...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Dalton transactions: An international journal of inorganic chemistry >Speciation in human blood of Metvan, a vanadium based potential anti-tumor drug
【24h】

Speciation in human blood of Metvan, a vanadium based potential anti-tumor drug

机译：Metvan人类血液的形态，基于钒的潜在抗肿瘤药物

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The first report on the anti-cancer activity of the compound Metvan, [(VO)-O-IV(Me(2)phen)(2)(SO4)], where Me(2)phen is 4,7-dimethyl-1,10-phenanthroline, dates back to 2001. Although it was immediately identified as one of the most promising multitargeted anti-cancer V compounds, no development on the medical experimentation was carried out. One of the possible reasons is the lack of information on its speciation in aqueous solution and its thermodynamic stability, factors which influence the transport in the blood and the final form which reaches the target organs. To fill this gap, in this work the speciation of Metvan in aqueous solution and human blood was studied by instrumental (EPR, electronic absorption spectroscopy, ESI-MS and ESI-MS/MS), analytical (pH-potentiometry) and computational (DFT) methods. The results suggested that Metvan transforms at physiological pH into the hydrolytic species cis-[VO(Me(2)phen)(2)(OH)](+) and that both citrate and proteins (transferrin and albumin in the blood serum, and hemoglobin in the erythrocytes) form mixed complexes, denoted [VO(Me(2)phen)(citrH(-1))](2-) and VOMe(2)phen-Protein with the probable binding of His-N donors. The measurements with erythrocytes suggest that Metvan is able to cross their membrane forming mixed species VO-Me(2)phen-Hb. The redox stability in cell culture medium was also examined, showing that ca. 60% is oxidized to V-V after 5 h. Overall, the speciation of Metvan in the blood mainly depends on the V concentration: when it is larger than 50 mu M, [VO(Me(2)phen)(citrH(-1))](2-) and VO-Me(2)phen-Protein are the major species, while for concentrations lower than 10 mu M, (VO)(hTf) is formed and Me2phen is lost. Therefore, it is plausible that the pharmacological activity of Metvan could be due to the synergic action of free Me2phen, and VIVO and (VO)-O-V/(VO2)-O-V species.
机译：关于化合物Metvan的抗癌活性的第一报告，[（VO）-O-IV（Me（2）pen）（2）（2）（SO 4）]，其中Me（2）phen是4,7-二甲基 - 1,10-菲咯啉，返回2001年。虽然它立即被鉴定为最有前途的多元抗癌v化合物之一，但没有对医学实验进行的开发。其中一种可能的原因是缺乏关于其水溶液的形态的信息及其热力学稳定性，影响血液中运输的因素和到达目标器官的最终形式。为了填补这种差距，在这项工作中，通过仪器（EPR，电子吸收光谱，ESI-MS和ESI-MS / MS），分析（pH-电位测量）和计算（DFT）研究了水溶液和人血液中的Metvan和人血液的形态。 ） 方法。结果表明，METVAN在生理pH中转化为水解物种CIS-[VO（ME（2）pen）（2）（2）（OH）]（+），并且柠檬酸盐和蛋白质（血液中的转移素和白蛋白，和红细胞中的血红蛋白）形成混合复合物，表示[VO（2）phen）（CitrH（-1））]（2-）和vome（2）的Phen-蛋白，其具有His-N施主的可能结合。用红细胞的测量表明，Metvan能够穿过其膜形成混合物种VO-ME（2）ph-Hb。还检查了细胞培养基中的氧化还原稳定性，显示了CA. 5小时后，60％被氧化成V-V。总体而言，血液中的Metvan的形态主要取决于V浓度：当它大于50 mu m时，[vo（me（2）pen）（citrh（-1））]（2-）和vo-me （2）Phen-蛋白是主要物种，而对于低于10μm的浓度，形成（Vo）（HTF），并且Me2phen丢失。因此，Metvan的药理活性可能是由于自由Me2phen的协同作用和体内和（VO）-O-V /（VO2）-V / v物种。

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