González V M, Amo-Ochoa P, Pérez J M, Fuertes M A, Masaguer J R, Navarro-Ranninger C, Alonso C
Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Spain.
J Inorg Biochem. 1996 Jul;63(1):57-68. doi: 10.1016/0162-0134(95)00175-1.
In the present paper, we show that the reaction of the antipyranosomatid berenil drug with K2PtCl4 resulted in the synthesis of a covalent (Pt(II)-berenil compound of formula [Pt2Cl4(berenil)2]Cl4.4H2O as shown by IR, 1H, 13C, and 195Pt-NMR. The Pt-berenil compound was tested for in vitro antitumor activity against HL-60 and U-937 human leukemic cells. The results show that the LC70 values of the Pt-berenil are about two-fold lower than those of cis-DDP in both HL-60 and U-937 cell lines. Melting data of Pt-berenil:DNA and berenil:DNA complexes indicate that the platinated compound produces on a DNA secondary structure higher compaction than the berenil ligand. The mobility in agarose gels and the circular dichroism spectra of the compounds:DNA complexes revealed, moreover, that both induce drastic changes on a DNA secondary and tertiary structure. The total reflection X-ray fluorescence data showed, in additIon that DNA platination in Pt-berenil:DNA complexes occurs within minutes after addition of the drug, in contrast to what that observed in cis-DDP:DNA complexes. On the basis of these results, we propose that in Pt-berenil, the berenil ligand acts as a carrier of the active cis-P(II) centers towards DNA.
在本论文中，我们表明，如红外光谱、¹H、¹³C和¹⁹⁵Pt核磁共振所示，抗吡喃糖体药物贝尼尔与K₂PtCl₄反应合成了一种共价（Pt(II)-贝尼尔）化合物，其化学式为[Pt₂Cl₄(贝尼尔)₂]Cl₄·4H₂O。对Pt-贝尼尔化合物针对HL-60和U-937人白血病细胞的体外抗肿瘤活性进行了测试。结果表明，在HL-60和U-937细胞系中，Pt-贝尼尔的LC₇₀值比顺铂的LC₇₀值低约两倍。Pt-贝尼尔:DNA和贝尼尔:DNA复合物的熔解数据表明，铂化化合物对DNA二级结构的压缩程度高于贝尼尔配体。此外，化合物:DNA复合物在琼脂糖凝胶中的迁移率和圆二色光谱显示，两者都会引起DNA二级和三级结构的剧烈变化。全反射X射线荧光数据还表明，与顺铂:DNA复合物中观察到的情况相反，在Pt-贝尼尔:DNA复合物中加入药物后几分钟内就会发生DNA铂化。基于这些结果，我们提出，在Pt-贝尼尔中，贝尼尔配体作为活性顺式P(II)中心向DNA的载体。
