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

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, resp. The alkene complexes 2c-5c and their precursors: ketones 2a-5a and alcs. 2b-5b were characterized by NMR and IR spectroscopy, mass spectrometry, and elemental anal. The mol. structures of the intermediates 2b and 4a were detd. by single-crystal x-ray structure anal. In the solid state, two mols. of 2b or 4a form a dimeric structure, which is held together by strong H bonds. Compds. 2c-5c were also studied by cyclic voltammetry (CV). The ferrocenyl-uracil derivs. 2c-4c revealed reversible uncomplicated oxidns., whereas the cyclic voltammogram of the ruthenocenyl deriv. 5c showed an irreversible oxidn. Compds. 2c-5c were tested for their antiproliferative activity against human MCF-7 breast adenocarcinoma and HT-29 colon carcinoma cells. Compds. 3c-5c were moderately active against MCF-7 cancerous cells. Atomic absorption spectroscopy measurements on compd. 5c revealed that the ruthenocenyl deriv. is taken up by HT-29 cells in a time-dependent manner. However, the Ru cellular level remains relatively low. Compds. 2a-5a were also tested against Gram-pos. methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and Staphylococcus epidermidis bacterial strains. Compd. 4a showed significant antibacterial activity against all bacterial strains, while compds. 2a and 3b were only moderately active. No antibacterial activity was found for the ruthenocenyl deriv. 5a. [on SciFinder(R)]