University of Puerto Rico, Department of Chemistry, Mayaguez,, Puerto Rico.
Toxicol In Vitro. 2010 Feb;24(1):178-83. doi: 10.1016/j.tiv.2009.09.010. Epub 2009 Sep 20.
Replacement of the ancillary ligand in titanocene dichloride by amino acids provides titanocene species with high water solubility. As part of our research efforts in the area of titanium-based antitumor agents, we have investigated the cytotoxic activity of Cp(2)TiCl(2) and three water soluble titanocene-amino acid complexes - [Cp(2)Ti(aa)(2)]Cl(2) (aa=L-cysteine, L-methionine, and D-penicillamine) and one water soluble coordination compound, [Ti(4)(maltolato)(8)(micro-O)(4)] on the human colon adenocarcinoma cell line, Caco-2. At pH of 7.4 all titanocene species decompose extensively while [Ti(4)(maltolato)(8)(micro-O)(4)] is stable for over seven days. In terms of cytotoxicity, the [Cp(2)Ti(aa)(2)]Cl(2) and [Ti(4)(maltolato)(8)(micro-O)(4)] complexes exhibited slightly higher toxicity than titanocene dichloride at 24h, but at 72h titanocene dichloride and [Ti(4)(maltolato)(8)(micro-O)(4)] have higher cytotoxic activity. Cellular titanium uptake was quantified at various time intervals to investigate the possible relationship between Ti uptake and cellular toxicity. Results indicated that there was not a clear relationship between Ti uptake and cytotoxicity. A structure-activity relationship is discussed.
取代二氯二茂钛中的辅助配体为氨基酸，可使二茂钛物种具有高水溶性。在我们对基于钛的抗肿瘤剂的研究工作中，我们研究了 Cp(2)TiCl(2) 和三种水溶性二茂钛-氨基酸配合物-[Cp(2)Ti(aa)(2)]Cl(2)（aa=L-半胱氨酸、L-蛋氨酸和 D-青霉胺）和一种水溶性配位化合物[Ti(4)(maltolato)(8)(micro-O)(4)]对人结肠腺癌细胞系 Caco-2 的细胞毒性活性。在 pH 为 7.4 时，所有二茂钛物种都广泛分解，而[Ti(4)(maltolato)(8)(micro-O)(4)]在超过七天的时间内稳定存在。就细胞毒性而言，[Cp(2)Ti(aa)(2)]Cl(2)和[Ti(4)(maltolato)(8)(micro-O)(4)]配合物在 24 小时时比二茂钛二氯化物具有略高的毒性，但在 72 小时时，二茂钛二氯化物和[Ti(4)(maltolato)(8)(micro-O)(4)]具有更高的细胞毒性活性。在不同时间间隔量化细胞内钛摄取量，以研究钛摄取与细胞毒性之间的可能关系。结果表明，钛摄取与细胞毒性之间没有明显的关系。讨论了结构-活性关系。
