Three new asymmetric trans-amine(azole)dichloridoplatinum complexes that overcome cisplatin resistance and their reactions with 5′-GMP

详细信息    查看全文

• 作者：Elena Pantoja ; Agata Gallipoli ; Steven van Zutphen ; Seiji Komeda ; Desigan Reddy ; Deogratius Jaganyi ; Martin Lutz ; Duncan M. Tooke ; Anthony L. Spek ; Carmen Navarro-Ranninger ; et al.
• 关键词：trans-Platinum ; Anticancer ; Chlorido ; Guanosine monophosphate ; Amine ; Azole
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2006
• 出版时间：December 2006
• 年：2006
• 卷：100
• 期：12
• 页码：1955-1964
• 全文大小：523 K

文摘

Three new asymmetric platinum(II) complexes comprising an isopropylamine ligand trans to an azole ligand were synthesized and fully characterized by <sup>1sup>H NMR, <sup>195sup>Pt NMR, IR and elemental analysis. In addition the X-ray crystal structure of all three complexes was determined. The reaction kinetics of the complexes with DNA model base guanosine-5′-monophosphate (GMP) was studied, revealing reaction kinetics comparable to cisplatin. To gain insight in the complexes as potential antitumor agents, cytotoxicity assays were performed on a variety of human tumor cell lines. These assays showed the complexes all to possess cytotoxicity profiles comparable to cisplatin. Furthermore, the complexes largely retain their activity in a human ovarian carcinoma cell line resistant to cisplatin, A2780R, compared to the cisplatin sensitive parent cell line A2780. These results are of fundamental importance, illustrating how platinum complexes of trans geometry can show improved activity compared to cisplatin in both cisplatin sensitive and cisplatin resistant cell lines.