Polonio Tilman, Efferth Thomas
Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany.
Int J Mol Med. 2008 Sep;22(3):277-86.
Epidemics of fatal visceral leishmaniasis caused by the intracellular protozoan Leishmania are a severe public health problem in tropical and subtropical regions of the world. One major drawback in the treatment of leishmaniasis is the emergence of resistance to current chemotherapeutics. Leishmanicidals have to be administered in low doses since commonly used drugs exhibit severe side effects, and hence drug resistance can appear rapidly. Since, to date, vaccination approaches have failed to enter clinical trials, chemotherapy based on small molecules is temporarily the exclusive treatment strategy. There is an urgent need for adding novel drugs with improved features to the pool of current chemotherapeutics. Many compounds derived from natural sources have pharmacological activities and may, thus, be of potential utility in drug development and biomedical research. Natural products, primarily plant-derived substances of diverse structural classes, have been described in the literature showing anti-leishmanial properties. In this review we provide a brief overview of the current treatment and the active principles of established drugs. Furthermore, we focus on the mechanisms of drug resistance and natural products that are promising leads for the development of novel chemotherapeutics.
由细胞内原生动物利什曼原虫引起的致命内脏利什曼病的流行是世界热带和亚热带地区严重的公共卫生问题。利什曼病治疗中的一个主要缺陷是对当前化疗药物产生耐药性。由于常用药物有严重的副作用，杀利什曼剂必须低剂量给药，因此耐药性可能迅速出现。由于迄今为止，疫苗接种方法未能进入临床试验，基于小分子的化疗暂时是唯一的治疗策略。迫切需要在现有的化疗药物库中增加具有改进特性的新药。许多天然来源的化合物具有药理活性，因此可能在药物开发和生物医学研究中具有潜在用途。文献中描述了天然产物，主要是来自不同结构类别的植物源物质，具有抗利什曼原虫特性。在这篇综述中，我们简要概述了当前的治疗方法和现有药物的活性成分。此外，我们关注耐药机制以及有望成为新型化疗药物开发先导的天然产物。
