Proguanil, also known as chloroguanide, is a synthetic antimalarial drug introduced in the 1940s after British researchers at Imperial Chemical Industries developed it during World War II to protect soldiers from malaria. A biguanide derivative, it acts through its active metabolite cycloguanil, which inhibits the parasite’s dihydrofolate reductase (DHFR) and disrupts DNA synthesis during early liver and blood stages of infection. Although it was initially effective as a standalone prophylactic, rising resistance in Plasmodium falciparum led to its adoption mainly in combination therapies, most notably with atovaquone in the 1990s—an innovation that greatly improved efficacy and remains widely used today for both malaria prevention and treatment.
