Ferrocenes (F168, F169) and Fero-Sorbitol-Citrate (FSC): Potential Anticancer Drugs

Abstract

We have shown earlier that the iron containing, ferric-sorbitol-citrate complex (FSC) inhibited proliferation of cultured mouse melanoma B16, GHC, KB, HeLa and CaCo2 cells and caused mouse melanoma regression in vivo. This drug did not affect the proliferation of the nonmalignant fibroblast L929 line, human bone marrow-HBS, VERO and HEF cell line. It is also known, that some metallocene derivatives posses antitumour properties resulting principally from their action on the metabolism of DNA, and subsequently, RNA and proteins. We synthesized in our laboratory some ferrocene analogs (F168 and F169) and tested their antiproliferative ability for malignant human carcinoma Hep2 and mouse melanoma F10 cell lines. As control cell lines, human HEF and mice L929 fibroblasts were used. The tested iron substances were very potent in inhibiting the growth of malignant cell lines, whereas they had no significant inhibitory effect on the viability of nonmalignant fibroblasts. The most pronounced growth inhibitory and cytotoxic effect was found in the malignant F10 cells and the most potent was ferrocene F169. Because of their selective effect on malignant cells, the ferric-sorbitol-citrate complex as well as tested ferrocenes will be further investigated and submitted as new antitumour substances.

Development of Iron-Containing Multiwalled Carbon Nanotubes for MR-Guided Laser-Induced Thermotherapy

“…By introducing increasing masses of ferrocene (60, 200, 400 and 600 mg) during synthesis, we hypothesized that more iron would become entrapped in the nanotubes. Although ferrocene is being investigated as an anticancer agent [29,30], some concern exists regarding potential toxicity following chronic exposure to ferrocene [31,32]. Therefore, MWCNTs were washed by ultrasonication for 20 h in sulfuric and nitric acid (3:1) following synthesis to eliminate iron contaminants on the outside, reducing any potential toxic side effects and ensuring that the ferrocene would remain colocalized with the MWCNTs.…”

Organometallic Complexes: New Tools for Chemotherapy

“…From this observation, it was proposed that ferrocenyl compounds could be oxidized in vivo, and both, ferricinium and ferrocene, could be responsible for the cytotoxic effects [60]. As a result, ferrocene was incorporated into a large number of molecules such as water soluble polymers [61][62][63][64], DNA intercalator [65], phosphino compounds [66][67][68][69], and other biomolecules [70][71][72][73]. Diferrocenyl compounds [74] and a variety of other small ferrocenyl molecules [75][76][77][78][79] have also been investigated for anticancer activity.…”

Synthesis, structure and in vitro cytostatic activity of ferrocene—Cinchona hybrids

“…For instance, ferrocenylprop-2-en-1-ones were also demonstrated to strongly inhibit the HepG2 cells while having no toxicity towards healthy human fibroblasts. 8 The potential of simple ferrocene-based heterocycles in fighting cancer,ferrocenylalkyl-substituted azoles were also found to exhibit in vivo antitumor activity presenting up to 100% of tumour growth inhibition associated with lower toxicity when compared to clinically used drugs. 9 In this regard, even metalfree organic 1,4-disubstituted 1,2,3-triazoles exhibit significant antiproliferative effect against a wide range of human malignant cell lines.…”

“…The copper-mediated [2+3] cycloaddition of azidoferrocene (8), azidomethylferrocene (9) and 1,1'-bis(azidomethyl)ferrocene (10) with alkynes 1a,b conducted under the conditions of Method i resulted in the formation of a set of triazoles of types 12-15 as chalchone-free models. In spite of the low catalyst loading, the majority of these click reactions afforded triazole-tethered hybrids in mediocre yields (78% for 12c; 87% for 13d and 64% for 14d along with azidomethyl compound 15d in low yield (16%)), each of them incorporating cinchona residue with reversed configuration at the C9 stereogenic center.…”