Evaluation of the intestinal absorption mechanism of casearin X in Caco-2 cells with Modified carboxylesterase activity

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Authors
Moreira da Silva, Rodrigo
De Gaitani, Cristiane Masetto
Moraes de Oliveira, Anderson Rodrigo
Pires Bueno, Paula Carolina
Cavalheiro, Alberto José
Peporine Lopes, Norberto
Butterweck, Veronika
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Publication date
2016
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01A - Journal article
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Journal of Natural Products
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Volume
79
Issue / Number
4
Pages / Duration
1084-1090
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American Chemical Society
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Abstract
The clerodane diterpene casearin X (1)​, isolated from the leaves of Casearia sylvestris, is a potential new drug candidate due to its potent in vitro cytotoxic activity. In this work, the intestinal absorption mechanism of 1 was evaluated using Caco-​2 cells with and without active carboxylesterases (CES)​. An LC-​MS method was developed and validated for the quantification of 1. The estn. of permeability coeffs. was possible only under CES-​inhibited conditions in which 1 is able to cross the Caco-​2 cell monolayer. The mechanism is probably by active transport, with no significant efflux, but with a high retention of the compd. inside the cells. The enzymic hydrolysis assay demonstrates the susceptibility of 1 to first-​pass metab. as substrate for specific CES expressed in human intestine.
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0163-3864
1520-6025
Language
English
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Yes
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Published
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Citation
MOREIRA DA SILVA, Rodrigo, Sheela VERJEE, Cristiane Masetto DE GAITANI, Anderson Rodrigo MORAES DE OLIVEIRA, Paula Carolina PIRES BUENO, Alberto José CAVALHEIRO, Norberto PEPORINE LOPES und Veronika BUTTERWECK, 2016. Evaluation of the intestinal absorption mechanism of casearin X in Caco-2 cells with Modified carboxylesterase activity. Journal of Natural Products. 2016. Bd. 79, Nr. 4, S. 1084–1090. DOI 10.1021/acs.jnatprod.5b01139. Verfügbar unter: http://hdl.handle.net/11654/23426