Evaluation of the Intestinal Absorption Mechanism of Casearin X in Caco-2 Cells with Modified Carboxylesterase Activity
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Amer Chemical Soc
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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 estimation of permeability coefficients 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 compound inside the cells. The enzymatic hydrolysis assay demonstrates the susceptibility of 1 to first-pass metabolism as substrate for specific CES expressed in human intestine.
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Journal Of Natural Products. Washington: Amer Chemical Soc, v. 79, n. 4, p. 1084-1090, 2016.
