Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\'Alcontres, 31 - 98166 Messina, Italy.
Curr Med Chem. 2022;29(17):2952-2978. doi: 10.2174/0929867328666210810125309.
Despite the countless efforts made in the last decades, malaria and neglected tropical diseases remain a high-impact health problem in developing countries. Malaria is one of the most severe parasitic diseases, with over 200 million cases and 400,000 deaths in 2019. Parasitic diseases caused by trypanosomatidae, namely Human African Trypanosomiasis, Chagas disease, and leishmaniasis, register the highest rates of mortality amongst all the neglected tropical diseases. In this scenario, chemotherapy remains the first strategy, which aims to control and eliminate these diseases. However, the use of outdated, unsafe, and poorly effective drugs, together with the onset of resistance, prompted the researchers to identify new and valid targets. The innovative idea, aimed at the development of multi-target ligands addressing two different targets playing key roles in parasite survival, could represent a valuable strategy. Thanks to this approach, the wellknown limitations characterizing the antiparasitic drugs, such as toxicity, rapid resistance onset and narrow spectrum of action, could be overcome. In this review, we now describe the most recent multi-target ligands endowed with antiparasitic effects reported in the literature, focusing our attention on their binding with the targets, inhibitory activities, and potential therapeutic applications.
尽管在过去几十年中付出了无数努力，但疟疾和被忽视的热带病仍然是发展中国家的一个重大健康问题。疟疾是最严重的寄生虫病之一，2019 年有超过 2 亿例病例和 40 万人死亡。由动基体目寄生虫引起的寄生虫病，即非洲人类锥虫病、恰加斯病和利什曼病，在所有被忽视的热带病中死亡率最高。在这种情况下，化疗仍然是首要策略，旨在控制和消除这些疾病。然而，由于使用过时、不安全且效果不佳的药物，以及耐药性的出现，促使研究人员寻找新的有效靶点。旨在开发针对两种在寄生虫生存中起关键作用的不同靶标具有多靶点配体的创新理念，可能是一种有价值的策略。通过这种方法，可以克服抗寄生虫药物的已知局限性，例如毒性、快速耐药性和作用谱狭窄。在这篇综述中，我们现在描述了文献中报道的具有抗寄生虫作用的最新多靶点配体，重点关注它们与靶标的结合、抑制活性和潜在的治疗应用。
