Sashidhara Koneni V, Avula Srinivasa Rao, Mishra Vaibhav, Palnati Gopal Reddy, Singh L Ravithej, Singh Neetu, Chhonker Yashpal S, Swami Priyanka, Bhatta R S, Palit Gautam
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
Eur J Med Chem. 2015 Jan 7;89:638-53. doi: 10.1016/j.ejmech.2014.10.068. Epub 2014 Oct 24.
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.
研究了新型喹啉-查尔酮杂合物（13 - 37）的抗溃疡活性。其中，发现有八种化合物（14、16、17、23、29、31、32和35）在斯普拉格-道利（SD）大鼠的各种溃疡模型中具有活性。为了解这些杂合物的作用机制，研究了这些化合物对抑酸和细胞保护活性的影响。所有这些活性杂合物均提高了粘蛋白耗竭水平，从而在幽门结扎溃疡模型中抑制了糜烂的形成。此外，它们在阿司匹林诱导的溃疡模型中还显著增加了胃前列腺素E2含量。包括体外代谢稳定性和体内药代动力学在内的进一步实验，确定化合物17为口服活性且安全的候选物，值得作为抗溃疡药物进行进一步研究开发。
