Leishmaniasis is one of the most neglected parasitic infections of the world and current therapeutic options show several limitations. In the search for more effective drugs, plant compounds represent a powerful natural source. Artemisinin is a sesquiterpene lactone extracted from Artemisia annua L. leaves, from which dihydroartemisinin (DQHS) and artesunic acid (AA)/artesunate are examples of active derivatives. These lactones have been applied successfully on malaria therapy for decades. Herein, we investigated the sensitivity of Leishmania braziliensis, one of the most prevalent Leishmania species that cause cutaneous manifestations in the New World, to artemisinin, DQHS, and AA. L. braziliensis promastigotes and the stage that is targeted for therapy, intracelular amastigotes, were more sensitive to DQHS, showing EC₅₀ of 62.3 ± 1.8 and 8.9 ± 0.9 μM, respectively. Cytotoxicity assays showed that 50% of bone marrow-derived macrophages cultures were inhibited with 292.8 ± 3.8 μM of artemisinin, 236.2 ± 4.0 μM of DQHS, and 396.8 ± 6.7 μM of AA. The control of intracellular infection may not be essentially attributed to the production of nitric oxide. However, direct effects on mitochondrial bioenergetics and H₂O₂ production appear to be associated with the leishmanicidal effect of DQHS. Our data provide support for further studies of artemisinin and derivatives repositioning for experimental leishmaniasis.

利什曼病是世界上最被忽视的寄生虫感染之一，目前的治疗选择显示出一些局限性。在寻找更有效的药物的过程中，植物化合物代表了一种强大的天然来源。青蒿素是从青蒿叶中提取的倍半萜内酯，其中双氢青蒿素 (DQHS) 和青蒿酸 (AA)/青蒿琥酯是活性衍生物的例子。几十年来，这些内酯已成功应用于疟疾治疗。在此，我们调查了巴西利什曼原虫（在新大陆引起皮肤表现的最普遍的利什曼原虫之一）对青蒿素、DQHS 和 AA的敏感性。 巴西乳杆菌前鞭毛体和针对治疗的阶段，细胞内无鞭毛体，对 DQHS 更敏感，EC _{50 分别}为 62.3 ± 1.8 和 8.9 ± 0.9 μM。细胞毒性试验表明，50% 的骨髓衍生巨噬细胞培养物被 292.8 ± 3.8 μM 青蒿素、236.2 ± 4.0 μM DQHS 和 396.8 ± 6.7 μM AA 抑制。细胞内感染的控制可能并不主要归因于一氧化氮的产生。然而，对线粒体生物能学和 H ₂ O ₂产生的直接影响似乎与 DQHS 的利什曼原虫作用有关。我们的数据为进一步研究青蒿素及其衍生物在实验性利什曼病中的重新定位提供了支持。