D'Annessa Ilda, Castelli Silvia, Desideri Alessandro
Department of Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, Rome 00133, Italy.
Mini Rev Med Chem. 2015;15(3):203-10. doi: 10.2174/138955751503150312120912.
Leishmaniasis affects more than 12 million people in 98 countries, the infection being caused by more than 20 species of protozoan parasites belonging to the genus Leishmania and spread by sandflies bite. Poor sanitary conditions, malnutrition, deforestation and urbanization increase the risk for leishmaniasis. Leishmaniasis is the only tropical disease treated with non-anti-leishmanial drugs, among which liposomal amphotericin B, a combination of pentavalent antimonials and paromomycin and miltefosine, that are highly toxic, represent the most used ones. Drug resistance is now widespread and the search for new molecular targets is open. Topoisomerase 1B, that controls the topological state of DNA and is essential for the parasites viability, has been detected as a promising target for anti-leishmaniasis therapy. The enzyme presents structural/functional differences with the human counterpart, making it unique among Eukarya. Here we review the structural features of this enzyme and the drugs that can be developed and used for this specific targeting.
利什曼病在98个国家影响着超过1200万人，该感染由20多种属于利什曼原虫属的原生动物寄生虫引起，并通过白蛉叮咬传播。卫生条件差、营养不良、森林砍伐和城市化增加了患利什曼病的风险。利什曼病是唯一用非抗利什曼药物治疗的热带疾病，其中脂质体两性霉素B、五价锑化合物与巴龙霉素的组合以及米替福新，这些药物毒性很大，是最常用的药物。耐药性现在很普遍，寻找新的分子靶点的工作正在进行。拓扑异构酶1B控制着DNA的拓扑状态，对寄生虫的生存能力至关重要，已被检测为抗利什曼病治疗的一个有希望的靶点。该酶与人类对应物存在结构/功能差异，使其在真核生物中独一无二。在这里，我们综述了这种酶的结构特征以及可开发和用于这种特异性靶向的药物。
