Reguera Rosa M, Díaz-González Rosario, Pérez-Pertejo Yolanda, Balaña-Fouce Rafael
Dpto. Farmacología y Toxicología (INTOXCAL), Universidad de León, Campus de Vegazana s/n, 24071 León, Spain.
Curr Drug Targets. 2008 Nov;9(11):966-78. doi: 10.2174/138945008786786118.
African and South American trypanosomes and leishmanias are unicellular protozoan parasites, forming part of the order Kinetoplastida. These ancient eukaryotes are causative agents of some of the most devastating neglected Tropical Diseases called trypanosomiasis and leishmaniasis. Despite the efforts to develop effective vaccines, immunoprophylaxis is not even a method of prevention of these diseases at present. Current antiprotozoal chemotherapy is often expensive, has side or toxic effects and it does not provide economic profits to the Pharmaceuticals, which have scant enthusiasm in R + D investments in this field. The surprising finding of unusual bi-subunit type IB DNA-topoisomerase in kinetoplastids adds a new promising drug target to antiprotozoal chemotherapy. The remarkable differences between trypanosomal and leishmanial DNA-topoisomerase IB with respect to the one in the mammalian hosts, have provided a new lead in the study of structural determinants that can be effectively targeted. This review provides an update on recent progress in research in kinetoplastid's topoisomerase IB as potential chemotherapeutic target against this group of parasitic diseases.
非洲和南美洲的锥虫及利什曼原虫是单细胞原生动物寄生虫，属于动质体目。这些古老的真核生物是一些最具毁灭性的被忽视热带病（称为锥虫病和利什曼病）的病原体。尽管人们努力研发有效的疫苗，但目前免疫预防甚至都不是预防这些疾病的一种方法。当前的抗原生动物化疗往往费用高昂，有副作用或毒性作用，而且对制药公司没有经济效益，制药公司对该领域的研发投资缺乏热情。在动质体中发现不寻常的双亚基IB型DNA拓扑异构酶这一惊人发现，为抗原生动物化疗增添了一个新的有前景的药物靶点。锥虫和利什曼原虫的DNA拓扑异构酶IB与哺乳动物宿主中的该酶存在显著差异，这为可有效靶向的结构决定因素的研究提供了新线索。本综述介绍了动质体拓扑异构酶IB作为针对这类寄生虫病的潜在化疗靶点的研究最新进展。
