Ferrocifen type anti cancer drugs

Abstract

Despite current developments in therapeutics focusing on biotechnologically-oriented species, the unflagging utility of small molecules or peptides in medicine is still producing strong results. In 2014 for example, of the 41 new medicines authorized for sale, 33 belonged to the category of small molecules, while in 2013 they represented 24 of 27, according to the FDA. This can be explained as the result of recent forays into new or long-neglected areas of chemistry. Medicinal organometallic chemistry can provide us with an antimalarial against resistant parasitic strains, as attested by the phase II clinical development of ferroquine, with a new framework for conceptual advances based on three-dimensional space-filling, and with redox or indeed catalytic intracellular properties. In this context, bioferrocene species with antiproliferative potential have for several years been the subject of sustained effort, based on some initial successes and on the nature of ferrocene as a stable aromatic, with low toxicity, low cost, and possessing reversible redox properties. We show here the different antitumoral approaches offered by ferrocifen derivatives, originally simple derivatives of tamoxifen, which over the course of their development have proved to possess remarkable structural and mechanistic diversity. These entities act via various targets, some of which have been identified, that are triggered according to the concentration of the products. They also act according to the nature of the cancer cells and their functionality, by mechanistic pathways that can operate either synergistically or not, in successive, concomitant or sequential ways, depending for example on newly identified signaling pathways inducing senescence or apoptosis. Here we present a first attempt to rationalize the behavior of these entities with various anticancer targets.

Iron(III) Pincer Complexes as a Strategy for Anticancer Studies

“…[18,19] The most interesting results have been obtained with ferrocene derivatives, and in particular with the ferrocifen-type complexes. [17,[20][21][22][23][24][25] We recently prepared an iron(II) cyclometalated compound, [Fe(CO) 2 (phpy) 2 ] (phpyH = 2-phenylpyridine), and found that its activity on HTC116 and AGS cell lines was relatively moderate (IC 50 in the 25 μM range), presumably as a result of its instability in solution. [26] To stabilize the complex, while maintaining the advantages of the carbonmetal σ-bond, we considered that the use of pincer ligands would be of interest.…”

Group 11 Metal Complexes with Unsymmetrical Bifunctional Ferrocene Ligands

“…These functionalized ferrocene derivatives and their metal complexes represent an important topic of research in many fields such as organic synthesis, catalysis, asymmetric catalysis, materials chemistry, and in medicine as antimalarial or antitumor agents. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] In particular, ferrocenyl phosphines have been studied thoroughly, as represented by the well-known 1,1′-bis(diphenylphosphino)ferrocene (dppf ). [1] Some of us have described the formation of several amidephosphines containing ferrocene units, studied their coordination chemistry, [17,18] and also showed that some gold and silver complexes are active as antitumor agents.…”

Side‐Chain Effects on the 1‐(Bis‐aryl‐methylidene)‐[3]ferrocenophane Skeleton: Antiproliferative Activity against TNBC Cancer Cells and Comparison with the Acyclic Ferrocifen Series

“…Sheep uterine cytosol prepared in buffer A (0.05 M Tris-HCL, 0.25 M sucrose, 0.1 % -mercaptoethanol, pH 7.4 at 25°C) as described previously [3] was used as a source of ERα. Aliquots (200 mL) of ERα in glass tubes were incubated for 3 h at 0°C with [6, H]-E 2 (2 × 10 -9 M, specific activity 1.62 TBq/mmol, NEN Life Science, Boston, MA) in the presence of nine concentrations of the ferrocenyl complexes to be tested (between 6 × 10 -7 and 6 × 10 -9 M for the complexes with RBA values higher than 5 % and between 6 × 10 -6 and 6 × 10 -8 M for the compounds with RBA values lower than 5 %) or of 17 -E 2 (between 8 × 10 -8 and 7.5 × 10 -10 M). At the end of the incubation period, the fractions of [ 3 H]-E 2 bound to the estrogen receptors (Y values) were precipitated by addition of 200 mL of a cold solution of protamine sulfate (1 mg/ mL in water).…”

“…[3][4][5][6][7] In hormone-dependent cells, this effect is essentially mediated by interaction with the estradiol receptor and reversed by the addition of estradiol. In contrast, the antiproliferative effect observed in hormone-independent cells such as MDA-MB-231 cells is a cytotoxic effect.…”