to a host of potent drugs like, chloroquine, proguanil, comoquine and amodiaquine, etc. 

Srivastava IK, Vaiefya AB. A mechanism for the S3fnergistic antimalarial action of atovaquone and proguanil. Antimicrob Agents Chemother (1999) 43,1334-9. 

Different antimalarials selectively kill the parasite s different developmental forms. The mechanism of action is known for some of them pyrimethamine and dapsone inhibit dihydrofolate reductase (p. 273), as does chlorguanide (proguanil) via its active metabolite. The sulfonamide sulfadoxine inhibits synthesis of dihydrofolic acid (p. 272). Chlo-roquine and quinine accumulate within the acidic vacuoles of blood schizonts and inhibit polymerization of heme, the latter substance being toxic for the schizonts. 

The mechanism of the antimalarial activity of proguanil or chlorproguanil is unknown. Proguanil as the biguanide accentuates the mitochondrial membrane-potential-collapsing action of ato-vaquone against P. falciparum but displays no such activity by itself (see Atovaquone, above). 

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