Natural product inspired novel antimalarials with radical cure potential

Despite the increased attention on the eradication of malaria, prevention and treatment of the disease remain difficult due to i) the emerging resistance to the currently available antimalarials, including front-line artemisinin- based combination therapy (ACT), ii) the absence of a clinically effective vaccine, and iii) the spread of insecticide-resistant vectors. Therefore, there is an urgent and continuous need for safe, affordable and novel antimalarial drugs that can combat multiple stages of the parasite life cycle, with novel mechanism(s) of action to overcome the emerging drug resistance. A natural product inspired novel prodiginine chemotype with broad-spectrum antimalarial activity has been developed and the lead prodiginine candidate meets the aforementioned key requirements, such as 1) novel chemotype; 2) equally effective against a large panel of blood stage Plasmodium falciparum MDR parasites; 3) prevents liver stage infection with radical cure ability; 4) effective against sexual blood stage P. falciparum gametocytes; 5) highly likely operates by a novel mechanism of action; 6) optimal in vitro metabolic stability and in vivo PK profiles with rapid absorption, and long half-life; and 7) synthetically accessible with low-cost production. The proposed work in this application seeks to develop a novel antimalarial prodiginine drug that is potent against multiple stages of Plasmodia, with the potential to circumvent drug resistance, and prevent relapsing malaria infection.

Project details

Drug-based Strategies
Product Development

Apr 2023 — Mar 2028

$656,445

United States