Copper Complexes as Anticancer Agents

Abstract

Metal-based antitumor drugs play a relevant role in antiblastic chemotherapy. Cisplatin is regarded as one of the most effective drugs, even if severe toxicities and drug resistance phenomena limit its clinical use. Therefore, in recent years there has been a rapid expansion in research and development of novel metal-based anticancer drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. The variety of metal ion functions in biology has stimulated the development of new metallodrugs other than Pt drugs with the aim to obtain compounds acting via alternative mechanisms of action. Among non-Pt compounds, copper complexes are potentially attractive as anticancer agents. Actually, since many years a lot of researches have actively investigated copper compounds based on the assumption proposal that endogenous metals may be less toxic. It has been established that the properties of copper-coordinated compounds are largely determined by the nature of ligands and donor atoms bound to the metal ion. In this review, the most remarkable achievements in the design and development of copper(I, II) complexes as antitumor agents are discussed. Special emphasis has been focused on the identification of structure-activity relationships for the different classes of copper(I,II) complexes. This work was motivated by the observation that no comprehensive surveys of copper complexes as anticancer agents were available in the literature. Moreover, up to now, despite the enormous efforts in synthesizing different classes of copper complexes, very few data concerning the molecular basis of the mechanisms underlying their antitumor activity are available. This overview, collecting the most significant strategies adopted in the last ten years to design promising anticancer copper(I,II) compounds, would be a help to the researchers working in this field.

Synthesis, structural characterization and cytotoxic activity of ternary copper(II)–dipeptide–phenanthroline complexes. A step towards the development of new copper compounds for the treatment of cancer

“…Among the six studied complexes, [Cu(Ala-Phe)(phen)], C3, presents the higher activity, with IC 50 values comparable or lower to those presented by other complexes catalogued as promising antitumor agents [3,[38][39][40]. Moreover, C3 induces MCF-7 cell death at an IC 50 = 1 μM being more active than Cisplatin which Table 4 Wavenumber (cm −1 ) of common bands in the complexes and in the free phen, as well as their tentative vibrational assignment.…”

“…[Cu(phen) 2 ] 2+ also intercalates in the minor groove of DNA, and shows nuclease activity [9,10]. In addition, a number of heteroleptic phen-containing Cu(II) complexes show DNA binding and nuclease activity, thus preventing cellular growth [2,3]. On the other hand, Cu-dipeptide complexes, previously studied by our research group, coordinate to DNA and present some cytotoxic activity [11].…”

“…In this context, multiple Cu(II) compounds have been studied, with 1,10-phenanthroline (phen), thiosemicarbazone, or salicylate, and its derivatives as ligands, presenting many of them antitumor activity [2,3]. Outstanding examples of active Cu-complexes are the coordination compounds known as Casiopeinas®, developed by L. Ruiz and co-workers, two of which are already approved for clinical trials as antitumor drugs, [(Cu(II))(4,7-dimethyl-phen)(glycinate)(NO 3 )(H 2 O)] and [(Cu(II))(4,4′-dimethyl-2,2′-bipyridine)(acetylacetonate)(NO 3 )(H 2 O)] [4].…”

DNA damage and induction of apoptosis in pancreatic cancer cells by a new dinuclear bis(triazacyclonane) copper complex

“…The importance of Cu in anticancer therapy is demonstrated by the ever increasing group of cytotoxic Cu complexes described in the literature, with the number of papers reported in 2012 being eight times greater than in 2008 [5,6]. Several synthetic Cu complexes have been found to be active both in vitro and in vivo [4].…”

Carbohydrate– N -heterocyclic carbene metal complexes: Synthesis, catalysis and biological studies

“…Mostly studied for their catalytic activity, NHC metal complexes have also exhibited Biological activity (anti-cancer, anti-bacterial, anti-fungal, etc) has also been reported for NHC complexes of other metals, e.g., Ni [54], Ru [55,56], Ag [57,58], Cu [59], Pd [60,61].…”