Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
Int J Parasitol Drugs Drug Resist. 2020 Dec;14:17-27. doi: 10.1016/j.ijpddr.2020.07.002. Epub 2020 Jul 22.
Malaria, leishmaniasis and trypanosomiasis are arthropod-borne, parasitic diseases that constitute a major global health problem. They are generally found in developing countries, where lack of access to preventive tools and treatment hinders their management. Because these parasites share an increased demand on glucose consumption with most cancer cells, six compounds used in anti-tumoral research were selected to be tested as antiparasitic agents in in vitro models of Leishmania infantum, Trypanosoma brucei, T. cruzi, and Plasmodium falciparum: dichloroacetic acid (DCA), 3-bromopyruvic acid (3BP), 2-deoxy-D-glucose (2DG), lonidamine (LND), metformin (MET), and sirolimus (SIR). No parasite-killing activity was found in L. infantum promastigotes, whereas DCA and 3BP reduced the burden of intra-macrophagic amastigotes. For T. brucei all selected compounds, but 2DG, decreased parasite survival. DCA, 2DG, LND and MET showed parasite-killing activity in T. cruzi. Finally, anti-plasmodial activity was found for DCA, 2DG, LND, MET and SIR. These results reinforce the hypothesis that drugs with proven efficacy in the treatment of cancer by interfering with ATP production, proliferation, and survival cell strategies might be useful in treating threatening parasitic diseases and provide new opportunities for their repurposing.
疟疾、利什曼病和锥虫病是节肢动物传播的寄生虫病，构成了一个主要的全球健康问题。它们通常在发展中国家发现，由于缺乏预防工具和治疗手段，阻碍了它们的管理。由于这些寄生虫与大多数癌细胞一样，对葡萄糖的消耗需求增加，因此选择了六种用于抗肿瘤研究的化合物，在体外模型中测试它们对利什曼原虫、布氏锥虫、克氏锥虫和恶性疟原虫的抗寄生虫作用：二氯乙酸（DCA）、3-溴丙酮酸（3BP）、2-脱氧-D-葡萄糖（2DG）、Lonidamine（LND）、二甲双胍（MET）和西罗莫司（SIR）。在利什曼原虫前鞭毛体中未发现寄生虫杀伤活性，而 DCA 和 3BP 减少了巨噬细胞内无鞭毛体的负担。对于 T. brucei，所有选定的化合物，除了 2DG，都降低了寄生虫的存活率。DCA、2DG、LND 和 MET 在 T. cruzi 中表现出寄生虫杀伤活性。最后，DCA、2DG、LND、MET 和 SIR 对疟原虫具有抗疟活性。这些结果强化了这样一种假设，即通过干扰 ATP 产生、增殖和存活细胞策略在癌症治疗中具有已证明疗效的药物，可能对治疗威胁性寄生虫病有用，并为它们的再利用提供了新的机会。
