Evaluation of the Intestinal Absorption Mechanism of Casearin X in Caco-2 Cells with Modified Carboxylesterase Activity

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• 作者：Rodrigo Moreira da Silva ; Sheela Verjee ; Cristiane Masetto de Gaitani ; Anderson Rodrigo Moraes de Oliveira ; Paula Carolina Pires Bueno ; Alberto José Cavalheiro ; Norberto Peporine Lopes ; Veronika Butterweck
• 刊名：Journal of Natural Products
• 出版年：2016
• 出版时间：April 22, 2016
• 年：2016
• 卷：79
• 期：4
• 页码：1084-1090
• 全文大小：395K
• 年卷期：0
• ISSN：1520-6025

文摘

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.