Synthesis of a Novel Cyclic Prodrug of S-Allyl-glutathione Able To Attenuate LPS-Induced ROS Production through the Inhibition of MAPK Pathways in U937 Cells
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- 作者：Antonia Patruno ; Erika Fornasari ; Antonio Di Stefano ; Laura S. Cerasa ; Lisa Marinelli ; Leonardo Baldassarre ; Piera Sozio ; Hasan Turkez ; Sara Franceschelli ; Alessio Ferrone ; Viviana Di Giacomo ; Lorenza Speranza ; Mario Felaco ; Ivana Cacciatore
- 刊名：Molecular Pharmaceutics
- 出版年：2015
- 出版时间：January 5, 2015
- 年：2015
- 卷：12
- 期：1
- 页码：66-74
- 全文大小：497K
- ISSN：1543-8392
文摘
A novel cyclic prodrug of S-allyl-glutathione (CP11), obtained by using an acyloxy-alkoxy linker, was estimated for its pharmacokinetic and biological properties. The stability of CP11 was evaluated at pH 1.2, 7.4, in simulated fluids with different concentrations of enzymes, and in human plasma. The anti-inflammatory ability of CP11 was assessed in U937 cells, an immortalized human monocyte cell line. Results showed that CP11 is stable at acidic pH showing a possible advantage for oral delivery due to the longer permanence in the stomach. Having a permeability coefficient of 2.49 脳 10鈥? cm s鈥?, it was classified as discrete BBB-permeable compound. Biological studies revealed that CP11 is able to modulate inflammation mediated by LPS in U937 cells preventing the increase of ROS intracellular levels through interaction with the MAPK pathway.