氟喹诺酮C-3芳苄叉基不饱和酮的合成及抗肿瘤活性研究  

Synthesis and Antitumor Activity of C-3 Arylidene-Substituted Fluoroquinolone Unsaturated Ketone Derivatives from Pefloxacin

作　　者：赵梦涛 曹智威 冯亚莉 胡国强 ZHAO Mengtao;CAO Zhiwei;FENG Yali;HU Guoqiang(Water Environment and Health Henan Engineering Technology Research Center,Zhengzhou University of Industrial Technology,Zhengzhou 451150,China;School of Clinical Medicine,Henan University,Kaifeng 475001,China)

机构地区：[1]郑州工业应用技术学院,河南省水环境与健康工程技术研究中心,河南郑州451150 [2]河南大学临床医学院,河南开封475001

出　　处：《生物化工》2022年第1期26-29,34,共5页Biological Chemical Engineering

基　　金：国家自然科学基金面上项目资助项目(20872028,21072045)。

摘　　要：为发现氟喹诺酮由抗菌活性向抗肿瘤活性转化的有效结构修饰策略,用芳苄叉基作为培氟沙星(1)C-3羧基的生物等排体,设计合成了9个新的氟喹诺酮不饱和酮目标化合物(3a~3i),其结构经元素分析和光谱数据确证,并评价了它们体外对SMMC-7721、Capan-1和HL60癌细胞株的抗增殖活性。结果表明,目标化合物的活性显著高于母体化合物1的抗肿瘤活性,其中氟苯基化合物3i的活性与对照抗肿瘤药阿霉素相当。因此,芳苄叉基替代C-3羧基构建的氟喹诺酮类化合物有利于提高其抗肿瘤活性,提示α,β-不饱和酮结构片段可能是C-3羧基的有效生物等排体。To further explore an effective structure modification strategy for the transformation of antibacterial fluoroquinolones into an antitumor ones,nine novel fluoroquinolone unsaturated ketone derivatives,1-ethyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-3-arylidene-2,3-dihydro-quinolin-4(1H)-ones(3a~3i),were constructed from pefloxacin(1)by an isosteric substitution of the C-3 carboxylic acid group with an arylidene group.The structures of the title compounds were characterized by elemental analysis and spectral data,and the results of the in vitro antitumor activity against SMMC-7721,Capan-1 and HL60 cell lines demonstrated more significantly antiproliferative activity than the parent 1.Meanwhile,the chlorophenyl compound(3i)showed a comparable activity to the comparasion doxorubicin.Thus,an arylidene group(α,β-unsaturated ketone structure)as a promising isostere of the C-3 carboxylic group for the improvement of the fluoroquinolone antitumor activity is well worth to be further developed.

关 键 词：氟喹诺酮 不饱和酮 等排体替代 抗肿瘤活性 

分 类 号：R914.5[医药卫生—药物化学]