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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Prediction of pharmacokinetic and toxicological parameters of a 4-phenylcoumarin isolated from geopropolis: In silico and in vitro approaches

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Autor(es):
da Cunha, Marcos Guilherme ; Nobre Francob, Gilson Cesar ; Franchin, Marcelo ; Beutler, John A. ; de Alencar, Severino Matias ; Ikegaki, Masaharu ; Rosalen, Pedro Luiz
Número total de Autores: 7
Tipo de documento: Artigo Científico
Fonte: Toxicology Letters; v. 263, p. 6-10, NOV 30 2016.
Citações Web of Science: 1
Resumo

In silico and in vitro methodologies have been used as important tools in the drug discovery process, including from natural sources. The aim of this study was to predict pharmacokinetic and toxicity (ADME/Tox) properties of a coumarin isolated from geopropolis using in silico and in vitro approaches. Cinnamoyloxy-mammeisin (CNM) isolated from Brazilian M. scutellaris geopropolis was evaluated for its pharmacokinetic parameters by in silico models (ACD/Percepta (TM) and MetaDrug (TM) software). Genotoxicity was assessed by in vitro DNA damage signaling PCR array. CNM did not pass all parameters of Lipinski's rule of five, with a predicted low oral bioavailability and high plasma protein binding, but with good predicted blood brain barrier penetration. CNM was predicted to show low affinity to cytochrome P450 family members. Furthermore, the predicted Ames test indicated potential mutagenicity of CNM. Also, the probability of toxicity for organs and tissues was classified as moderate and high for liver and kidney, and moderate and low for skin and eye irritation, respectively. The PCR array analysis showed that CNM significantly upregulated about 7% of all DNA damage-related genes. By exploring the biological function of these genes, it was found that the predicted CNM genotoxicity is likely to be mediated by apoptosis. The predicted ADME/Tox profile suggests that external use of CNM may be preferable to systemic exposure, while its genotoxicity was characterized by the upregulation of apoptosis-related genes after treatment. The combined use of in silico and in vitro approaches to evaluate these parameters generated useful hypotheses to guide further preclinical studies. (C) 2016 Elsevier Ireland Ltd. All rights reserved. (AU)

Processo FAPESP: 12/22002-2 - Identificação química de biocompostos e alvos moleculares da geoprópolis sobre células cancerosas
Beneficiário:Marcos Guilherme da Cunha
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
Processo FAPESP: 11/23635-6 - Avaliação farmacológica e isolamento de moléculas bioativas da fração hexânica da geoprópolis de melipona scutellaris
Beneficiário:Marcos Guilherme da Cunha
Modalidade de apoio: Bolsas no Brasil - Doutorado