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

Abstract

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.

• Authors: Lília I L Cabral, Sébastien Pomel, Sandrine Cojean, Patrícia S M Amado, Philippe M Loiseau, Maria L S Cristiano
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 25 Issue 3 (Jan 22 2020) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 31979089 (Publication Type: Letter)

Chemical References

• Antiprotozoal Agents
• Tetraoxanes
• Phosphorylcholine
• miltefosine

Topics

• Animals
• Antiprotozoal Agents (chemistry, therapeutic use)
• Leishmania donovani (drug effects, pathogenicity)
• Leishmaniasis (drug therapy, parasitology)
• Mice
• Phosphorylcholine (analogs & derivatives, chemistry, therapeutic use)
• Tetraoxanes (chemistry, therapeutic use)