Interplay Between Malaria, Crystalline Hemozoin Formation, and Antimalarial Drug Action and Design

Abstract

This review on the interplay between malaria, antimalarial drugs, and hemozoin crystals is directed, on one hand, to biologists and pharmaceutical chemists who wish to have a broader knowledge of the crystalline state related to malaria and, on the other hand, to crystallographers and physical chemists who wish to have a simple introduction to the disease and drugs employed against it. The call for this review is dictated by various considerations, not the least being the need for new antimalarial drugs, in view of developing parasitic resistance to the commonly used ones. The increasing spread of malaria is also due to several other contributing factors; besides climatic and environmental factors, the Anopheles mosquito has become increasingly resistant to insecticides and has adapted so as to avoid * To whom correspondence should be addressed. E-mail: (I.W.) isabelle.weissbuch@weizmann.ac.il or (L.L.) leslie.leiserowitz@weizmann.ac.il. The review represents the fruits, the offshoot, one may say, that may be reaped from the experience and knowledge gleaned from a collaborative effort, extending for more than a quarter of a century, on the design and use of auxiliaries for the control of crystal nucleation, morphology, and polymorphism, the structure determination of monoand multilayer films of amphiphilic molecules by grazing incidence synchrotron X-ray diffraction at the air-liquid interface, and computational studies of molecular interactions at interfaces and in the crystal bulk. These studies have been conducted in close collaboration with Meir Lahav and with other colleagues. Chem. Rev. 2008, 108, 4899–4914 4899