Ferrocenyl catechols: synthesis, oxidation chemistry and anti-proliferative effects on MDA-MB-231 breast cancer cells

Abstract

The synthesis and anti-tumoral properties of a series of compounds possessing a ferrocenyl group tethered to a catechol via a conjugated system is presented. On MDA-MB-231 breast cancer cell lines, the catechol compounds display a similar or greater anti-proliferative potency (IC 50 values ranging from 0.48-1.21 μM) than their corresponding phenolic analogues (0.57-12.7 μM), with the highest activity found for species incorporating the [3]ferrocenophane motif. On the electrochemical timescale, phenolic compounds appear to oxidize to the quinone methide, while catechol moieties form the o-quinone by a similar mechanism. Chemical oxidation of selected compounds with Ag 2 O confirms this interpretation and demonstrates the probable involvement of such oxidative metabolites in the in vitro activity of these species.

Synthesis of Nanoporous Carbon–Cobalt‐Oxide Hybrid Electrocatalysts by Thermal Conversion of Metal–Organic Frameworks

“…This observation suggests that the acidity of the phenol group depends on the metal, and the acidity increases in the sequence Fe < Ru < Os. By analogy with our previous investigations,39,40 this indicates that 3a undergoes a spontaneous deprotonation of the phenol function after oxidation followed by an intramolecular electron transfer between the latter and the electrogenerated osmocenium cation through the π‐conjugated system. Accordingly, under the same conditions, the cyclic voltammogram of osmocene (Cp 2 Os) remained fully reversible after the addition of phenol (Figure 3, B).…”

Scope of organometallic compounds based on transition metal-arene systems as anticancer agents: starting from the classical paradigm to targeting multiple strategies

“…215,216 Also, the long-term use of tamoxifen increases the risk of uterine and endometrial cancer because tamoxifen and its analogs are further metabolized to catechol 3,4-di hydroxytamoxifen. 217 Further, the combination of the ferrocenyl group with catechol via a conjugated system increased its in vitro anti-proliferative activity on hormone-independent (MDA-MB-231) breast cancer cells, as reported by G. Jaouen et al 218 to their corresponding phenolic analogues (0.57-12.7 mM).…”

Synthesis and biological evaluation of hydroxyl-substituted Schiff-bases containing ferrocenyl moieties

“…21 Thus, we can conclude that the presence of the ferrocenyl moiety not only increases the lipophilicity of hydroxyl-substituted Schiff-bases, but also lowers the potential of the phenoxyl radical/phenol redox couple, thus leading to high cytotoxicity. Therefore, the ferrocenyl moiety plays an intramolecular oxidation "antenna" role in the oxidation of o-dihydroxyl groups to o-quinone.…”

“…9 Ferrocene and its derivatives, because of their lipophilicity, 10,11 excellent electrochemical activity 12,13 and high stability in aqueous solution, 11,14 have received tremendous interest in pharmaceutical chemistry. [15][16][17][18][19][20][21] When incorporated into a drug, the ferrocene moiety could yield interesting results.…”