7-((4-Substituted)piperazin-1-yl) derivatives of ciprofloxacin: Synthesis and in vitro biological evaluation as potential antitumor agents
7-((4-Substituted)piperazin-1-yl) derivatives of ciprofloxacin: Synthesis and in vitro biological evaluation as potential antitumor agents
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DOI：
10.1016/j.bmc.2009.06.053
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发表时间：
2009-08-01
影响因子：
3.5
通讯作者：
Kiss, Robert
中科院分区：
文献类型：
--
作者：
Azema, Joelle;Guidetti, Brigitte;Kiss, Robert
环丙沙星（CP），一种抗生素已被证明在几种癌细胞系中具有抗增殖和凋亡活性。此外，一些报道强调了增加亲脂性以提高抗肿瘤功效的兴趣。这些研究使我们合成了各种亲脂性的新CP衍生物，并评估了它们在五种人类癌细胞系中的活性。通过简单和成本有效的方法，制备了31种CP的7-（（4-取代的）哌嗪-1-基）衍生物，其显示出从μ M至mM浓度的IC 50值，并且在健康小鼠中体内无毒，如其最大耐受剂量（MTD）指数>80 mg/kg所示。几个衍生物显示出更高的体外抗肿瘤活性比母CP，但这是不依赖于亲脂性的取代基。在所有合成的衍生物中，2和6 h的活性最强，其IC_（50）值分别为
Ciprofloxacin (CP), an antibiotic has been shown to have antiproliferative and apoptotic activities in several cancer cell lines. Moreover, several reports have highlighted the interest of increasing the lipophilicity to improve the antitumor efficacy. These studies have led us to synthesize new CP derivatives of various lipophilicities and to evaluate their activity in five human cancer cell lines. With an easy and cost-efficient procedure, 31 7-((4-substituted)piperazin-1-yl) derivatives of CP were prepared that displayed IC50 values ranging from mu M to mM concentrations and are non-toxic in vivo in healthy mice as shown by their maximal tolerated dose (MTD) indices >80 mg/kg. Several derivatives displayed higher in vitro antitumor activity than parent CP however this was not dependent on the lipophilicity of the substituent. Among all synthesized derivatives, the most potent were 2 and 6h whose IC50 values were