Microtubule inhibitors as potential antimalarial agents

The Steering Committee on Drugs for Malaria (CHEMAL) of the UNDP/WorId Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDX) has identified tubulin as a potential drug target, but one that is not yet 'validated'. Several inhibitors of tubulins, the principal proteins of microtubules, are potent inhibitors of the development and multiplication of malarial parasites in culture and in vivo. However, most of these compounds are also inhibitors of mammalian cell proliferation. Here, Angus Bell reviews the structure and properties of microtubules, their roles in Plasmodium cells, and the effects of various microtubule inhibitors on the parasite. He argues that microtubule inhibitors are not equally toxic to all proliferating cells but, by virtue of differential tubulin binding, show selective toxicity that might allow their use as antimalarial drugs.