...
首页> 外文期刊>Journal of Medicinal Chemistry >3-aryl-2-quinolone derivatives: synthesis and characterization of in vitro and in vivo antitumor effects with emphasis on a new therapeutical target connected with cell migration.
【24h】

3-aryl-2-quinolone derivatives: synthesis and characterization of in vitro and in vivo antitumor effects with emphasis on a new therapeutical target connected with cell migration.

机译:3-芳基-2-喹诺酮衍生物:体外和体内抗肿瘤作用的合成和表征,重点是与细胞迁移有关的新治疗靶标。

获取原文
获取原文并翻译 | 示例
           

摘要

Among 25 3-aryl-2-quinolone derivatives synthesized, the antitumor activity of some of them was characterized both in vitro and in vivo. In this series, no compound appeared to be cytotoxic in vitro, as was known by the colorimetric MTT assay carried out on 12 distinct human cancer cell lines obtained from the American Type Culture Collection. Indeed, the concentration values decreasing the growth of the 12 cell lines by at least 50% (IC(50) index) were always higher than 10(-5) M. We then made use of a computer-assisted phase-contrast videomicroscopy system to quantitatively determine in vitro the level of migration of living MCF-7 human breast cancer cells. For example, at 10(-7) M, compounds 7, 13, 16, and 28 markedly decreased the migration level of these MCF-7 human breast cancer cells. The in vivo determination of the maximum tolerated dose showed that all compounds tested were definitively nontoxic. When the nontoxic, antimigratory compound 16 was combined with either doxorubicin or etoposide, two cytotoxic compounds routinely used in the clinic, this led to additive in vivo benefits from this treatment (as compared to individual administrations of the drugs) when the MXT mouse mammary adenocarcinoma was used. Thus, nontoxic antimigratory compounds, including the 2-quinolone derivatives synthesized here, can actually improve the efficiency of antitumor treatment when combined with conventional cytotoxic agents.
机译:在合成的25种3-芳基-2-喹诺酮衍生物中,其中一些的抗肿瘤活性已在体内和体外进行了表征。在该系列中,没有化合物表现出体外细胞毒性,这是通过对从美国典型培养物保藏中心获得的12种不同的人类癌细胞系进行的比色MTT分析得知的。实际上,将12种细胞系的生长降低至少50%(IC(50)指数)的浓度值始终高于10(-5)M。然后,我们使用了计算机辅助相衬视频显微镜系统以定量确定活的MCF-7人乳腺癌细胞的迁移水平。例如,在10(-7)M时,化合物7、13、16和28显着降低了这些MCF-7人乳腺癌细胞的迁移水平。体内最大耐受剂量的测定表明,所有测试的化合物绝对无毒。当无毒,抗迁移化合物16与阿霉素或依托泊苷(临床上常规使用的两种细胞毒性化合物)组合使用时,当MXT小鼠乳腺腺癌时,这种治疗(与单独给药相比)可从该治疗中获得更多的体内益处被使用了。因此,当与常规细胞毒剂组合时,无毒的抗迁移化合物,包括在此合成的2-喹诺酮衍生物,实际上可以提高抗肿瘤治疗的效率。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号