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首页> 美国政府科技报告 >Anti-Malarial Effects of the Anti-Tubulin Herbicide Trifluralin: Studies withPlasmodium falciparum
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Anti-Malarial Effects of the Anti-Tubulin Herbicide Trifluralin: Studies withPlasmodium falciparum

机译：抗微管蛋白除草剂氟乐灵的抗疟疾作用：与恶性疟原虫的研究

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摘要

Tubulin is the major constituent protein of microtubules, which play a criticalrole in cellular processes like maintenance of cell shape and motility, cell division, differentiation, and maturation. The dinitroaniline herbicide, trifluralin (TF), which has the unique property of binding selectively to plant and algal tubulin, but not to animal tubulin, was recently shown to inhibit both proliferation and differentiation of the plant-like parasitic protozoan, Leishmania mexicana amazonensis. Since the inhibitory effects of TF were shown to be due to its specific binding to leishmanial tubulin and not to host tubulin, we have exploited the selective tubulin-binding property of TF to examine the potential antimalarial effects of this compound. TF, at 1-5 x 10(exp 6) M, inhibited (> 98%) the growth and differentiation of Plasmodium falciparum (the most virulent form of human malaria) in culture. Furthermore, there was complete inhibition of in vitro exflagellation of mature microgametocytes (a process which normally occurs in the mid-gut of the mosquito following an infective blood meal), after a 2 hr incubation with TF concentration as low as 10(exp 8) M. In addition, ultrastructural studies revealed complete dissolution of the subpellicular microtubule complex of mature gametocytes when treated with 10(exp 6) M TF for 2 hr at 37 deg C, indicating binding of the drug to malaria tubulin. Of particular relevance to this study, the addition of 5 x 10(exp 6) M TF to a gametocyte-infected blood meal of mosquitoes, completely inhibited the sexual development of the parasite in the mosquito midgut. Moreover, treatment of early stage gametocyte cultures (Stages II and M) with 5 x 10(exp 6) M TF. blocked the in vitro development of exflagellation-competent mature gametocytes.

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