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Da Costa, J. C. Alcaloidic heterosides from Solanum lycocarpum A. St.-Hil.: evaluation of the activities against dermatophytic fungus and skin cancer. 2012. 69 p. Dissertation (Master). Faculdade de Ciências Farmacêuticas de Ribeirão Preto – Universidade de São Paulo, Ribeirão Preto, 2012. Solanum lycocarpum A. Saint-Hilaire (Solanaceae), commonly known as wolf apple or wolf ́s fruit, is a plant native of Brazil very common in the Brazilian savanna. High concentrations of steroidal alkaloids are found in S. lycocarpum fruits, and solasonine (SS) and solamargine (SM) are the most important ones. These two alkaloids present potential antifungal and anticancer activities. Dermatophytic fungi are the most common agents responsible for superficial mycoses in humans and animals, by infecting exclusively the stratum corneum of skin, hair and nails. Skin cancer is the most frequent type corresponding to roughly 25% of all the malignant tumors registered in Brazil. A topical formulation for skin cancer treatment was developed by our research group and its stability tests are reported in this work. The S. lycocarpum fruits were collected, dried, milled and submitted to acid-base extraction furnishing a precipitate, which was solubilized in ethanol and then filtered. The heterosidic alkaloids SS and SM were isolated by using vacuum column chromatography and purified by semi-preparative HPLC. The formulation containing the alkaloidic extract stored at room temperature (27 ± 2 C) was more stable than the ones in other conditions. Antifungal in vitro test of the alkaloidic extract, SS, SM and the aglycone (SD) were performed with Candida spp and dermatophytic fungi strains. The alkaloid SM displayed the lower inhibitory concentration. The toxicity of the alkaloidic extract, SS, SM and SD was verified in a cytotoxicicity test performed with both cultured human cells of spinocellular carcinoma (A431) and mice fibroblast cells (L929). An in vivo cytotoxicicity test was performed by inducing non-melanoma skin cancer in mice with spinocellular cells A431, in which only the animals treated with a commercial formulation Curaderm BEC 5, showed tumor reduction. There was no statistical difference between the group treated with the formulation containing the alkaloidic extract and control groups. Histological analysis confirmed that the skin cancer induced in the animals were spinocellular type. In an immunohistoquimic test, caspase-3 antibody was employed to stain the cells in apoptosis in the tumors, showing that apoptotic cells were more numerous in the group treated with the formulation Curaderm BEC 5.

Heterosídeos alcaloídicos de Solanum lycocarpum A. St.-Hil.: avaliação das atividades contra fungos dermatófitos e câncer de pele