Leishmanicidal effect of LLD-3 (1), a nor-triterpene isolated from Lophanthera lactescens

Leishmanicidal activity of 6α, 7α, 15β, 16β, 24-pentacetoxy-22α-carbometoxy-21β,22β-epoxy-18β−hydroxy-27,30-bisnor-3,4-secofriedela-1,20 (29)-dien-3,4 R-olide (LLD-3 (1)) isolated from Lophanthera lactescens Ducke, a member of the Malpighiaceae, was demonstrated against intramacrophage amastigote forms (IC₅₀ of 0.41 μg/mL). The in vitro leishmanicidal effect of Glucantime, the first choice drug for leishmaniasis treatment, was increased by LLD-3 (1) association. The leishmanicidal effect of LLD-3 (1) was not due to stimulation of nitric oxide production by macrophages. LLD-3 (1) was also not cytotoxic for mouse peritoneal macrophages or B cells as assessed by the XTT and Trypan blue exclusion assays. LLD-3 (1) was unable to affect proliferation of naïve or activated B and T cells, as well as the B cells immunoglobulin synthesis. Cellularity of different tissues, liver and kidney functions were not altered in mice treated with LLD-3 (1), as well as the histology pattern of different organs. Our results add LLD-3 (1) as a potential drug candidate for treatment of leishmaniasis.