N-(5-芳苄叉基饶丹宁)环丙沙星酰胺的合成及抗肿瘤活性  

Synthesis and Antitumor Activity of N-Arylidene-Rhodanine Ciprofloxacin Amides

作　　者：张会丽 姜亚玲 胡国强[2] 黄文龙[3] ZHANG Hui-li;JIANG Ya-ling;HU Guo-qiang;HUANG Wen-long(Institute of Pharmaceutical Applied Technology,Zhengzhou University of Industrial Technology,Zhengzhou 451100,China;School of Pharmacy,Henan University,Kaifeng 475001,China;Center of Drug Discovery,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]郑州工业应用技术学院药学应用技术研究所,河南郑州451100 [2]河南大学药学院,河南开封475001 [3]中国药科大学新药研究中心,江苏南京210009

出　　处：《化学试剂》2019年第12期1334-1338,共5页Chemical Reagents

基　　金：国家自然科学基金面上资助项目(20872028,21072045);河南省科技发展计划资助项目(162102310392);学校科研资助项目(2018YB023)

摘　　要：探索抗菌氟喹诺酮向抗肿瘤活性转化的结构修饰策略。用酰氨基为环丙沙星C-3羧基的电子等排体,5-芳苄叉基饶丹宁为其功能修饰基,合成了11个新的目标化合物,其结构经元素分析和光谱数据确证,评价其体外对SMMC-7721、Panc-1和HL60癌细胞株及VERO正常细胞株生长抑制活性。目标化合物抗肿瘤活性显著强于母体环丙沙星,且对VERO细胞表现出较低的细胞毒性作用,尤其是卤代苯基或硝基苯基或芳香杂环类化合物的IC50已达到微摩尔浓度,与对照阿霉素相当。芳苄叉基饶丹宁修饰的酰氨基替代C-3羧基有利于提高氟喹诺酮的抗肿瘤活性。To explore an efficiently structural modifition strategy for a transformation of antibacterial fluoroquinolones into an antitumor fluoroquinolones.Eleven novel title compounds were synthesized with an amide group as the bioisostere of the C-3 carboxylic group modified by a functionalized arylidene rhodanine scaffold from ciprofloxacin,respectively.The structures were confirmed by spectral data and elemental analysis,and the in vitro anti-cell proliferation activity against SMMC-7721,Panc-1,HL60 and VERO cells were evaluated.The title compounds showed more significant potency than ciprofloxacin along with lower cytotoxicity against the normal VERO cells than comparison doxorubicin,respectively.In particular,compounds bearing a halogen or nitro-phenyl or heteroaromatic ring showed comparable activity to comparison doxorubicin.An amide group modified by arylidene rhodanine scaffold as a bioisostere of the C-3 carboxylic acid group appears to an alternative route for the improvement of the antitumor activity.

关 键 词：氟喹诺酮 环丙沙星酰胺 饶丹宁 Α Β-不饱和酮 电子等排体 抗肿瘤活性 

分 类 号：O629.3[理学—有机化学]