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Master's Dissertation
DOI
https://doi.org/10.11606/D.60.2012.tde-05072012-104926
Document
Author
Full name
Juliana de Carvalho da Costa
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2012
Supervisor
Committee
Bastos, Jairo Kenupp (President)
Furtado, Niege Araçari Jacometti Cardoso
Tavares, Denise Crispim
Title in Portuguese
Heterosídeos alcaloídicos de Solanum lycocarpum A. St.-Hil.: avaliação das atividades contra fungos dermatófitos e câncer de pele
Keywords in Portuguese
dermatófitos
formulação tópica e anticâncer
solamargina
Solanum lycocarpum
solasonina
Abstract in Portuguese
de pele é o tipo mais frequente, correspondendo a cerca de 25% de todos os tumores malignos registrados no Brasil. Há que se destacar que uma formulação de uso tópico foi desenvolvida pelo grupo para uso contra câncer de pele e o estudo da estabilidade acelerada desta formulação foi avaliado nesse trabalho. Os frutos da espécie S. lycocarpum foram coletados, secos, triturados, submetidos à extração ácido-base e o precipitado foi suspenso em etanol e filtrado. Os heterosídeos alcaloídicos, SS e SM, foram isolados por cromatografia em coluna a vácuo e purificados em CLAE semipreparativa. A formulação contendo extrato alcaloídico armazenada em temperatura ambiente (27 ± 2 oC) apresentou a melhor estabilidade física. Ensaios para avaliação da atividade antifúngica in vitro do extrato alcaloídico, SS, SM e aglicona (SD) foram realizados com cepas de fungos dermatófitos e Candida spp., sendo que a SM apresentou o menor valor de concentração inibitória. No ensaio de citotoxidade em células humanas de carcinoma espinocelular (A431) e células de fibroblastos de camundongos (L929) foi possível observar a toxidade do extrato alcaloídico e das substâncias, SS, SM e SD frente às células cancerígenas. No ensaio in vivo, os animais foram induzidos ao câncer de pele não-melanoma do tipo espinocelular com células A431 e verificou-se que apenas o grupo de animais tratados com a formulação Curaderm BEC 5 apresentou redução tumoral. Em contrapartida, o grupo tratado com formulação contendo extrato alcaloídico se comportou da mesma maneira que os grupos controle da formulação e controle negativo. Com auxílio da histologia confirmou-se que o câncer de pele induzido nos animais foi do tipo espinocelular. No ensaio imunoistoquímico foi utilizado o anticorpo caspase-3 para marcar as células em apoptose nos tumores, sendo que o maior número de células apoptóticas foi verificada no grupo tratado com a formulação Curaderm BEC 5.
Title in English
Alcaloidic heterosides from Solanum lycocarpum A. St.-Hil.: evaluation of the activities against dermatophytic fungus and skin cancer
Keywords in English
anticancer topical formulation
dermatophytes
solamargin
Solanum lycocarpum
solasonin
Abstract in English
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 oC) 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.
 
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2013-05-03
 
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