Malarial protease inhibitors: potential new chemotherapeutic agents.

The current limitations of malaria vaccine development, and the emergence and spread of insecticide-resistant vectors and drug-resistant parasites are major causes behind the re-emergence and severity of a worldwide malaria problem. A potential new target for antimalarial chemotherapy includes the malarial proteases that are required for erythrocytic invasion, egress and degradation of hemoglobin by parasites for its survival. Protease inhibitors must be highly potent and specific for parasite proteases to be recognized as biological tools. Screening, synthesis and evaluation studies have identified non-peptide derivatives that are able to kill parasites in vitro via protease inhibition. This review summarizes experimental evidence to support the rational design and development of protease inhibitors as potential new antimalarial drugs.