Microbial transformation of beta-lapachone to its glycosides by Cunninghamella elegans ATCC 10028b

Autor(es)

Paludo, Camila R. ^[1] ; da Silva-Junior, Eduardo A. ^[1] ; Santos, Raquel A. ^[2] ; Pupo, Monica T. ^[1] ; Emery, Flavio S. ^[1] ; Furtado, Niege A. J. C. ^[1]

Afiliação do(s) autor(es)

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

^[2] Univ Franca, Nucleo Pesquisas Ciencias Exatas & Tecnol, BR-14404600 Franca, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PHYTOCHEMISTRY LETTERS; v. 6, n. 4, p. 657-661, NOV 2013.
• Citações Web of Science: 6

Resumo

beta-lapachone (1) has entered phases I and II clinical trials for the treatment of solid tumors and the therapeutic efficacy of beta-lapachone is closely related to its metabolic process. In order to contribute to a better understanding of human metabolism of beta-lapachone, Cunninghamella elegans ATCC 10028b was used as a microbial model of mammalian metabolism to biotransform beta-lapachone and two new glycosylated derivatives were produced. The chemical structures were elucidated as 6-hydroxy-2,2-dimethyl-3,4-dihydro-2H-naphtho{[}1,2-b]pyran-5-O-beta-D-g lucopyranoside (2) and 5-hydroxy-2,2-dimethyl-3,4-dihydro-2H-naphtho{[}1,2-b]pyran-6-O-beta-D-g lucopyranoside (3) by H-1 NMR, C-13 NMR, HMBC, HMQC, COSY and HRMS analyses. The major derivative (3) displayed a lower activity against breast cancer cell line SKBR-3 (IC50 = 312.5 mu M) than beta-lapachone (IC50 = 5.6 mu M), but did not show cytotoxicity against normal fibroblasts cell line GM07492-A, whereas beta-lapachone was highly toxic (IC50 = 7.25 mu M). These metabolites were reported here for the first time and are similar to those that occur in phase II of human metabolism (C) 2013 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved. (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: 11/01303-1 - Biotransformação da ²-lapachona utilizando culturas microbianas: uma alternativa para estudos de metabolismo in vitro
• Beneficiário: Camila Raquel Paludo
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• 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