Ferrocenes as potential chemotherapeutic drugs: Synthesis, cytotoxic activity, reactive oxygen species production and micronucleus assay

Abstract

Three new ferrocene complexes were synthesized with 4-(1H-pyrrol-1-yl)phenol group appended to one of the Cp ring. These are: 1,1′-4-(1H-pyrrol-1-yl)phenyl ferrocenedicarboxylate, ("Fc-(CO 2 -Ph-4-Py) 2 "), 1,4-(1H-pyrrol-1-yl)phenyl, 1′-carboxyl ferrocenecarboxylate ("Fc-(CO 2 -Ph-4-Py)CO 2 H") and 4-(1H-pyrrol-1-yl)phenyl ferroceneacetylate ("Fc-CH 2 CO 2 -Ph-4-Py"). The new species were characterized by standard analytical methods. Cyclic voltammetry experiments showed that Fc-CH 2 CO 2 -Ph-4-Py has redox potential very similar to the Fc/Fc + redox couple whereas Fc-(CO 2 -Ph-4-Py) 2 and Fc-(CO 2 -Ph-4-Py)CO 2 H have redox potentials of over 400 mV higher than Fc/Fc + redox couple. The in vitro studies on Fc-(CO 2 -Ph-4-Py) 2 and Fc-(CO 2 -Ph-4-Py)CO 2 H revealed that these two compounds have moderate anti-proliferative activity on MCF-7 breast cancer cell line. In contrast Fc-CH 2 CO 2 -Ph-4-Py which displayed low anti-proliferative activity. In the HT-29 colon cancer cell line, the new species showed low anti-proliferaive activity. Cytokinesis-block micronucleus assay (CBMN) was performed on these ferrocenes and it was determined they induce micronucleus formation on binucleated cells and moderate genotoxic effects on the MCF-7 breast cancer cell line. There is a correlation between the IC 50 values of the ferrocenes and the amount of micronucleus formation activity on binucleated cells and the reactive oxygen species (ROS) production on MCF-7 cell line.

Ferrocenyl‐Coupled N‐Heterocyclic Carbene Complexes of Gold(I): A Successful Approach to Multinuclear Anticancer Drugs

“…Reactive oxygen species are associated with the mode of action of ferrocene derivatives. There are numerous studies on the correlation between ROS production and antiproliferative effects of ferrocenes, including heteronuclear ferrocene–gold complexes . The effect of complexes 8 and 10 on the ROS levels in 518A2 melanoma cells was investigated by the nitroblue tetrazolium chloride (NBT) test (Figure A).…”

“…[40,41] We found that complexes 7b and 8 readily formed mono selenol adducts with substitution of the chloro or phosphane ligands, respectively,w hereas the biscarbene complex 10 did not (see the Supporting Information). [14,20,44] The effect of complexes 8 and 10 on the ROS levels in 518A2 melanoma cells was investigated by the nitroblue tetrazolium chloride (NBT) test (Figure5A). PARP-1 has also been identified recently as at arget for gold complexes as well as for heteronuclear iron-gold complexes.…”

“…There are numerouss tudies on the correlation between ROS production anda ntiproliferative effectso ff errocenes, including heteronuclear ferrocene-gold complexes. [14,20,44] The effect of complexes 8 and 10 on the ROS levels in 518A2 melanoma cells was investigated by the nitroblue tetrazolium chloride (NBT) test (Figure5A). When applied at lower concentrations, only complex 10 led to an increase of ROS.…”

Crystal structure of bis[4-(1H-pyrrol-1-yl)phenyl] ferrocene-1,1′-dicarboxylate: a potential chemotherapeutic drug

“…Therefore, we functionalized ferrocene with a pyrrole, 4-(1H- pyrrol-1-yl)phenol, obtaining three new ferrocenes: 1,1 0 -4-(1H-pyrrol-1-yl)phenyl ferrocenedicarboxylate, 1,4-(1Hpyrrol-1-yl)phenyl, 1 0 -carboxyl ferrocenecarboxylate (Fc-(CO 2 -Ph-4-Py)CO 2 H) and 4-(1H-pyrrol-1-yl)phenyl ferroceneacetylate (Fc-CH 2 CO 2 -Ph-4-Py). We investigated their biological activities on breast cancer cell line (MCF-7) and among these ferrocenes, 1,1 0 -4-(1H-pyrrol-1-yl)phenyl ferrocenedicarboxylate (I) was shown to be most active in this series (Pé rez et al, 2015). Nevertheless, the solid-state structure of (I) has been elusive (Pé rez et al, 2015).…”

BSA-binding studies of 2- and 4-ferrocenylbenzonitrile: voltammetric, spectroscopic and molecular docking investigations

“…The pharmacochemistry of ferrocene derivatives has attracted the attention of many scientists, and their study has been encouraged by potential biological applications [25][26][27]. Many ferrocene derivatives that have been studied in the last decade show important biological activities, such as cytotoxic [28][29][30], antimicrobial [31,32] and antitumor [33][34][35][36][37][38] activities.…”