Synthesis and Antileishmanial Activity of 1,2,4,5-Tetraoxanes against Leishmania donovani

• Autor(a) principal: Cabral, Lília
• Data de Publicação: 2020
• Outros Autores: Pomel, Sébastien, Cojean, Sandrine, Amado, Patrícia, Loiseau, Philippe M., Cristiano, Maria De Lurdes
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.1/13609
• topic: Leishmaniasis; Antileishmanial chemotherapy; Peroxide-derived antimalarials; Antimalarials re-purposing; Tetraoxanes

A chemically diverse range of novel tetraoxanes was synthesized and evaluated in vitro against intramacrophage amastigote forms of Leishmania donovani. All 15 tested tetraoxanes displayed activity, with IC50 values ranging from 2 to 45 µm. The most active tetraoxane, compound LC140, exhibited an IC50 value of 2.52 ± 0.65 µm on L. donovani intramacrophage amastigotes, with a selectivity index of 13.5. This compound reduced the liver parasite burden of L. donovani-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.