Recent progress in the development of organometallics for the treatment of cancer

Murray, Benjamin; Dyson, Paul J.

doi:10.1016/j.cbpa.2019.11.001

Cited by 79 publications

(53 citation statements)

References 46 publications

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“…[1] In recent years, research dedicated to the development of new pharmaceuticals has investigated a range of different complexes that contain metal centre atoms, such as Ag, Au, Ir, Pd, Os, Ru, Rh, Re and Ti. [2][3] In particular, Re-based complexes have recently drawn interest. Typically, Re has been associated with nuclear imaging applications due to the medical relevance of the isotope 99m Tc, which is used in approximately 90 % of all nuclear imaging applications.…”

Section: Introductionmentioning

confidence: 99%

Rhenium‐Based Complexes and in Vivo Testing: A Brief History

2020

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The success of metal‐based anticancer therapeutics in the treatment of cancer is best exemplified by cisplatin. Currently used in 32/78 cancer regimens, metal‐based drugs have a clear role in cancer therapy. Despite this, metal‐based anticancer therapeutics are not without drawbacks, with issues such as toxic side effects and the development of resistance mechanisms. This has led to investigations of other metal‐based drug candidates such as auranofin, a gold‐based drug candidate as well as ruthenium‐based candidates, NAMI‐A, NKP‐1339 and TLD‐1433. All are currently undergoing clinical trials. Another class of complexes under study are rhenium‐based; such complexes have undergone extensive in vitro testing but only nine have been reported to display antitumour in vivo activity, which is a necessary step before entering clinical trials. This review will document, chronologically, the rhenium‐based drug candidates that have undergone in vivo testing and the outlook for such complexes.

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Section: Introductionmentioning

confidence: 99%

Rhenium‐Based Complexes and in Vivo Testing: A Brief History

2020

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“…Half-sandwich organometallics are some of the most widely investigated compounds. Initially being led by Ru(arene) derivatives with their designable biological properties [ 6 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ], more and more isostructural Os analogues as well as Rh- and Ir(Cp*) derivatives with interesting properties have been reported [ 13 , 15 , 16 ]. The differences in properties can often be pinned down to varying ligand exchange kinetics, target site specificity and lipophilicity [ 13 , 17 , 18 , 19 , 20 , 21 , 22 ], which allow for more efficient interactions with biological target molecules, binding at specific target sites, and cell accumulation, respectively.…”

Section: Introductionmentioning

confidence: 99%

Thiourea-Derived Chelating Ligands and Their Organometallic Compounds: Investigations into Their Anticancer Activity

et al. 2020

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Thiones have been investigated as ligands in metal complexes with catalytic and biological activity. We report the synthesis, characterization, and biological evaluation of a series of MII/III complexes of the general formulae [MII(cym)(L)Cl]X (cym = η6-p-cymene) or [MIII(Cp*)(L)Cl]X (Cp* = η5-pentamethylcyclopentadienyl), where X = Cl− or PF6−, and L represents heterocyclic derivatives of thiourea. The thiones feature a benzyl-triazolyl pendant and they act as bidentate ligands via N,S-coordination to the metal centers. Several derivatives have been investigated by single-crystal X-ray diffraction analysis. NMR investigations showed a counterion-dependent shift of several protons due to the interaction with the counterions. These NMR investigations were complemented with X-ray diffraction analysis data and the effects of different counterions on the secondary coordination sphere were also investigated by DFT calculations. In biological studies, the Ir benzimidazole derivative was found to accumulate in the cytoplasm and it was the most cytotoxic derivative investigated.

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“…Indeed, transition metal complexes possess peculiar properties associated with the metal center, which are not available on organic compounds, and thus provide a superior medicinal potential [ 4 ]. In this regard, some categories of organometallic complexes have shown a great promise [ 5 ], and in particular piano-stool iridium(III) complexes of general formula [IrCp*(X^Y)Cl] 0/+ (Cp* = η 5 -C 5 Me 5 ; X^Y = bidentate neutral ligand or anionic 2-arylpyridyl ligand) have been intensively investigated ( Figure 1 , structure I ) [ 6 , 7 ]. Compounds of this type, as well as a variety of their derivatives (see below), are typically accessible from dinuclear precursors upon addition of the bidentate ligand (X^Y) via cleavage of chloride bridges.…”

Section: Introductionmentioning

confidence: 99%

A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η5-C5Me4R} Complexes with Variable R Groups

Palo

Drača

Murrali

et al. 2021

IJMS

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Piano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand (Cp*) have been intensively investigated as anticancer drug candidates and hold much promise in this setting. A systematic study aimed at outlining the effect of Cp* mono-derivatization on the antiproliferative activity is presented here. Thus, the dinuclear complexes [Ir(η5-C5Me4R)Cl(μ-Cl)]2 (R = Me, 1a; R = H, 1b; R = Pr, 1c; R = 4-C6H4F, 1d; R = 4-C6H4OH, 1e), their 2-phenylpyridyl mononuclear derivatives [Ir(η5-C5Me4R)(kN,kCPhPy)Cl] (2a–d), and the dimethylsulfoxide complex [Ir{η5-C5Me4(4-C6H4OH)}Cl2(κS-Me2S=O)] (3) were synthesized, structurally characterized, and assessed for their cytotoxicity towards a panel of six human and rodent cancer cell lines (mouse melanoma, B16; rat glioma, C6; breast adenocarcinoma, MCF-7; colorectal carcinoma, SW620 and HCT116; ovarian carcinoma, A2780) and one primary, human fetal lung fibroblast cell line (MRC5). Complexes 2b (R = H) and 2d (4-C6H4F) emerged as the most active ones and were selected for further investigation. They did not affect the viability of primary mouse peritoneal cells, and their tumoricidal action arises from the combined influence on cellular proliferation, apoptosis and senescence. The latter is triggered by mitochondrial failure and production of reactive oxygen and nitrogen species.

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Recent progress in the development of organometallics for the treatment of cancer

Cited by 79 publications

References 46 publications

Rhenium‐Based Complexes and in Vivo Testing: A Brief History

Rhenium‐Based Complexes and in Vivo Testing: A Brief History

Thiourea-Derived Chelating Ligands and Their Organometallic Compounds: Investigations into Their Anticancer Activity

A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η5-C5Me4R} Complexes with Variable R Groups

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