Benzimidazole Derivatives Are Potent against Multiple Life Cycle Stages of Malaria Parasites.

The continued emergence of resistance to front-line antimalarial treatments is of great concern. Therefore, new compounds that potentially have a novel target in various developmental stages of parasites are needed to treat patients and halt the spread of malaria. Here, several benzimidazole derivatives were screened for activity against the symptom-causing intraerythrocytic asexual blood stages and the transmissible gametocyte stages of . Submicromolar activity was obtained for 54 compounds against asexual blood stage parasites with 6 potent at IC < 100 nM while not displaying any marked toxicity against mammalian cells. Nanomolar potency was also observed against gametocytes with two compounds active against early stage gametocytes and two compounds active against late-stage gametocytes. The transmission-blocking potential of the latter was confirmed as they could prevent male gamete exflagellation and the lead compound reduced transmission by 72% in an mosquito feeding model. These compounds therefore have activity against multiple stages of parasites with potential for differential targets.