Biotransformation of ²-lapachone using microbial cultures: an alternative to in vitro metabolism studies

• Grant number: 11/01303-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2011
• End date: January 31, 2013
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Niege Araçari Jacometti Cardoso Furtado
• Grantee: Camila Raquel Paludo
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 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, AP.BTA.TEM

Abstract

The goal of this project is to study the in vitro metabolism of ²-lapachone using microorganisms from gut and the fungus Mucor rouxii. This important naphthoquinone is acclaimed by its pharmacological activities, but there is no description in literature of ²-lapachone biotransformation studies. These studies can provide the obtention of new derivatives because microorganisms are capable of calalysing chemical reactions that will be not possible by using traditional chemical methods, with stereospecific reactions and the addition of non-reactive groups. Moreover, studies of drug biotransformations are an important and necessary step to evaluate the efficacy and security of drugs. ²-lapachone will be obtained by semi-synthesis from lapachol, which will be obtained from the inner bark and heartwood of Tabebuia avellanedae Lor. ex Griseb. The values of minimum inhibitory concentration of ²-lapachone will be determined against the microorganisms that will be used in the biotransformation studies to avoid toxic effects of this compound above the microorganisms. After biotransformation processes, extracts will be obtained from the culture broths and their chemical profiles will be evaluated. One or two promising processes will be selected for preparative scale development and the majority compounds will be isolated and their chemical structures will be elucidated. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PALUDO, CAMILA R.; DA SILVA-JUNIOR, EDUARDO A.; SANTOS, RAQUEL A.; PUPO, MONICA T.; EMERY, FLAVIO S.; FURTADO, NIEGE A. J. C.. Microbial transformation of beta-lapachone to its glycosides by Cunninghamella elegans ATCC 10028b. PHYTOCHEMISTRY LETTERS, v. 6, n. 4, p. 657-661, NOV 2013. (11/21700-5, 11/01303-1, 09/51812-0)

PALUDO, CAMILA RAQUEL; DA SILVA-JUNIOR, EDUARDO AFONSO; SILVA, ELIANE DE OLIVEIRA; VESSECCHI, RICARDO; LOPES, NORBERTO PEPORINE; PUPO, MONICA TALLARICO; EMERY, FLAVIO DA SILVA; GONCALVES, NATALIA DOS SANTOS; DOS SANTOS, RAQUEL ALVES; JACOMETTI CARDOSO FURTADO, NIEGE ARACARI. Inactivation of beta-Lapachone Cytotoxicity by Filamentous Fungi that Mimic the Human Blood Metabolism. EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, v. 42, n. 2, p. 213-220, APR 2017. (11/21700-5, 11/01303-1, 09/51812-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PALUDO, Camila Raquel. Biotransformation of B-lapachone using microbial cultures: an alternative to in vitro metabolism studies. 2013. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.