药学学报, 2014, 49(12): 1694-1698
引用本文:
高留州, 谢玉锁, 李涛, 黄文龙, 胡国强. C-3噁二唑硫乙酰腙取代的氟喹诺酮类似物的合成、抗肿瘤活性及构-效关系[J]. 药学学报, 2014, 49(12): 1694-1698.
GAO Liu-zhou, XIE Yu-suo, LI Tao, HUANG Wen-long, HU Guo-qiang. Synthesis, antitumor activity and SAR of C-3 oxadiazole sulfanylacetylhydrazone-substituted fluoroquinolone analogues[J]. Acta Pharmaceutica Sinica, 2014, 49(12): 1694-1698.

C-3噁二唑硫乙酰腙取代的氟喹诺酮类似物的合成、抗肿瘤活性及构-效关系
高留州1, 谢玉锁1, 李涛1, 黄文龙2, 胡国强1
1. 河南大学化学生物学研究所, 河南 开封 475001;
2. 中国药科大学新药研究中心, 江苏 南京 210009
摘要:
为寻找氟喹诺酮由抗菌活性转化为抗肿瘤活性的有效策略, 基于药效团拼合原理, 用噁二唑替代培氟沙星C-3位羧基, 功能酰腙基为其修饰基团, 设计合成了C-3噁二唑硫乙酰腙目标化合物7a7o, 目标化合物结构经元素分析、1H NMR、MS确证.采用MTT法评价了目标化合物对人肝癌Hep-3B细胞株的体外增殖抑制活性.结果表明, 15个目标化合物活性均显著高于对照培氟沙星的活性, 其中带吸电子取代基化合物的活性高于供电子基团化合物的活性, 尤其是含羧基取代基化合物的活性与对照抗肿瘤药物阿霉素相当, 表明芳环羧基修饰基的存在有利于提高抗肿瘤活性.
关键词:    氟喹诺酮      噁二唑      酰腙      抗肿瘤活性      构-效关系     
Synthesis, antitumor activity and SAR of C-3 oxadiazole sulfanylacetylhydrazone-substituted fluoroquinolone analogues
GAO Liu-zhou1, XIE Yu-suo1, LI Tao1, HUANG Wen-long2, HU Guo-qiang1
1. Institute of Chemistry and Biology, Henan University, Kaifeng 475001, China;
2. Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China
Abstract:
To explore an efficient strategy for the conversion of antibacterial fluoroquinolones into antitumor fluoroquinolones, an azole heterocyclic ring of oxadiazole instead of the C-3 carboxylic acid group with a functionalized hydrazone group as a modified side-chain, fifteen novel 2-(fluoroquinolon-3-yl)-oxadiazole-5-sulfanylacetylhydrazone derivatives 7a-7o were designed and synthesized on the basis of the pharmacophore hybridization principle from pefloxacin, separately. The structures for fifteen title compounds were characterized by elemental analysis, 1H NMR and MS, and their in vitro antitumor activity against Hep-3B cell line was evaluated by a MTT assay. The results showed that the title compounds exhibited more significantly inhibitory activity than that of the parent pefloxacin, in which compounds with electron-withdrawing group attached on aryl ring had more potency than that of compounds with electron donating group, especially compounds with a carboxylic substituent were comparable to comparison doxorubicin. It suggests that it is favorable for an improvement of antitumor activity to remain a carboxylic acid unit at the aromatic ring.
Key words:    fluoroquinolone    oxadiazole    acylhydrazone    antitumor activity    SAR   
收稿日期: 2014-07-12
基金项目: 国家自然科学基金资助项目(20872028,21072045);河南大学科研基金资助.
通讯作者: 胡国强
Email: hgqxy@sina.com.cn
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