期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 57, 期 6, 页码 1043-1054出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkl104
关键词
malaria; antimalarials; folate; dihydrofolate reductase; dihydropteroate synthase
资金
- Wellcome Trust Funding Source: Medline
Chemotherapy remains the most important means of controlling malaria, one of the deadliest infectious parasitic diseases in the world. Antimalarial antifolates have been central for prophylaxis and treatment of malaria. This drug family was discovered in the 1940s, during the Second World War, and molecules that are currently in clinical use were discovered at that time. Since the 1940s, no new antimalarial antifolates have been developed that have reached Phase I/II stages. Limited work has been carried out to exploit the inhibition of the malaria folate pathway as a means of discovering new drugs. In this review, work carried out on antimalarial antifolates since the 1940s up to the present time is discussed in terms of discovery, clinical use, mode of action and mechanism of resistance. New concepts have been presented to improve antimalarial antifolate in vivo efficacy and to identify potent new antifolate agents.
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