Copper(II) Complexes with Highly Water-Soluble l- and d-Proline鈥揟hiosemicarbazone Conjugates as Potential Inhibitors of Topoisomerase II伪

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• 作者：Felix Bacher ; 脡va A. Enyedy ; N贸ra V. Nagy ; Antal Rockenbauer ; Gabriella M. Bogn谩r ; Robert Trondl ; Maria S. Novak ; Erik Klapproth ; Tam谩s Kiss ; Vladimir B. Arion
• 刊名：Inorganic Chemistry
• 出版年：2013
• 出版时间：August 5, 2013
• 年：2013
• 卷：52
• 期：15
• 页码：8895-8908
• 全文大小：588K
• 年卷期：v.52,no.15(August 5, 2013)
• ISSN：1520-510X

文摘

Two proline鈥搕hiosemicarbazone bioconjugates with excellent aqueous solubility, namely, 3-methyl-(S)-pyrrolidine-2-carboxylate-2-formylpyridine thiosemicarbazone [l-Pro-FTSC or (S)-H₂L] and 3-methyl-(R)-pyrrolidine-2-carboxylate-2-formylpyridine thiosemicarbazone [d-Pro-FTSC or (R)-H₂L], have been synthesized and characterized by elemental analysis, one- and two-dimensional ¹H and ¹³C NMR spectroscopy, and electrospray ionization mass spectrometry. The complexation behavior of l-Pro-FTSC with copper(II) in an aqueous solution and in a 30% (w/w) dimethyl sulfoxide/water mixture has been studied via pH potentiometry, UV鈥搗is spectrophotometry, electron paramagnetic resonance, ¹H NMR spectroscopy, and spectrofluorimetry. By the reaction of copper(II) acetate with (S)-H₂L and (R)-H₂L in water, the complexes [Cu(S,R)-L] and [Cu(R,S)-L] have been synthesized and comprehensively characterized. An X-ray diffraction study of [Cu(S,R)-L] showed the formation of a square-pyramidal complex, with the bioconjugate acting as a pentadentate ligand. Both copper(II) complexes displayed antiproliferative activity in CH1 ovarian carcinoma cells and inhibited Topoisomerase II伪 activity in a DNA plasmid relaxation assay.