<i>In vivo</i> gastroprotective effect of xyloccensin-E and xyloccensin-I from <i>Xylocarpus molluccensis</i> in rats

<div><p>Anti-ulcer activities of xyloccensin-E and xyloccensin-I were investigated in various ulcer models in Sprague-Dawley rats. The effects and the mechanism of action of both compounds for anti-secretory and cytoprotective activities were also studied. Both these active molecules improved the depleted levels of mucin and consequently inhibited the formation of erosions in a pyloric ligated ulcer model. Furthermore, xyloccensin-E and xyloccensin-I inhibited H⁺K⁺-ATPase activity <i>in vitro</i> confirming their anti-secretory activity. In conclusion, xyloccensin-E and xyloccensin-I were found to possess anti-ulcerogenic activity which might be due to their anti-secretory activity and subsequent strengthening of the defensive mechanism.</p></div

Identification of Novel Amino Acid Derived CCK-2R Antagonists As Potential Antiulcer Agent: Homology Modeling, Design, Synthesis, and Pharmacology

The present study revisited the three-dimensional (3D) homology model of CCK-2R using human A_2a adenosine receptor and the resolved NMR based structure of the third extracellular loop of the CCK-2R as templates. Further in order to identify novel antiulcer agents, rational designing have been performed utilizing the substructure of a well-known CCK-2R antagonist benzotript as a lead molecule and submitted to the combined docking and simulation studies. This led to the understanding of the essential structure requirement as well as variation of binding mode among conformational isomers of small molecule CCK-2R antagonists. In the next step, preparation of each configurational isomer of these molecules was carried out and submitted for their in vitro activity followed by in vivo screening into antiulcer rat model. The biological screening of these compounds has not only validated the developed homology model of CCK-2R but also led to the identification of highly potent CCK-2R antagonist <b>6a</b> as an orally active and safe candidate molecule having better antiulcer properties than the well-known drug benzotript