Antitumour action of rhodium (I) and iridium (I) complexes

Giraldi, Tullio; Sava, Gianni; Mestroni, G.; Zassinovich, G.; Stolfa, D.

doi:10.1016/0009-2797(78)90128-x

Cited by 51 publications

(23 citation statements)

References 9 publications

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“…Consequently, inefficient cellular drug uptake has to be considered as a possible reason together with kinetical inertness for low biological activity of many chloridoiridium species [3][4][5][6].…”

Section: Discussionmentioning

confidence: 99%

“…Together with the possibility that the iridium center might enable specific interactions with biological targets, which are not possible with "normal" organic drugs, these complexes fulfill the basic requirements to generate new innovative drugs. However, the inertness of iridium complexes may also be the reason for only a very limited number of available reports on the biological activity of iridium species [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Atomic absorption spectrometric determination of the iridium content in tumor cells exposed to an iridium metallodrug

Ott

Scharwitz

Scheffler

et al. 2008

Journal of Pharmaceutical and Biomedical Analysis

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Atomic absorption spectrometric determination of the iridium content in tumor cells exposed to an iridium metallodrug

Ott

Scharwitz

Scheffler

et al. 2008

Journal of Pharmaceutical and Biomedical Analysis

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“…Other antitumour rhodium(I) and iridium(I) compounds with in vivo activity were the organometallic, neutral and square planar rhodium(I) cyclo-octadiene complexes [Rh~CI(COD)(NH3)] and [RhICI(COD) -(piperidine)] (COD = cis, cis-l,5-cyclo-octadiene), which had antitumour activity against the Ehrlich ascites tumour (Giraldi et al 1974), and the acetylacetonato (acac) derivatives [RhI(acac)(COD)] and [Ir I-(acac)(COD)], which inhibited the growth of the leukemia L1210, sarcoma 180, and Ehrlich ascites carcinoma (Giraldi 1978) and had antitumour and, in the case of the rhodium-acac complex, also antimetastatic activity in the metastasizing Lewis lung carcinoma similar to that of cisplatin (Sava et al 1983). Some years later, the ionic and square planar Rh(I) complexes cyclo-octadiene(2-pyridinalmethylimine)rhodium chloride [Rh I-(COD)(NCsH4CH=NCH3]+ C1-and cyclo-octadiene-(2-pyridinalisopropylimine)rhodium chloride [Rh I-(COD)(NCsH4CH=N-i-C3H7)]+C1 -were shown to have similar activity and to prolong life in mice with the P388 leukemia and to have antineoplastic and antimetastatic effects in the Lewis lung and the MCa mammary carcinoma systems (Sava et al 1989b).…”

Section: Complexes Of Rhodium and Iridiummentioning

confidence: 99%

Complexes of metals other than platinum as antitumour agents

Köpf-Maier

1994

Eur J Clin Pharmacol

248

150

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The earliest reports on the therapeutic use of metals or metal-containing compounds in cancer and leukemia date from the sixteenth and nineteenth centuries. They were forgotten until the 1960s, when the anti-tumour activity of the inorganic complex cis-diammine-dichloroplatinum(II) (cisplatin) was discovered. This led to the development of other types of non-organic cytostatic drugs. Cisplatin has developed into one of the most frequently used and most effective cytostatic drugs for the treatment of solid carcinomas. Numerous other metal compounds containing platinum, other platinum metals, and even non-platinum metals were then shown to be effective against tumours in man and experimental tumours in animals. These compounds comprise main-group metallic compounds of gallium, germanium, tin, and bismuth, early-transition metal complexes of titanium, vanadium, niobium, molybdenum, and rhenium, and late-transition metal complexes of ruthenium, rhodium, iridium, platinum, copper, and gold. Several platnium complexes and four non-platnium-metal antitumour agents have so far entered early clinical trials. Gallium trinitrate and spirogermanium have already passed phase II clinical studies and have shown limited cytostatic activity against certain human carcinomas and lymphomas. The two early-transition metal complexes budotitane and titanocene dichloride have just reached the end of phase I clinical trials and have been found to have an unusual pattern of organ toxicity in man. Titanocene dichloride will soon enter phase II clinical studies.

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“…Iridium complexes were first investigated for their anticancer activity shortly after the discovery of cisplatin. Over the period 1970–2000, attention was focused on 5d 8 Ir I compounds with square-planar geometry similar to cisplatin, such as [Ir(acac)(cod)] ( 1 ) 18 and dinuclear [IrCl(cod)] 2 ( 2 ), 19 Figure 2. Encouragingly, 1 gave 100% cures in mice bearing Ehrlich ascites, and inhibited growth of subcutaneous Lewis lung carcinoma in mice.…”

Section: Introductionmentioning

confidence: 99%

Organoiridium Complexes: Anticancer Agents and Catalysts

2014

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ConspectusIridium is a relatively rare precious heavy metal, only slightly less dense than osmium. Researchers have long recognized the catalytic properties of square-planar IrI complexes, such as Crabtree’s hydrogenation catalyst, an organometallic complex with cyclooctadiene, phosphane, and pyridine ligands. More recently, chemists have developed half-sandwich pseudo-octahedral pentamethylcyclopentadienyl IrIII complexes containing diamine ligands that efficiently catalyze transfer hydrogenation reactions of ketones and aldehydes in water using H2 or formate as the hydrogen source. Although sometimes assumed to be chemically inert, the reactivity of low-spin 5d6 IrIII centers is highly dependent on the set of ligands. Cp* complexes with strong σ-donor C∧C-chelating ligands can even stabilize IrIV and catalyze the oxidation of water. In comparison with well developed Ir catalysts, Ir-based pharmaceuticals are still in their infancy. In this Account, we review recent developments in organoiridium complexes as both catalysts and anticancer agents.Initial studies of anticancer activity with organoiridium complexes focused on square-planar IrI complexes because of their structural and electronic similarity to PtII anticancer complexes such as cisplatin. Recently, researchers have studied half-sandwich IrIII anticancer complexes. These complexes with the formula [(Cpx)Ir(L∧L′)Z]0/n+ (with Cp* or extended Cp* and L∧L′ = chelated C∧N or N∧N ligands) have a much greater potency (nanomolar) toward a range of cancer cells (especially leukemia, colon cancer, breast cancer, prostate cancer, and melanoma) than cisplatin. Their mechanism of action may involve both an attack on DNA and a perturbation of the redox status of cells. Some of these complexes can form IrIII-hydride complexes using coenzyme NAD(P)H as a source of hydride to catalyze the generation of H2 or the reduction of quinones to semiquinones. Intriguingly, relatively unreactive organoiridium complexes containing an imine as a monodentate ligand have prooxidant activity, which appears to involve catalytic hydride transfer to oxygen and the generation of hydrogen peroxide in cells. In addition, researchers have designed inert IrIII complexes as potent kinase inhibitors. Octahedral cyclometalated IrIII complexes not only serve as cell imaging agents, but can also inhibit tumor necrosis factor α, promote DNA oxidation, generate singlet oxygen when photoactivated, and exhibit good anticancer activity. Although relatively unexplored, organoiridium chemistry offers unique features that researchers can exploit to generate novel diagnostic agents and drugs with new mechanisms of action.

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Antitumour action of rhodium (I) and iridium (I) complexes

Cited by 51 publications

References 9 publications

Atomic absorption spectrometric determination of the iridium content in tumor cells exposed to an iridium metallodrug

Atomic absorption spectrometric determination of the iridium content in tumor cells exposed to an iridium metallodrug

Complexes of metals other than platinum as antitumour agents

Organoiridium Complexes: Anticancer Agents and Catalysts

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