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Review
. 2021 Dec 22;27(1):49.
doi: 10.3390/molecules27010049.

Copper(II) Phenanthroline-Based Complexes as Potential AntiCancer Drugs: A Walkthrough on the Mechanisms of Action

Sebastiano Masuri  1 , Petr Vaňhara  2   3 , Maria Grazia Cabiddu  1 , Lukáš Moráň  2   4 , Josef Havel  3   5 , Enzo Cadoni  1 , Tiziana Pivetta  1
Affiliations
Review

Copper(II) Phenanthroline-Based Complexes as Potential AntiCancer Drugs: A Walkthrough on the Mechanisms of Action

Sebastiano Masuri et al. Molecules. .

Abstract

Copper is an endogenous metal ion that has been studied to prepare a new antitumoral agent with less side-effects. Copper is involved as a cofactor in several enzymes, in ROS production, in the promotion of tumor progression, metastasis, and angiogenesis, and has been found at high levels in serum and tissues of several types of human cancers. Under these circumstances, two strategies are commonly followed in the development of novel anticancer Copper-based drugs: the sequestration of free Copper ions and the synthesis of Copper complexes that trigger cell death. The latter strategy has been followed in the last 40 years and many reviews have covered the anticancer properties of a broad spectrum of Copper complexes, showing that the activity of these compounds is often multi factored. In this work, we would like to focus on the anticancer properties of mixed Cu(II) complexes bearing substituted or unsubstituted 1,10-phenanthroline based ligands and different classes of inorganic and organic auxiliary ligands. For each metal complex, information regarding the tested cell lines and the mechanistic studies will be reported and discussed. The exerted action mechanisms were presented according to the auxiliary ligand/s, the metallic centers, and the increasing complexity of the compound structures.

Keywords: 1,10-phenanthroline; anticancer chemotherapy; cancer; cell stress response; chemoresistance; coordination compounds; copper.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of cisplatin (a), carboplatin (b), oxaliplatin (c), nedaplatin (d), heptaplatin (e), lobaplatin (f).
Figure 2
Figure 2
Structures of the Cu(N-N1)x(OH2)y(ClO4)z complexes.
Figure 3
Figure 3
Structures of the [Cu(LPTn)x(X)y](Y)z complexes.
Figure 4
Figure 4
Structures of the [Cu(phen)2(ITHn)](ClO4)2 (a–d) and [Cu(phen)2(SAL)](ClO4)2 (e) complexes.
Figure 5
Figure 5
Structures of the [Cu(N-N2)(DPA)](ClO4)2 complexes.
Figure 6
Figure 6
Structures of the [Cu(phen)2(CAn)](NO3)2 complexes.
Figure 7
Figure 7
Structures of the [Cu(phen)2(4-Mecdoa)] complex.
Figure 8
Figure 8
Structures of [Cu(phen)2(PHTn)] (a,b) and [Cu2(phen)4(µ-PHT3)](PHT3) (c) complexes.
Figure 9
Figure 9
Structures of the [Cu(ICAn)2(phen)] complexes.
Figure 10
Figure 10
Structures of the [Cu(indomethacin)2(5-Rphen)] complexes.
Figure 11
Figure 11
Structures of [Cu(phen)(4,5-dCl-ICA)2] (a) and [Cu(4,7-diMephen)(4,5-dCl-ICA)2] (b).
Figure 12
Figure 12
Structures of complexes [Cu(phen)(trop)(Cl)] (a) and [Cu(phen)(H4Que)(Cl)] (b).
Figure 13
Figure 13
Structure of Cas-II Gly ([Cu(4,7-diMephen)(Gly)](NO3)).
Figure 14
Figure 14
Structure of [Cu(5HTP)(phen)(H2O)](NO3).
Figure 15
Figure 15
Structures of “phen-based” [Cu(L-pro)(N-N3)(H2O)n](ClO4) complexes.
Figure 16
Figure 16
Structures of [Cu(phen)(AAn)(H2O)](NO3) complexes.
Figure 17
Figure 17
Structures of the Cu(II)–(OH-PIP) based complexes.
Figure 18
Figure 18
Structure of the [Cu(L-dipeptide)(phen)]·nH2O complexes.
Figure 19
Figure 19
Structure of the [Cu(L-dipeptide)(phen)]·nH2O complexes.
Figure 20
Figure 20
Structures of the [Cu(Sal-Gly)(N-N4)] complexes.
Figure 21
Figure 21
Structures of the phenanthroline-based [Cu(Fc-Trp)(N-N5)](ClO4) (a–c) and [Cu(Ph-Trp)(N-N5)(OH2)](ClO4) (d,e) complexes.
Figure 22
Figure 22
Structures of the [Cu(MCVH)(phen)(OH2)](ClO4) (a) and [Cu(MCLH)(phen)(OH2)](ClO4) (b) complexes.
Figure 23
Figure 23
Structures of complexes [Cu(Ly)(bathophen)](PF6) (a,b) and [Cu(tdp)(phen)](ClO4) (c).
Figure 24
Figure 24
Structure of the [Cu(phen)(L3)]Cl complex.
Figure 25
Figure 25
Structure of the [Cu(pabt)(phen)](ClO4) complex.
Figure 26
Figure 26
Structure of the [Cu2(μ-oda)(phen)4](ClO4)2 complex.
Figure 27
Figure 27
Structure of complexes [Cu(phen)(SCH)Cu(OAc)] (a) and [Cu2(SCH)(phen)2](OAc) (b).
Figure 28
Figure 28
Structure of the [Cu2(L4)(phen)](ClO4) complex.
Figure 29
Figure 29
The candidate cellular structures and molecular mechanisms interfering with copper-phen complexes visualized in the A-2780 cancer cell.
See this image and copyright information in PMC

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