Gay Marina, Montaña Angel M, Moreno Virtudes, Prieto María-José, Pérez José Manuel, Alonso Carlos
Department of Organic Chemistry, Universidad de Barcelona, Campus de Pedralbes, Spain.
Bioorg Med Chem. 2006 Mar 1;14(5):1565-72. doi: 10.1016/j.bmc.2005.10.016. Epub 2005 Oct 25.
The studies of interaction with DNA and the cytotoxic activity of a new organometallic platinum(II) compound are presented. The ability of this new platinum complex to modify secondary DNA structure was explored by circular dichroism (CD). Electrophoretic mobility showed changes in tertiary DNA structure, and atomic force microscopy (AFM) revealed morphological changes of plasmid DNA (pBR322). This compound breaks the traditional structure-activity rules for cis-platinum compounds, but it could be of interest because of its different kinetics. An organometallic bond normally shows a trans-effect higher than that of an amine ligand, and that fact, a priori, could contribute to a higher DNA binding rate. Several ovarian cancer cell lines, resistant and non-resistant to cisplatin, were exposed to increasing concentrations of cisplatin and complex 5 for 24 h, after which time the cell number/viability was determined by the colorimetric MTT assay. A lower cytotoxicity but also a lower resistant factor was observed for organometallic compound 5 than for cisplatin, against A2780 and A2780cisR cell lines. This result is consistent with the DNA interaction degree observed by the aforementioned techniques.
本文介绍了一种新型有机金属铂（II）化合物与DNA的相互作用及其细胞毒性活性的研究。通过圆二色性（CD）研究了这种新型铂配合物修饰DNA二级结构的能力。电泳迁移率显示了DNA三级结构的变化，原子力显微镜（AFM）揭示了质粒DNA（pBR322）的形态变化。该化合物打破了顺铂化合物的传统构效关系规则，但因其不同的动力学性质可能具有研究价值。有机金属键通常显示出比胺配体更高的反位效应，从先验角度来看，这一事实可能有助于提高DNA结合速率。将几种对顺铂耐药和不耐药的卵巢癌细胞系暴露于浓度递增的顺铂和配合物5中24小时，之后通过比色法MTT测定法确定细胞数量/活力。对于A2780和A2780cisR细胞系，观察到有机金属化合物5的细胞毒性低于顺铂，耐药因子也更低。这一结果与上述技术观察到的DNA相互作用程度一致。
