Ferrocenes as potential anticancer drugs. Facts and hypotheses

Abstract

We analyzed the research data on antitumor effects of a wide range of ferrocene compounds and discussed possible mechanisms of their bioactivities. Current trends in the study of antican cer effects of ferrocene derivatives were considered. Promising ways in the design of low toxicity anticancer ferrocene based drugs of new generation were outlined. * Dedicated to the 60th anniversary of the A. N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences (INEOS RAS). The review was written on the initiative and with the active participation of Yu. S. Nekrasov who served with good faith and fidelity for INEOS RAS for more than 40 years. † Deceased.

Administration of ferrocene‐modified amino acids induces changes in synaptic transmission in the CA1 area of the hippocampus

“…Antitumor activity of ferrocene compounds is presently under active investigations, and the authors have also succeeded in this field . However, at the moment there are only a few publications on the effects of the ferrocene‐substituted compounds on the brain .…”

“…During the first two decades of the 21st century, special attention was paid to the synthesis and bioassay of ferrocene derivatives carrying pharmacophoric groups, namely, nucleic bases, oligonucleotides, various heterocycles, amino acids, peptides, and sugars . In vitro and in vivo studies have demonstrated that many of such modified ferrocenes display a wide spectrum of biological activities, including antianemic, antimicrobial, antibacterial, antimalarial, tuberculostatic, and especially antitumor activities, see recent review articles . Ferroceron (tetrahydrate of sodium salt of ortho ‐carboxybenzoyl ferrocene), which is the first and only currently ferrocene‐based drug, has been effectively used for a long time for the treatment of iron deficiency pathologies .…”

“…It is known, that iron‐containing ferrocene moiety endows the modified compounds with a number of useful properties. First, it significantly decreases their toxicity and improve their lipid membrane penetrating ability . Moreover, it allows there compounds to exist both in salt and neutral forms providing their transport in a blood flow, as well as across the membranes into cytoplasm (polar medium).…”

“…For instance, it is known that GABA, being a major mediator involved in the central inhibition processes activates the energetic processes in the brain, scarcely penetrates across the blood‐brain barrier (BBB) and only as small as 8% of GABA‐containing drug aminalon reaches the brain targets upon oral administration. A ferrocene moiety which is generally agreed to be a good vehicle overcomes readily the BBB (though this hypothesis did not find sufficient experimental support) and can facilitate the targeted drug delivery to the brain. Authors conclude that administration of the lipophilic iron‐containing ferrocene compound leads to subtle perturbations of cellular iron within the brain, potentially representing a model of iron accumulation similar to that seen in various neuropathological conditions.…”

[3+2]-Cycloaddition Reaction between Tetraphenylporphyrinylazide and Ferrocenyl Dipolarophiles

“…[1] Ferrocenylheterocyclic compounds have been found to exhibit a wide range of biological activities (e.g. antitumor [2,3] and antimicrobial [4] ). Ferrocene containing porphyrins have already been synthesized by various synthetic methods.…”