Identification of quinoline-chalcone hybrids as potential antiulcer agents

• A series of quinoline-chalcone hybrids were designed and synthesized.
• Hybrids were evaluated in various ulcer models in Sprague–Dawley (SD) rats.
• The hybrids 14, 16, 17, 23, 29, 31, 32 and 35 showed significant gastroprotection.
• The cytoprotective effect of lead hybrid 17 was established.

Antiulcer activity of novel quinoline-chalcone hybrids (13–37) was investigated. Among them, eight compounds (14, 16, 17, 23, 29, 31, 32 and 35) were found to be active in various ulcer models in Sprague–Dawley (SD) rats. To understand the mechanism of action of these hybrids, the effects of the compounds on antisecretory and cytoprotective activities were studied. All these active hybrids improved the depleted levels of mucin and consequently inhibited the formation of erosions in a pyloric ligated ulcer model. In addition, they also significantly increased the gastric PGE2 content in an aspirin induced ulcer model. The additional experiments including the in vitro metabolic stability and in vivo pharmacokinetics led to the identification of compound 17 as an orally active and safe candidate that is worthy of further investigation to be developed as an antiulcer agent.

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