Center of Marine Sciences, CCMAR, Gambelas Campus, University of Algarve, UAlg, 8005-139 Faro, Portugal.
Department of Chemistry and Pharmacy, Faculty of Sciences and Technology, FCT, Gambelas Campus, University of Algarve, UAlg, Portugal.
Molecules. 2020 Jan 22;25(3):465. doi: 10.3390/molecules25030465.
A chemically diverse range of novel tetraoxanes was synthesized and evaluated in vitro against intramacrophage amastigote forms of . All 15 tested tetraoxanes displayed activity, with IC values ranging from 2 to 45 µm. The most active tetraoxane, compound LC140, exhibited an IC value of 2.52 ± 0.65 µm on intramacrophage amastigotes, with a selectivity index of 13.5. This compound reduced the liver parasite burden of -infected mice by 37% after an intraperitoneal treatment at 10 mg/kg/day for five consecutive days, whereas miltefosine, an antileishmanial drug in use, reduced it by 66%. These results provide a relevant basis for the development of further tetraoxanes as effective, safe, and cheap drugs against leishmaniasis.
合成了一系列具有化学多样性的新型四氧杂环己烷，并对其进行了体外抗巨噬细胞内利什曼原虫的活性评价。所有 15 种测试的四氧杂环己烷均具有活性，IC 值范围为 2 至 45 µm。最具活性的四氧杂环己烷化合物 LC140 对巨噬细胞内利什曼原虫的 IC 值为 2.52 ± 0.65 µm，选择性指数为 13.5。该化合物在腹腔内以 10 mg/kg/天连续 5 天给药后，可使感染的小鼠肝脏寄生虫负荷减少 37%，而米替福新（一种现有的抗利什曼病药物）可减少 66%。这些结果为进一步开发作为有效、安全和廉价的抗利什曼病药物的四氧杂环己烷提供了相关依据。
