• Home
  • Search Results
  • Inactivation of β-Lapachone Cytotoxicity by Filamentous Fungi that Mimic the Human Blood Metabolism.

Inactivation of β-Lapachone Cytotoxicity by Filamentous Fungi that Mimic the Human Blood Metabolism.

European journal of drug metabolism and pharmacokinetics (2016-04-10)
Camila Raquel Paludo, Eduardo Afonso da Silva-Junior, Eliane de Oliveira Silva, Ricardo Vessecchi, Norberto Peporine Lopes, Mônica Tallarico Pupo, Flavio da Silva Emery, Natália Dos Santos Gonçalves, Raquel Alves Dos Santos, Niege Araçari Jacometti Cardoso Furtado
ABSTRACT

β-Lapachone is a drug candidate in phase II clinical trials for treatment of solid tumors. The therapeutic efficacy of β-lapachone is closely related to its metabolism, since this o-naphthoquinone produces cytotoxic effect after intracellular bioreduction by reactive oxygen species formation. The aim of this study was to produce β-lapachone human blood phase I metabolites to evaluate their cytotoxic activities. The biotransformation of β-lapachone was performed using Mucor rouxii NRRL 1894 and Papulaspora immersa SS13. The metabolites were isolated and their chemical structures determined from spectrometric and spectroscopic data. Cell cytotoxicity assays were carried out with β-lapachone and its metabolites using the neoplastic cell line SKBR-3 derived from human breast cancer and normal human fibroblast cell line GM07492-A. Microbial transformation of β-lapachone by filamentous fungi resulted in the production of five metabolites identical to those found during human blood metabolism, a novel metabolite and a product stated before only in a synthetic procedure. The analysis of the results showed that β-lapachone metabolites were not cytotoxic for the neoplastic cell line SKBR-3 derived from human breast cancer and the normal human fibroblast cell line GM07492-A. The cytotoxic activity assay against the neoplastic cell line SKBR-3 revealed that the lowest half-maximal inhibitory concentration (IC The cytotoxic activity of β-lapachone in vivo may be reduced due to its swift conversion in blood.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Lapachol, 98%

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.