Rakić Gordana M, Grgurić-Sipka Sanja, Kaluderović Goran N, Gómez-Ruiz Santiago, Bjelogrlić Snezana K, Radulović Sinisa S, Tesić Zivoslav Lj
Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
Eur J Med Chem. 2009 May;44(5):1921-5. doi: 10.1016/j.ejmech.2008.11.004. Epub 2008 Nov 19.
Novel complexes of platinum(II) with 3- (1) or 4-acetylpyridine (2) have been synthesized and characterized by elemental analyses, IR, (1)H and (13)C NMR spectroscopy. Single crystal X-ray diffraction revealed the trans geometry of complex 2. DFT calculations confirm formation of trans isomers for both complexes. The complexes have been tested for their cytotoxicity against HeLa (human cervical cancer), U2OS (human osteosarcoma), U2OScisR (human osteosarcoma cisplatin resistant), B16 (murine melanoma), MDA-453, MDA-361, and MCF-7 (human breast cancer), LS-174 (human colon cancer) and FemX (human melanoma) cell lines. The most promising compound trans-dichloridobis(4-acetylpyridine)platinum(II) (2) overcomes cisplatin resistance of U2OScisR cells after 48h of drug exposure.
已合成了铂（II）与3-（1）或4-乙酰基吡啶（2）形成的新型配合物，并通过元素分析、红外光谱、（1）H和（13）C核磁共振光谱对其进行了表征。单晶X射线衍射表明配合物2具有反式几何结构。密度泛函理论计算证实两种配合物均形成反式异构体。已测试了这些配合物对HeLa（人宫颈癌）、U2OS（人骨肉瘤）、U2OScisR（人顺铂耐药骨肉瘤）、B16（鼠黑色素瘤）、MDA-453、MDA-361和MCF-7（人乳腺癌）、LS-174（人结肠癌）和FemX（人黑色素瘤）细胞系的细胞毒性。最有前景的化合物反式二氯双（4-乙酰基吡啶）铂（II）（2）在药物暴露48小时后克服了U2OScisR细胞的顺铂耐药性。
