Antimalarial Drug Discovery: From Quinine to the Most Recent Promising Clinical Drug Candidates

Malaria is a tropical threatening disease caused by Plasmodium parasites, resulting in 409,000 deaths in 2019. The delay of mortality and morbidity has been compounded by the widespread of drug resistant parasites from Southeast Asia since two decades. The emergence of artemisinin-resistant Plasmodium in Africa, where most cases are accounted, highlights the urgent need for new medicines. In this effort, the World Health Organization and Medicines for Malaria Venture joined to define clear goals for novel therapies and characterized the target candidate profile. This ongoing search for new treatments is based on imperative labor in medicinal chemistry which is summarized here with particular attention to hit-to-lead optimizations, key properties, and modes of action of these novel antimalarial drugs. This review, after presenting the current antimalarial chemotherapy, from quinine to the latest marketed drugs, focuses in particular on recent advances of the most promising antimalarial candidates in clinical and preclinical phases.

Automated summary

Malaria is a tropical disease caused by Plasmodium parasites, resulting in 409,000 deaths in 2019. The spread of drug resistant parasites from Southeast Asia has further complicated the mortality and morbidity. The emergence of artemisinin-resistant Plasmodium in Africa, where most cases occur, has highlighted the urgent need for new medicines. This review focuses on the ongoing search for new antimalarial drugs, particularly in terms of medicinal chemistry and the development of promising candidates in clinical and preclinical phases.