Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jul 3;25(13):7314.
doi: 10.3390/ijms25137314.

Anticancer Activity of Metallodrugs and Metallizing Host Defense Peptides-Current Developments in Structure-Activity Relationship

Celia María Curieses Andrés  1 , José Manuel Pérez de la Lastra  2 , Elena Bustamante Munguira  1 , Celia Andrés Juan  3 , Eduardo Pérez-Lebeña  4
Affiliations
Review

Anticancer Activity of Metallodrugs and Metallizing Host Defense Peptides-Current Developments in Structure-Activity Relationship

Celia María Curieses Andrés et al. Int J Mol Sci. .

Abstract

This article provides an overview of the development, structure and activity of various metal complexes with anti-cancer activity. Chemical researchers continue to work on the development and synthesis of new molecules that could act as anti-tumor drugs to achieve more favorable therapies. It is therefore important to have information about the various chemotherapeutic substances and their mode of action. This review focuses on metallodrugs that contain a metal as a key structural fragment, with cisplatin paving the way for their chemotherapeutic application. The text also looks at ruthenium complexes, including the therapeutic applications of phosphorescent ruthenium(II) complexes, emphasizing their dual role in therapy and diagnostics. In addition, the antitumor activities of titanium and gold derivatives, their side effects, and ongoing research to improve their efficacy and reduce adverse effects are discussed. Metallization of host defense peptides (HDPs) with various metal ions is also highlighted as a strategy that significantly enhances their anticancer activity by broadening their mechanisms of action.

