The rational search of novel bioactive molecules against pathogens with immunomodulatory activity is presently one of the most significant approaches to discover and design new therapeutic agents for effective control of infectious diseases, such as the infection caused by Leishmania parasites. In the present study, we evaluated the therapeutic efficacy of the recently characterized immunomodulatory compound 11α,19β-dihydroxy-7-acetoxy-7-deoxoichangin, a seco-limonoid derived from the bark of Raputia heptaphylla (Pittier) using: (1) peritoneal macrophages and (2) Mesocricetus auratus hamsters infected with Leishmania (V.) panamensis and Leishmania (L.) amazonensis. We observed the ability of this seco-limonoid to induce the effective control of the parasite either in vitro [determining an effective concentration 50 (EC50) of 59 µ m at the infection model] and in vivo (inducing clinical improvement or even cure in infected animals treated compared with the groups of animals treated with vehicle solution or meglumine antimoniate).

The high morbidity generated by the infection caused by parasites of the genus Leishmania, make of this infection into one of the vector-borne infectious diseases most relevant worldwide, which added to the fact that the drugs used for its treatment are far from be optimal and considering that prophylactic approaches (such as the development of a vaccine) still seems far from being achieved, make of the search for new therapeutic alternatives for safe and effective treatment of this disease one of the most accurate approaches to the control of this disease. In this study we evaluated the antileishmanial and immunomodulatory activity of the compound 11α,19β-dihydroxy-7-acetoxy-7-deoxoichangin (a seco-limonid molecule) through: 1) evaluation of its cytotoxicity over promastigotes and axenic amastigotes of L. (V) panamensis, 2) determination of its ability to induce the control of in vitro infection, using infected murine cells (J774.2) and human dendritic cells (hDCs), 3) quantifying the levels of pro-inflammatory cytokines, (iv) evaluating the expression of cell markers associated with hDCs maturation, and (v) determinating the production of nitric oxide free radicals (NO). In this regard, this seco-limonoid exhibited an antileishmanial activity represented in the reduction of in vitro infection in J774.2 cells and hDCs, with a EC 50 of 7.9 µM (4.48 µg/mL) and 25.5 µM (14.39 µg/mL), respectively, and additionally, we observed an increase on the production of IL-12p70, TNF-α and NO, as also, in the number of hDCs HLA-DR-positive in treated infected hDCs. These findings suggest that anti-leishmanial activity of this compound could be associated with the potential "reactivation" of phagocytic cell that is "paralyzed" by the infection, generating an immune phenotype associated with protection.

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Del extracto etanólico de la parte aérea de Solanum cornifolium fueron aislados â-sitosterol, estigmasterol, lupeol y un nuevo alcaloide esteroidal 23,24-(-2-metil-tetrahidrofurano)-solanidina. Sus estructuras fueron elucidadas por RMN, incluyendo técnicas 2D y por comparación con datos de la literatura.