Metallocene-Modified Uracils: Synthesis, Structure,
and Biological Activity
Posted on 2013-10-28 - 00:00
A new
family of metallocene–uracil 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–5c and their intermediates 2a–5a and 2b–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–5c were also studied by cyclic voltammetry (CV). The ferrocenyl–uracil
derivatives 2c–4c revealed reversible
uncomplicated oxidations, whereas the cyclic voltammogram of the ruthenocenyl
derivative 5c showed an irreversible oxidation. Compounds 2c–5c were tested for their antiproliferative
activity against human MCF-7 breast adenocarcinoma and HT-29 colon
carcinoma cells. Compounds 3c–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–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.
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Kowalski, Konrad; Skiba, Joanna; Oehninger, Luciano; Ott, Ingo; Solecka, Jolanta; Rajnisz, Aleksandra; et al. (2016). Metallocene-Modified Uracils: Synthesis, Structure,
and Biological Activity. ACS Publications. Collection. https://doi.org/10.1021/om400294s
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AUTHORS (7)
KK
Konrad Kowalski
JS
Joanna Skiba
LO
Luciano Oehninger
IO
Ingo Ott
JS
Jolanta Solecka
AR
Aleksandra Rajnisz
BT
Bruno Therrien
KEYWORDS
intermediates 2Biological ActivityAAtomic absorption spectroscopy measurementsCV2 bdimeric structureStaphylococcus epidermidisantiproliferative activityVRSAHTmass spectrometryCompounds 2chloropropionylcyclic voltammogramoxidationCompound 4cyclic voltammetryMSSAcompound 5 cruthenocenylcompounds 23 b5 cstrainintermediates 2 bhydrogen bondsMRSAaureusNMRMCFanalysis