Patruno Antonia, Fornasari Erika, Di Stefano Antonio, Cerasa Laura S, Marinelli Lisa, Baldassarre Leonardo, Sozio Piera, Turkez Hasan, Franceschelli Sara, Ferrone Alessio, Di Giacomo Viviana, Speranza Lorenza, Felaco Mario, Cacciatore Ivana
Department of Pharmacy and †Department of Medicine and Aging Science, University "G. D'Annunzio" , Via dei Vestini 31, 66100 Chieti, Italy.
Mol Pharm. 2015 Jan 5;12(1):66-74. doi: 10.1021/mp500431r. Epub 2014 Nov 19.
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 × 10(-6) cm s(-1), 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.
通过使用酰氧基 - 烷氧基连接体获得的一种新型S - 烯丙基 - 谷胱甘肽环前药（CP11），对其药代动力学和生物学特性进行了评估。在pH 1.2、7.4的不同酶浓度模拟液以及人血浆中评估了CP11的稳定性。在永生化人单核细胞系U937细胞中评估了CP11的抗炎能力。结果表明，CP11在酸性pH下稳定，由于在胃中停留时间较长，显示出口服给药的潜在优势。其渗透系数为2.49×10（-6）cm s（-1），被归类为具有离散血脑屏障渗透性的化合物。生物学研究表明，CP11能够调节U937细胞中由脂多糖介导的炎症，通过与丝裂原活化蛋白激酶（MAPK）途径相互作用防止细胞内活性氧（ROS）水平升高。
