Hickey Thomas, Claffey James, Fitzpatrick Eoin, Hogan Megan, Pampillón Clara, Tacke Matthias
Conway Institute of Biomolecular and Biomedical Research, The UCD School of Chemistry and Chemical Biology, Centre for Synthesis and Chemical Biology (CSCB), University College Dublin, Belfield, Dublin 4, Ireland.
Invest New Drugs. 2007 Oct;25(5):425-33. doi: 10.1007/s10637-007-9061-8. Epub 2007 May 22.
From the carbolithiation of 6-N,N-dimethylamino fulvene (3a) and different lithiated N-heterocyclic compounds (N,N-dimethylaminomethylpyrrole, 1-methylimidazole and 2,4-[bis(N',N'-dimethylaminomethyl)]-N-methyl pyrrole), the corresponding lithium cyclopentadienide intermediate (4a-c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4 resulting in dimethylamino-functionalised titanocenes 5a-c. When these titanocenes were tested against LLC-PK cells, the IC50 values obtained were of 13, and 63 microM for titanocenes 5b and 5c, respectively. The most cytotoxic titanocene in this paper (5a) with an IC50 value of 6.8 microM is found to be almost as cytotoxic as cis-platin, which showed an IC50 value of 3.3 microM, when tested on the epithelial pig kidney LLC-PK cell line, and titanocene 5c is approximately 400 times better than titanocene dichloride itself.
由6-N，N-二甲基氨基富烯（3a）与不同的锂化N-杂环化合物（N，N-二甲基氨基甲基吡咯、1-甲基咪唑和2,4-[双（N'，N'-二甲基氨基甲基）]-N-甲基吡咯）进行碳锂化反应，生成了相应的环戊二烯基锂中间体（4a - c）。这三种锂化中间体与TiCl4发生金属转移反应，生成了二甲基氨基官能化的钛茂5a - c。当用这些钛茂对LLC - PK细胞进行测试时，所得到的IC50值分别为：钛茂5b为13 μM，钛茂5c为63 μM。本文中细胞毒性最大的钛茂（5a），其IC50值为6.8 μM，发现在对猪肾上皮LLC - PK细胞系进行测试时，其细胞毒性几乎与顺铂相当，顺铂的IC50值为3.3 μM，并且钛茂5c比二氯钛茂本身的细胞毒性大约高400倍。
