Recent Advances in the Discovery of Haem-Targeting Drugs for Malaria and Schistosomiasis

Molecules

Katherine A. de Villiers¹ 

[1]University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa

关键词: haem;    haemozoin;    high-throughput screening;    rational drug design;   

DOI  :  10.3390/molecules14082868

来源: mdpi

【 摘 要 】

Haem is believed to be the target of some of the historically most important antimalarial drugs, most notably chloroquine. This target is almost ideal as haem is host-derived and the process targeted, haemozoin formation, is a physico-chemical process with no equivalent in the host. The result is that the target remains viable despite resistance to current drugs, which arises from mutations in parasite membrane transport proteins. Recent advances in high-throughput screening methods, together with a better understanding of the interaction of existing drugs with this target, have created new prospects for discovering novel haem-targeting chemotypes and for target-based structural design of new drugs. Finally, the discovery that Schistosoma mansoni also produces haemozoin suggests that new drugs of this type may be chemotherapeutic not only for malaria, but also for schistosomiasis. These recent developments in the literature are reviewed.

【 授权许可】

CC BY   
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.