Antifungal and Cytotoxic Assessment of Lapachol Derivatives Produced by Fungal Biotransformation

Autor(es)

Silva, Eliane O. ^[1] ; Ruano-Gonzalez, Antonio ^[2] ; dos Santos, Raquel A. ^[3] ; Sanchez-Maestre, Rosario ^[2] ; Furtado, Niege A. J. C. ^[1] ; Collado, Isidro G. ^[2] ; Aleu, Josefina ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Cadiz, Fac Ciencias, Campus Rio San Pedro, Puerto Real 11510, Cadiz - Spain

^[3] Univ Franca, Nucl Pesquisas Ciencias Exatas & Tecnol, BR-14404600 Franca, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NATURAL PRODUCT COMMUNICATIONS; v. 11, n. 1, p. 95-98, JAN 2016.
• Citações Web of Science: 1

Resumo

In the screening for biological active compounds, the biotransformation processes catalyzed by filamentous fungi are useful because they can provide information about the possible appearance of toxic metabolites after oral administration and also generate new leads. In this paper, biotransformation of lapachol (1) by three fungal strains, Mucor circinelloides NRRL3631, Botrytis cinerea UCA992 and Botrytis cinerea 2100, has been investigated for the first time. Lapachol (1) was biotransformed into avicequinone-A (2) by M circinelloides, 3'-hydroxylapachol (3) by B. cinerea, and into dehydro-a-lapachone (4) by both fungi. All these compounds were evaluated for their cytotoxic activities. The metabolite 2 displayed non-selective cytotoxicity against tumor and normal cell lines, 3 did not show cytotoxicity against the same cells, while 4 showed higher cytotoxicity against cancer cell lines than lapachol (1). The transformation of 1 into harmless and reactive metabolites evidences the importance of the evaluation of drug metabolism in the drug discovery process. Antifungal potential of lapachol (1) and its metabolites 2 and 4 against B. cinerea has also been evaluated. Dehydro-a-lapachone (4) has been shown to be less toxic to fungal growth than lapachol (1), which indicates a detoxification mechanism of the phytopathogen. (AU)

• Processo FAPESP: 11/21700-5 - Utilização de bactérias do trato gastrointestinal e fungos filamentosos para estudos de biotransformação de naftoquinonas
• Beneficiário: Niege Araçari Jacometti Cardoso Furtado
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/51812-0 - Desenvolvimento de uma plataforma para o estudo do metabolismo in vivo e in vitro de produtos naturais, uma necessidade para o sistema de ensaios pré-clínicos
• Beneficiário: Norberto Peporine Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático