Ferrocenyl β-Diketonate Compounds: Extended Ring Systems for Improved Anticancer Activity

• Published in: Chembiochem : a European journal of chemical biology p. e202400759
• Main Authors: Hofmann, Benjamin J, Aljohani, Enas T, Cicovacki, Natalia, Lee, Ivan, Warren, Derek T, Sobolewski, Anastasia, Stringer, Tameryn, Lord, Rianne M
• Format: Journal Article
• Language: English
• Published: Germany 24-10-2024
• Subjects: bioinorganic; acetylacetone; ferrocenyl; fluorescence; anticancer
• ISSN: 1439-4227; 1439-7633; 1439-7633
• DOI: 10.1002/cbic.202400759

A library of ferrocenyl β-diketonate compounds with varying degrees of aromatic functionality have been synthesized and fully characterized. This includes cyclic voltammetry and the analysis of four new structures by single crystal X-ray diffraction. The compounds cytotoxic potential has been determined by MTT screening against pancreatic carcinoma (MIA PaCa-2), ovarian adenocarcinoma (A2780), breast adenocarcinomas (MDA-MB-231 and MCF-7) and normal epithelial retinal (ARPE-19). The compounds show a general trend, where increasing the number of aromatic rings in the molecule yields an increase in cytotoxicity and follows the trend anthracenyl > naphthyl > phenyl > methyl. The compounds are particularly sensitive to the triple negative cancer cell line MDA-MB-231, and the potential modes of action have been studied by production of reactive oxygen species using fluorescence microscopy and cell morphology using Scanning Electron Microscopy. All assays highlight the ferrocenyl β-diketonate with an anthracenyl substituent to be the lead compound in this library. The decomposition was also observed within cells, to give a cytotoxic fluorescent molecule, which has been visualized by confocal microscopy.