Metallocene-Modified Uracils: Synthesis, Structure, and Biological Activity

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• 作者：Konrad Kowalski ; Joanna Skiba ; Luciano Oehninger ; Ingo Ott ; Jolanta Solecka ; Aleksandra Rajnisz ; Bruno Therrien
• 刊名：Organometallics
• 出版年：2013
• 出版时间：October 28, 2013
• 年：2013
• 卷：32
• 期：20
• 页码：5766-5773
• 全文大小：353K
• 年卷期：v.32,no.20(October 28, 2013)
• ISSN：1520-6041

文摘

A new family of metallocene鈥搖racil conjugates, including [3-(N1-uracilyl)-1-(ferrocenyl)]propene (2c), [3-(N1-thyminyl)-1-(ferrocenyl)]propene (3c), [3-(N1-(5-fluorouracilyl))-1-(ferrocenyl)]propene (4c), and [3-(N1-uracilyl)-1-(ruthenocenyl)]propene (5c), was obtained in three steps from (3-chloropropionyl)ferrocene and (3-chloropropionyl)ruthenocene, respectively. The complexes 2c鈥?b>5c and their intermediates 2a鈥?b>5a and 2b鈥?b>5b were characterized by NMR and infrared spectroscopy, mass spectrometry, and elemental analysis. The molecular structures of the intermediates 2b and 4a were determined by single-crystal X-ray structure analysis. In the solid state, two molecules of 2b or 4a form a dimeric structure, which is held together by strong hydrogen bonds. Compounds 2c鈥?b>5c were also studied by cyclic voltammetry (CV). The ferrocenyl鈥搖racil derivatives 2c鈥?b>4c revealed reversible uncomplicated oxidations, whereas the cyclic voltammogram of the ruthenocenyl derivative 5c showed an irreversible oxidation. Compounds 2c鈥?b>5c were tested for their antiproliferative activity against human MCF-7 breast adenocarcinoma and HT-29 colon carcinoma cells. Compounds 3c鈥?b>5c were moderately active against MCF-7 cancerous cells. Atomic absorption spectroscopy measurements on compound 5c revealed that the ruthenocenyl derivative is taken up by HT-29 cells in a time-dependent manner. However, the ruthenium cellular level remains relatively low. Compounds 2a鈥?b>5a were also tested against Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and Staphylococcus epidermidis bacterial strains. Compound 4a showed significant antibacterial activity against all bacterial strains, while compounds 2a and 3b were only moderately active. No antibacterial activity was found for the ruthenocenyl derivative 5a.