DefinePK

Abstract

Malaria is a significant worldwide health challenge as evident from the latest WHO malaria report. The disease, predominantly caused by Plasmodium falciparum, has become progressively challenging to manage due to the establishment and dissemination of resistance to existing antimalarial medications, including chloroquine, sulfadoxine-pyrimethamine, and artemisinin-based therapies. The increasing resistance underscores the pressing necessity to identify and formulate new antimalarial agents with innovative modes of action.  A promising research avenue focuses on targeting parasite-specific enzymes critical for survival, especially cysteine proteases. Falcipain-2, a papain-like cysteine protease, is crucial for hemoglobin breakdown throughout the intraerythrocytic phase of the parasite's life cycle.  Recent research has revealed many falcipain-2 inhibitors, such as vinyl sulfones, artemisinin hybrids, quinoline-based compounds, and suramin analogues, many of which exhibit significant antiparasitic efficacy and the ability to surmount resistance. This review highlights the potential of falcipain-2 as a target for antimalarial drug development. Continued research in this domain may result in the identification of efficacious treatments for drug-resistant malaria.