Synthesis of a Novel Cyclic Prodrug of <i>S</i>‑Allyl-glutathione Able To Attenuate LPS-Induced ROS Production through the Inhibition of MAPK Pathways in U937 Cells

A novel cyclic prodrug of <i>S</i>-allyl-glutathione (<b>CP11</b>), obtained by using an acyloxy-alkoxy linker, was estimated for its pharmacokinetic and biological properties. The stability of <b>CP11</b> 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 <b>CP11</b> was assessed in U937 cells, an immortalized human monocyte cell line. Results showed that <b>CP11</b> 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 <b>CP11</b> is able to modulate inflammation mediated by LPS in U937 cells preventing the increase of ROS intracellular levels through interaction with the MAPK pathway