Prediction Of Pharmacokinetic And Toxicological Parameters Of A 4-phenylcoumarin Isolated From Geopropolis: In Silico And In Vitro Approaches

dc.creatorda Cunha
dc.creatorMarcos Guilherme; Nobre Francob
dc.creatorGilson Cesar; Franchin
dc.creatorMarcelo; Beutler
dc.creatorJohn A.; de Alencar
dc.creatorSeverino Matias; Ikegaki
dc.creatorMasaharu; Rosalen
dc.creatorPedro Luiz
dc.date2016
dc.datenov
dc.date2017-11-13T13:57:24Z
dc.date2017-11-13T13:57:24Z
dc.date.accessioned2018-03-29T06:10:43Z
dc.date.available2018-03-29T06:10:43Z
dc.identifierToxicology Letters. Elsevier Ireland Ltd, v. 263, p. 6 - 10, 2016.
dc.identifier0378-4274
dc.identifier1879-3169
dc.identifierWOS:000390488200002
dc.identifier10.1016/j.toxlet.2016.10.010
dc.identifierhttp://www.sciencedirect.com/science/article/pii/S0378427416332842
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/330011
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1367036
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionIn 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.
dc.description263
dc.description6
dc.description10
dc.descriptionIntramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research
dc.descriptionFAPESP [2011/23635-6, 2012/22002-2]
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.languageEnglish
dc.publisherElsevier Ireland Ltd
dc.publisherClare
dc.relationToxicology Letters
dc.rightsfechado
dc.sourceWOS
dc.subjectIn Silico
dc.subjectIn Vitro
dc.subjectPharmacokinetics
dc.subjectGenotoxicity
dc.subjectCoumarin
dc.subjectGeopropolis
dc.titlePrediction Of Pharmacokinetic And Toxicological Parameters Of A 4-phenylcoumarin Isolated From Geopropolis: In Silico And In Vitro Approaches
dc.typeArtículos de revistas


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