Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Departamento de Ciências Biológicas, Insituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
Parasite Immunol. 2020 Dec;42(12):e12784. doi: 10.1111/pim.12784. Epub 2020 Aug 30.
Treatment for visceral leishmaniasis (VL) is hampered by the toxicity and/or high cost of drugs, as well as by emergence of parasite resistance. Therefore, there is an urgent need for new antileishmanial agents.
In this study, the antileishmanial activity of a diprenylated flavonoid called 5,7,3,4'-tetrahydroxy-6,8-diprenylisoflavone (CMt) was tested against Leishmania infantum and L amazonensis species. Results showed that CMt presented selectivity index (SI) of 70.0 and 165.0 against L infantum and L amazonensis promastigotes, respectively, and of 181.9 and 397.8 against respective axenic amastigotes. Amphotericin B (AmpB) showed lower SI values of 9.1 and 11.1 against L infantum and L amazonensis promastigotes, respectively, and of 12.5 and 14.3 against amastigotes, respectively. CMt was effective in the treatment of infected macrophages and caused alterations in the parasite mitochondria. L infantum-infected mice treated with miltefosine, CMt alone or incorporated in polymeric micelles (CMt/Mic) presented significant reductions in the parasite load in distinct organs, when compared to the control groups. An antileishmanial Th1-type cellular and humoral immune response were developed one and 15 days after treatment, with CMt/Mic-treated mice presenting a better protective response.
Our data suggest that CMt/Mic could be evaluated as a chemotherapeutic agent against VL.
内脏利什曼病（VL）的治疗受到药物毒性和/或高成本以及寄生虫耐药性出现的阻碍。因此，迫切需要新的抗利什曼原虫药物。
在这项研究中，测试了一种被称为 5,7,3,4'-四羟基-6,8-二异戊烯基异黄酮（CMt）的双异戊烯基化黄酮对利什曼原虫和 L amazonensis 种的抗利什曼原虫活性。结果表明，CMt 对 L infantum 和 L amazonensis 前鞭毛体的选择性指数（SI）分别为 70.0 和 165.0，对相应的无环阿米巴体的 SI 分别为 181.9 和 397.8。两性霉素 B（AmpB）对 L infantum 和 L amazonensis 前鞭毛体的 SI 值分别为 9.1 和 11.1，对无环阿米巴体的 SI 值分别为 12.5 和 14.3。CMt 对感染的巨噬细胞有效，并导致寄生虫线粒体发生变化。与对照组相比，用米替福新、CMt 单独或掺入聚合物胶束（CMt/Mic）治疗的感染 L infantum 的小鼠在不同器官中的寄生虫负荷显著降低。在治疗后 1 天和 15 天，产生了抗利什曼原虫 Th1 型细胞和体液免疫反应，用 CMt/Mic 治疗的小鼠表现出更好的保护反应。
我们的数据表明，CMt/Mic 可作为治疗内脏利什曼病的化疗药物进行评估。
