Surolia Avadhesha, Ramya T N C, Ramya V, Surolia Namita
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
Biochem J. 2004 Nov 1;383(Pt. 3):401-12. doi: 10.1042/BJ20041051.
Malaria, a tropical disease caused by Plasmodium sp., has been haunting mankind for ages. Unsuccessful attempts to develop a vaccine, the emergence of resistance against the existing drugs and the increasing mortality rate all call for immediate strategies to treat it. Intense attempts are underway to develop potent analogues of the current antimalarials, as well as a search for novel drug targets in the parasite. The indispensability of apicoplast (plastid) to the survival of the parasite has attracted a lot of attention in the recent past. The present review describes the origin and the essentiality of this relict organelle to the parasite. We also show that among the apicoplast specific pathways, the fatty acid biosynthesis system is an attractive target, because its inhibition decimates the parasite swiftly unlike the 'delayed death' phenotype exhibited by the inhibition of the other apicoplast processes. As the enzymes of the fatty acid biosynthesis system are present as discrete entities, unlike those of the host, they are amenable to inhibition without impairing the operation of the host-specific pathway. The present review describes the role of these enzymes, the status of their molecular characterization and the current advancements in the area of developing inhibitors against each of the enzymes of the pathway.
疟疾是一种由疟原虫引起的热带疾病，长期以来一直困扰着人类。研发疫苗的尝试未获成功、对现有药物产生耐药性以及死亡率不断上升，都迫切需要立即采取治疗策略。目前正在大力研发现有抗疟药物的有效类似物，并在寄生虫中寻找新的药物靶点。近年来，顶质体（质体）对寄生虫生存的不可或缺性引起了广泛关注。本综述描述了这个残留细胞器的起源及其对寄生虫的重要性。我们还表明，在顶质体特异性途径中，脂肪酸生物合成系统是一个有吸引力的靶点，因为与抑制其他顶质体过程所表现出的“延迟死亡”表型不同，抑制该系统能迅速消灭寄生虫。由于脂肪酸生物合成系统的酶以离散实体形式存在，与宿主的酶不同，它们易于被抑制而不会损害宿主特异性途径的运作。本综述描述了这些酶的作用、它们的分子表征状况以及在开发针对该途径中每种酶的抑制剂领域的当前进展。
