3-甲基喹噁啉-2-羧酸的制备及其细胞毒性

通过贝鲁特反应和还原、脱羧反应在体外合成制备3-甲基喹噁啉-2-羧酸,并进行理化鉴定和抗菌活性测试;通过MTT方法研究3-甲基喹噁啉-2-羧酸对多种细胞的生长抑制作用,利用单细胞电泳研究其对细胞DNA的损伤作用,利用流式细胞术研究其对细胞周期的改变。结果显示,体外成功合成制备出3-甲基喹噁啉-2-羧酸,而3-甲基喹噁啉-2-羧酸几乎没有抗菌效果,对多种细胞的生长抑制作用较弱,在剂量检测范围内细胞抑制率不到30%,但在一定剂量下能导致细胞DNA损伤,主要表现为尾长和尾部DNA含量显著升高;并且3-甲基喹噁啉-2-羧酸也能改变Chang细胞的细胞周期,表现为S期阻滞。结果表明,3-甲基喹噁啉-2-羧酸具有一定的细胞毒性。

Preparation and cytotoxicity of 3-methylquinoxaline-2-carboxylate

3-methylquinoxaline-2-carboxylate is one of the major metabolites quinocetone and olaquindox.For evaluation the safety of 3-methylquinoxaline-2-carboxylate,we prepared 3-methylquinoxaline-2-carboxylate by Beirut reaction,reduction reaction and decarboxylation in vitro,identified its physical and chemical characteristics,and investigated its antibacterial activity,studied the cell growth inhibition rates by MTT assay,evaluated the DNA damages by single cell gel electrophoresis,examined the changes of cell cycle with flow cytometry,respectively.The results showed that 3-methylquinoxaline-2-carboxylate was successfully synthesized and has not antibacterial activity.The inhibition rates of 3-methylquinoxaline-2-carboxylate within the detection dose range were less than 30%displayed the weak cells growth inhibitions effects on various cell lines.We found the DNA damage induced by 3-methylquinoxaline-2-carboxylate at higher doses,expressed as tail length and tail DNA was significantly increased;3-methylquinoxaline-2-carboxylate also changed the cell cycle on Chang liver cells with the S phase arrest.The results suggest 3-methylquinoxaline-2-carboxylate has a certain degree cytotoxicity on various cell lines.