郑州大学学报(医学版)
鄭州大學學報(醫學版)
정주대학학보(의학판)
JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES)
2015年
5期
597-601
,共5页
尚慧杰%高留州%谢玉锁%闫强%吴书敏%倪礼礼%黄文龙%谢松强%胡国强
尚慧傑%高留州%謝玉鎖%閆彊%吳書敏%倪禮禮%黃文龍%謝鬆彊%鬍國彊
상혜걸%고류주%사옥쇄%염강%오서민%예례례%황문룡%사송강%호국강
氟喹诺酮%酰腙%生物电子等排体%抗肿瘤活性
氟喹諾酮%酰腙%生物電子等排體%抗腫瘤活性
불규낙동%선종%생물전자등배체%항종류활성
fluoroquinolone%acylhydrazone%bioisostere%antitumor activity
目的:寻找转化抗菌氟喹诺酮到抗肿瘤氟喹诺酮的有效策略。方法:用酰腙作为N-甲基环丙沙星C-3羧基的生物电子等排体,合成了12个环丙沙星酰腙目标化合物,其结构经元素分析和光谱数据确证。用MTT方法评价了目标化合物体外对SMMC-7721、L1210和HL603种癌细胞的生长抑制活性。结果:酰腙目标物对3种实验癌细胞的生长抑制活性显著强于母体环丙沙星。构-效关系表明,苯环带吸电子化合物的活性强于供电子化合物的活性,尤其带羧基和磺酰胺基化合物的活性强于其他取代基化合物的活性。结论:氟喹诺酮C-3羧基并非是抗肿瘤活性所必需的药效团,被酰腙取代可提高其抗肿瘤活性。
目的:尋找轉化抗菌氟喹諾酮到抗腫瘤氟喹諾酮的有效策略。方法:用酰腙作為N-甲基環丙沙星C-3羧基的生物電子等排體,閤成瞭12箇環丙沙星酰腙目標化閤物,其結構經元素分析和光譜數據確證。用MTT方法評價瞭目標化閤物體外對SMMC-7721、L1210和HL603種癌細胞的生長抑製活性。結果:酰腙目標物對3種實驗癌細胞的生長抑製活性顯著彊于母體環丙沙星。構-效關繫錶明,苯環帶吸電子化閤物的活性彊于供電子化閤物的活性,尤其帶羧基和磺酰胺基化閤物的活性彊于其他取代基化閤物的活性。結論:氟喹諾酮C-3羧基併非是抗腫瘤活性所必需的藥效糰,被酰腙取代可提高其抗腫瘤活性。
목적:심조전화항균불규낙동도항종류불규낙동적유효책략。방법:용선종작위N-갑기배병사성C-3최기적생물전자등배체,합성료12개배병사성선종목표화합물,기결구경원소분석화광보수거학증。용MTT방법평개료목표화합물체외대SMMC-7721、L1210화HL603충암세포적생장억제활성。결과:선종목표물대3충실험암세포적생장억제활성현저강우모체배병사성。구-효관계표명,분배대흡전자화합물적활성강우공전자화합물적활성,우기대최기화광선알기화합물적활성강우기타취대기화합물적활성。결론:불규낙동C-3최기병비시항종류활성소필수적약효단,피선종취대가제고기항종류활성。
Aim:To explore an efficient strategy for a transformation of antibacterial fluoroquinolone into antitumor flu -oroquinolones .Methods:An acylhydrazone used as bioisostere of the C-3 carboxylic group ,twelve novel fluoroquinolone C-3 acylhydrazones were synthesized from ciprofloxacin ,respectively .The structures of the title compounds were characterized by elemental analysis and spectral data , and the in vitro antitumor activity against SMMC-7721 , L1210 and HL60 cells were also evaluated by MTT assay .Results: The title compounds exhibited more significantly inhibitory activity than the parent.The SAR showed that some title compounds with electron-withdrawing groups had more potent cytotoxicity than that of compounds with electron-donating group .In particular , some compounds bearing carboxylic group and sulfonamide group had better activity than other title compounds .Conclusion:It appears to be not necessary for the C-3 carboxylic group to develop antitumor fluoroquinolones ,and the bioisosteric replacement with a acylhydrazone group could improve the antitumor activity.