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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: PHYTOCHEMISTRY LETTERS; v. 6, n. 4, p. 657-661, NOV 2013.
• Web of Science Citations: 6

Abstract

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)

• FAPESP's process: 11/21700-5 - The use of bacteria from gastrointestinal tract and filamentous fungi for biotransformation studies of naphthoquinones
• Grantee: Niege Araçari Jacometti Cardoso Furtado
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/01303-1 - Biotransformation of ²-lapachone using microbial cultures: an alternative to in vitro metabolism studies
• Grantee: Camila Raquel Paludo
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 09/51812-0 - Development of a platform for the study of in vitro and in vivo metabolism of natural products, a need for pre-clinical testing system
• Grantee: Norberto Peporine Lopes
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants