Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale T. Michel 11, 15121, Alessandria, Italy.
Universidad de Navarra, Instituto de Salud Tropical, Departamento de Química Orgánica y Farmacéutica, Campus Universitario, 31008, Pamplona, Spain.
Eur J Med Chem. 2018 Jul 15;155:459-482. doi: 10.1016/j.ejmech.2018.05.044. Epub 2018 Jun 1.
The development of safe and affordable antiparasitic agents effective against neglected tropical diseases is a big challenge of the drug discovery. The drugs currently employed have limitations such as poor efficacy, drug resistance or side effects. Thus, the search for new promising drugs is more and more crucial. Metal complexes and, in particular, organometallic compounds may expand the list of the drug candidates due to the peculiar attributes that the presence of the metal core add to the organic fragment (e.g., redox and structural features, ability to interact with DNA or protein targets, etc.). To date, most organometallic compounds tested as anti-neglected tropical diseases are based on similarities or activity of the organic ligands against other diseases or parasites and/or consist in modification of existing drugs combining the features of the metal moiety and the organic ligands. This review focuses on recent studies (2012-2017) on organometallic compounds in treating kinetoplastid-caused diseases such as Human African trypanosomiasis, Chagas disease and leishmaniasis. This field of research, however, still lacks exhaustive studies to identify of parasitic targets and quantitative structure-activity relationships for a rational drug design.
安全且负担得起的抗寄生虫药物的开发对于治疗被忽视的热带病是一个巨大的挑战。目前使用的药物存在疗效差、耐药性或副作用等问题。因此，寻找新的有前途的药物变得越来越重要。金属配合物，特别是有机金属化合物，由于金属核的存在为有机片段增加了独特的属性（例如，氧化还原和结构特征，与 DNA 或蛋白质靶标相互作用的能力等），可能会扩大候选药物的范围。迄今为止，大多数作为抗被忽视的热带病的测试的有机金属化合物基于对其他疾病或寄生虫的有机配体的相似性或活性，或者是通过将金属部分和有机配体的特性结合起来来修饰现有的药物。这篇综述重点介绍了 2012 年至 2017 年期间在治疗原生动物引起的疾病（如人类非洲锥虫病、恰加斯病和利什曼病）方面的有机金属化合物的最新研究进展。然而，这一研究领域仍缺乏详尽的研究，以确定寄生虫靶标和定量构效关系，从而进行合理的药物设计。