Keywords: cancer; cisplatin; metallodrugs; photodynamic and photoactivated therapy; ruthenium; structure-activity relationship.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Requirements for new metal compounds with antitumor activity.
Figure 2
Figure 2
Synthesis of cisplatin by the Dhara method.
Figure 3
Figure 3
Most relevant adverse effects.
Figure 4
Figure 4
Reaction between DNA and cisplatin.
Figure 5
Figure 5
Zinc-finger protein transcription factor coordinated to Zn left and Disrupted conformation of Zn-finger protein transcriptión factor (right figure).
Figure 6
Figure 6
Summary mechanisms of resistance to cisplatin.
Figure 7
Figure 7
Advances in the field of platinum complexes chronologically ordered, from the discovery of cisplatin to the present.
Figure 8
Figure 8
Pt(II) complexes approved worldwide ((right) figure) and in some countries ((left) figure). All of them have a square-planar geometry, with a coordination index of 4 for Pt.
Figure 9
Figure 9
Design of new platinum drugs.
Figure 10
Figure 10
(A) Trans-[PtCl2L2] complexes where L are aromatic amines; (B) trans-[PtCl2L2] complexes where L are iminoethers; (C) trans-[PtCl2L2] complexes where L are aliphatic amines and (D) trans-[PtCl2(triphenylphosphine)(aliphatic amine)] complexes.
Figure 11
Figure 11
Chemical structures of di and trinuclear Platinum agents.
Figure 12
Figure 12
Structures of some examples of anticancer Pt(IV) complexes.
Figure 13
Figure 13
Formation and activation of Pt(IV) prodrugs.
Figure 14
Figure 14
Formation of Pt(IV) prodrugs with various bioactive ligands.
Figure 15
Figure 15
Structure of Pt(IV) prodrugs based on valproic acid.
Figure 16
Figure 16
Structures of Pt(IV) prodrugs with 4-phenylbutyric acid ligands.
Figure 17
Figure 17
Structure of Pt(IV) prodrugs based on suberoyl-bis-hydroxamic acid.
Figure 18
Figure 18
Chalcoplatinum structure.
Figure 19
Figure 19
Ethacraplatin reduction.
Figure 20
Figure 20
Chemical structure of mitaplatin.
Figure 21
Figure 21
Chemical structure of Pt(IV) complex containing vitamin E derivatives.
Figure 22
Figure 22
Beneficial effects of using plant extracts together with cisplatin.
Figure 23
Figure 23
Chemical structure of salvianolic acid A and Epicatechin gallate.
Figure 24
Figure 24
Chemical structure of carnosic acid.
Figure 25
Figure 25
Computational prediction of the binding sites of Zn2+ (residue highlighted in red) to the HDP Chrysophsin-1 from Pagrus major (Red seabream) using IonCom server (https://zhanggroup.org/IonCom/ioncomsubmit.cgi), accessed on 5 June 2024. Peptide structure was visualized using ChimeraX (version 1.6.1).
Figure 26
Figure 26
Chemical structure of cisplatin and metallocene dichloride.
Figure 27
Figure 27
Hydrolysis of the titanocene dichloride complex.
Figure 28
Figure 28
Chemical structure of bis-[(p-methoxybenzyl)cyclopentadienyl]titanium dichloride (Titanocene Y).
Figure 29
Figure 29
Chemical structure of [cis-diethoxybis(1-phenylbutane-1,3-dionato) titanium (IV)] (Budotitane).
Figure 30
Figure 30
Structure of some anticancer Ru(III) complexes.
Figure 31
Figure 31
Typical generic structure of a piano stool compound with three monodentate ligands.
Figure 32
Figure 32
RAPTA complexes.
Figure 33
Figure 33
RAPTA family of anticancer agents.
Figure 34
Figure 34
Examples of Ru(II) polypyridyl complexes with antitumor activity.
Figure 35
Figure 35
(A) Octahedral Ru(II) complexes containing ON ligands, (B) coordinated OO and RDC34 with a cyclometalated ligand.
Figure 36
Figure 36
Molecular structure of the PS complex of Ru(II) TLD4133. Activation of the TLD-1433 complex.
Figure 37
Figure 37
Ru(II) polypyridyl PS complexes for PDT. (A) Ru(II) polypyridyl complex containing a triphenylphosphonium substituent. (B) 2,2’-bipyridine type complex with trans-stilbene groups in the 4’ and 4‘ positions of the pyridines. (C) Cyclometalated Ru(II) complex for PDT.
Figure 38
Figure 38
Ru(II) complexes for PDT containing monodentate ligands enzyme inhibitors. Left complex synthesized by Renfrew and right by Glazer.
Figure 39
Figure 39
Ru(II) complex with a monodentate ligand coordinated through a sulfur atom.
Figure 40
Figure 40
Auranofin [(tetra-O-acetyl-β-D-glucopyranosyl)-thio] (triethylphosphine)-Au(I).
Figure 41
Figure 41
(A) Linear Au(I) complexes similar to auranofin. (B) Au(I) complexes with phosphines derived from 1,3,5-triaza-7-phosphaadamantane.
Figure 42
Figure 42
(A) Structures of mononuclear and (B) dinuclear complexes with diphosphines.
Figure 43
Figure 43
Au(I) complexes with donor sulfur ligands.
Figure 44
Figure 44
Au(I) complexes with carbenes derived from 1,3-disubstituted imidazole.
Figure 45
Figure 45
First Au(I) derivatives with alkynyl ligands for the treatment of colon cancer.
Figure 46
Figure 46
Au(I) complex with a porphyrin-derived phosphine ligand.
Figure 47
Figure 47
Dinuclear Au(III) complex (left image) and porphyrin Au(III) complex (right image) designed by Che et al. [240].
Figure 48
Figure 48
Ti-Au heterometallic complex.
See this image and copyright information in PMC

References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Debela D.T., Muzazu S.G., Heraro K.D., Ndalama M.T., Mesele B.W., Haile D.C., Kitui S.K., Manyazewal T. New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Med. 2021;9:20503121211034366. doi: 10.1177/20503121211034366. - DOI - PMC - PubMed
    1. Rosenberg B. Some biological effects of platinum compounds. Platin. Met. Rev. 1971;15:42–51. doi: 10.1595/003214071X1524251. - DOI
    1. Bratsos I., Jedner S., Gianferrara T., Alessio E. Ruthenium anticancer compounds: Challenges and expectations. Chimia. 2007;61:692–697. doi: 10.2533/chimia.2007.692. - DOI
    1. Abu-Surrah A.S., Kettunen M. Platinum group antitumor chemistry: Design and development of new anticancer drugs complementary to cisplatin. Curr. Med. Chem. 2006;13:1337–1357. doi: 10.2174/092986706776872970. - DOI - PubMed

MeSH terms

LinkOut - more resources