脱二氧喹烯酮的制备及其细胞毒性研究

Preparation and Cytotoxicity Investigation of Desoxyquinoceton

脱二氧喹烯酮为喹烯酮主要代谢物之一,了解脱二氧喹烯酮的安全性对喹烯酮的安全性评价具有重要意义。为评价脱二氧喹烯酮的药效及安全性,本研究探索体外合成制备脱二氧喹烯酮,并进行理化鉴定和抗菌活性测试;通过MTT方法研究脱二氧喹烯酮对Vero、HepG2、Chang Liver和L-02等多种细胞生长的抑制作用,利用单细胞电泳研究其对Chang Liver和L-02细胞DNA的损伤作用,利用流式细胞术研究其对Chang Liver和L-02细胞周期的改变。结果显示,体外成功合成制备出脱二氧喹烯酮,而脱二氧喹烯酮对各种细胞都具有较弱的生长抑制作用,其剂量检测范围内细胞抑制率均不到50%,但在较高剂量下脱二氧喹烯酮能导致细胞DNA损伤,主要表现为尾长和尾部DNA含量显著升高;并且脱二氧喹烯酮还改变Chang Liver细胞周期,表现为S期阻滞。说明脱二氧喹烯酮具有一定的细胞毒性。

Desoxyquinoceton is one of the major metabolites of quinocetone .For evaluation the safety and antibacterial effects of desoxyquinoceton ,we prepared desoxyquinoceton in vitro ,and identified the physi-cal and chemical characteristics ,and investigated its antibacterial activity ,studied the cell grow th inhibi-tion rates of Vero ,HepG2 ,Chang Liver and L-02 cell lines by MTT assay ,evaluated the DNA damages of Chang Liver and L-02 cells by single cell gel electrophoresis ,studied the changes of cell cycle with flow cy-tometry ,respectively .All results were carried on the statistics and analysis .The results showed that des-oxyquinoceton was successfully synthesized and has no antibacterial activity .The inhibition rates of des-oxyquinoceton within the detection dose range were less than 50% ,and it displayed the weak cell growth inhibitions effects on various cell lines .We found the DNA damage induced by desoxyquinoceton at higher doses ,expressed as tail length and tail DNA was significantly increased in Chang Liver and L-02 cells ;des-oxyquinoceton also changed the cell cycle on Chang liver cells with the S phase arrest .The results suggest desoxyquinoceton having certain degree cytotoxicity on various cell lines .