N-Heterocyclic Carbene Iron Complexes as Anticancer Agents: In Vitro and In Vivo Biological Studies

Cisplatin and its derivatives are commonly used in chemotherapeutic treatments of cancer, even though they suffer from many toxic side effects. The problems that emerge from the use of these metal compounds led to the search for new complexes capable to overcome the toxic side effects. Here, we report the evaluation of the antiproliferative activity of Fe(II) cyclopentadienyl complexes bearing n-heterocyclic carbene ligands in tumour cells and their in vivo toxicological profile. The in vitro antiproliferative assays demonstrated that complex Fe1 displays the highest cytotoxic activity both in human colorectal carcinoma cells (HCT116) and ovarian carcinoma cells (A2780) with IC50 values in the low micromolar range. The antiproliferative effect of Fe1 was even higher than cisplatin. Interestingly, Fe1 showed low in vivo toxicity, and in vivo analyses of Fe1 and Fe2 compounds using colorectal HCT116 zebrafish xenograft showed that both reduce the proliferation of human HCT116 colorectal cancer cells in vivo.

POLYMERIZATION OF METHYL METHACRYLATE IN PRESENCE OF INITIATING SYSTEMS BASED ON IRON COMPLEXES OF VARIOUS STRUCTURES

The features of the radical polymeriation of methyl methacrylate using initiating systems based on benzoyl peroxide and iron complexes with various ligand environments, including ferrocenes containing electron-donating and electron-withdrawing substituents in cyclopentadienyl rings, as well as cyclopentadienyl carbonyl-containing derivatives of iron, have been studied. The influence of the structure of iron complexes on the kinetics of the radical polymerization of methimethacrylate, as well as the molecular weight characteristics of the synthesized polymers, was estimated. It was established that, according to the effect on the methylmethacrylate polymerization rate in the presence of the initiating systems under study, the metal complexes are arranged in the series: 1,1'-dibromoferrocene, bromo (η5-cyclopentadienyl)dicarbonyl iron>1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino- ferrocene)>ferrocene>1-di-tert-butylphosphinoferrocene>1,1-bis-di-tert-butyl-phosphino-ferrocene> bis (η5-cyclopentadienyl) dicarbonyl iron>1–bromo-1′- diphenyl phosphino ferrocene>1-diphenylphosphino-1'-di-tert-butylphosphinoferrocene. Polymers based on polymethylmethacrylate synthesized in the presence of the studied cyclopentadienyl complexes of iron and benzoyl peroxide are capable of acting as macroinitiators in postpolymerization processes. In particular, it was found that polymethylmethacrylate synthesized with the participation of 1,1′-dibromoferrocene and bromo (η5-cyclopentadienyl) dicarbonyl iron in the presence of a peroxide initiator allows the synthesis of postpolymers. Using NMR spectroscopy, it was found that methyl methacrylate-based polymers synthesized both in the presence of the above iron complexes and its analogs obtained by traditional radical polymerization have an atactic structure. Using differential scanning calorimetry, it was shown that methyl methacrylate-based polymers obtained in the presence of cyclopentadienyl and carbonyl iron complexes have a higher glass transition temperature compared to similar polymers synthesized by radical polymerization involving only the peroxide initiator. The temperature of the onset of decomposition of these polymers remains almost unchanged.

Antimicrobial properties of half-sandwich Ir(iii) cyclopentadienyl complexes with pyridylbenzimidazole ligands

Ethyl group determined the toxicity of pyridylbenzimidazole Ir(iii) compounds and exchange of the group with sulfonate led to diminishing of the antibacterial activity. Increasing the metal content per complex, 3, gave rise to a compound with no toxicity.

Antitumour and Toxicity Evaluation of a Ru(II)-Cyclopentadienyl Complex in a Prostate Cancer Model by Imaging Tools

Background: Ruthenium complexes have been extensively investigated for their prospective value as alternatives to cisplatin. Recently, we reported the in vitro anticancer properties of a family of organometallic ruthenium( II)-cyclopentadienyl complexes and have explored their mechanism of action. Objective: The purpose of this study was to evaluate the in vivo antitumour efficacy and toxicity of one of these Ru(II) compounds, [RuCp(mTPPMSNa)(2,2′-bipy)][CF3SO2] (TM85) which displayed an interesting spectrum of activity against several cancer cells. Methods: Studies to assess the antitumour activity and toxicity were performed in a metastatic prostate (PC3) mice model using ICP-MS, nuclear microscopy, elemental analysis and Transmission Electron Microscopy (TEM). Results: TM85 showed low systemic toxicity but no significant tumour reduction, when administered at tolerated dose (20mg/kg) over 10 days. Ru was mainly retained in the liver and less in kidneys, with low accumulation in tumour. Increased bilirubin levels, anomalous Ca and Fe concentrations in liver and mitochondria alterations were indicative of liver injury. The hepatotoxicity observed was less severe than that of cisplatin and no nephrotoxicity was found. Conclusion: Under the experimental conditions of this study, TM85 is less toxic than cisplatin, induces similar tumour reduction and avoids the formation of metastatic foci. No renal toxicity was observed by the analysis of creatinine levels and the effective renal plasma flow by 99mTc-MAG3 clearance. Hence, it can be considered a valuable compound for further studies in the field of Ru-based anticancer drugs.