Ferrocenylvinyl-flavones: Synthesis, structure, anticancer and antibacterial activity studies

• Synthesis of ferrocenyl-flavones via Heck reaction.
• Ferrocenyl-flavones show cytotoxicity against CCRF-CEM cell line.
• Cytotoxic activity is related to apoptosis induction.
• One of the ferrocenyl-flavones shows significant antibacterial activity against Gram-positive bacterial strains.

Four new ferrocenyl-flavone complexes were obtained via palladium-catalyzed Heck cross-coupling reactions; (E)-6-ferrocenylvinyl-chromen-4-one (4), (E)-6-ferrocenylvinyl-2-methyl-chromen-4-one (5), (E)-6-ferrocenylvinyl-2-phenyl-chromen-4-one (6) and (E)-6-ferrocenylvinyl-chromen-4-one-3-propionic acid (7). All compounds were characterized by 1H NMR, 13C NMR, IR spectroscopy, high resolution-MS, elemental analysis and cyclic voltammetry. The molecular structure of derivatives 4 and 6 was also confirmed by X-ray crystallography. The biological activity of the complexes was rationalized on the basis of their anticancer and antibacterial properties. The anticancer activity of ferrocenyl-flavones 4–7 against established human cell lines derived from hematological and solid tumors has been evaluated in vitro. The following cell lines were investigated: MCF-7 (estrogen receptor-responsive breast adenocarcinoma), MDA-MB-231 (estrogen receptor-negative breast adenocarcinoma), HepG2 (hepatocellular carcinoma) and CCRF-CEM (T lymphoblast-like polymorph cells). All investigated ferrocenyl-flavones show cytotoxicity against CCRF-CEM cell line. The antibacterial activity of the four ferrocenyl-flavones against Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-resistant S. aureus (VRSA) and Staphylococcus epidermidis bacterial strains was determined. Our experiments show antibacterial activity for the carboxylic acid derivative 7 against all tested Gram-positive bacterial strains while no activity was detected for the ferrocene-free 6-bromo-chromen-4-one-3-propionic acid.

The Pd-catalyzed cross-coupling of vinylferrocene with 6-bromochromones afforded novel ferrocenyl-flavones. The newly obtained ferrocenyl-flavones show cytotoxicity against CCRF-CEM cancer cell line and antibacterial activity against S. aureus and S. epidermidis bacterial strains.Figure optionsDownload as PowerPoint slide