Synthesis and characterization of new ferrocenyl compounds with different alkyl chain lengths and functional groups to target breast cancer cells

• New adipic and succinic ferrocifen derivatives were synthesized.
• Cytotoxicity of ferrocifen-type amides is not dependent on the chain length.
• FcTAM-type primary amides are slightly more active than hydroxamides.
• A ferrocenic succinimide showed the best activities against MCF-7 cells.
• MCF-7 and MDA-MB-231 cells are differently sensitive to the effects of compounds.

A new family of organometallic compounds bearing chains of different lengths and with different functional groups was synthesized and evaluated against triple negative MDA-MB-231 and hormone-dependent MCF-7 breast cancer cells. Biological results comparing suberamides (six-methylene chain length) and succinamides (two methylene chain length) showed that chain shortening does not dramatically impact on their antiproliferative effects. Cytotoxicity of primary amides is not dependent on chain length, as suberamide and succinamide showed almost identical activity against both types of breast cancer cells. However, the possibility that some of the cytotoxic activity of hydroxamides could be related to enzyme inhibition, e.g. histone deacetylase (HDAC) inhibition, is not excluded. This is based on the fact that compounds bearing a longer alkyl chain showed IC50 values lower than those with shorter alkyl chains. Succinic and adipic carboxylic acids and a succinimide were also tested and they also showed cytotoxic activity. Interestingly, succinimide was the most active compound against hormone-dependent MCF-7 breast cancer cells, presumably owing to an antagonist effect with the alpha form of the estrogen receptor (ERα). Some new and interesting side chain influences related to antiproliferative effects can therefore be observed.

A new family of hydroxamides, amides and carboxylic acids derived from the adipic and succinic acids and bearing the motif 4-(2-ferrocenyl-1-phenylbut-1-en-1-yl)phenyl of ferrocifen was synthesized evaluated against cancer cells.Figure optionsDownload as PowerPoint slide