Mechanism of alterations in isolated rat liver mitochondrial function induced by gold complexes of bidentate phosphines.

Hoke, Glenn D.; Rush, Glenn F.; Bossard, G F; McArdle, James V.; Jensen, Benny; Mirabelli, Christopher K.

doi:10.1016/s0021-9258(18)37942-0

Cited by 68 publications

(21 citation statements)

References 41 publications

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“…258 Some gold complexes have shown high biological activity, however the primary target of most of these compounds appears to be mitochondrial DNA. [259][260][261] Gold complexes (e.g. [Au(terpy)Cl]Cl 2 (45) and [Au( phen)Cl 2 ]Cl, Fig.…”

Section: Intercalationmentioning

confidence: 99%

Metal complex interactions with DNA

2015

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Increasing numbers of DNA structures are being revealed using biophysical, spectroscopic and genomic methods. The diversity of transition metal complexes is also growing, as the unique contributions that transition metals bring to the overall structure of metal complexes depend on the various coordination numbers, geometries, physiologically relevant redox potentials, as well as kinetic and thermodynamic characteristics. The vast range of ligands that can be utilised must also be considered. Given this diversity, a variety of biological interactions is not unexpected. Specifically, interactions with negatively-charged DNA can arise due to covalent/coordinate or subtle non-coordinate interactions such as electrostatic attraction, groove binding and intercalation as well as combinations of all of these modes. The potential of metal complexes as therapeutic agents is but one aspect of their utility. Complexes, both new and old, are currently being utilised in conjunction with spectroscopic and biological techniques to probe the interactions of DNA and its many structural forms. Here we present a review of metal complex-DNA interactions in which several binding modes and DNA structural forms are explored.

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Section: Intercalationmentioning

confidence: 99%

Metal complex interactions with DNA

2015

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“…33 However, the high lipophilicity of these compounds results in severe toxicity, a consequence of the non-selective concentration of compounds into mitochondria of both tumourigenic and non-tumourigenic cells, causing general membrane permeabilisation. 34,35 Despite the significant antitumour activity of [Au(dppe) 2 ]Cl against a range of tumour models in mice, 31 its clinical development was halted following preclinical toxicological studies in dogs and rabbits that identified severe toxicities to heart, liver and lung, as a result of mitochondrial dysfunction. [34][35][36][37] Replacing the phenyl substituents with pyridyl groups (with the N atom in either the 2, 3 or 4 position in the ring), provided a series of compounds of type [Au(dnpype) 2 ]Cl (Scheme 2) that are structurally similar to [Au(dppe) 2 ]Cl with hydrophiliclipophilic character spanning a very large range.…”

Section: Gold(i) Anticancer Compoundsmentioning

confidence: 99%

“…34,35 Despite the significant antitumour activity of [Au(dppe) 2 ]Cl against a range of tumour models in mice, 31 its clinical development was halted following preclinical toxicological studies in dogs and rabbits that identified severe toxicities to heart, liver and lung, as a result of mitochondrial dysfunction. [34][35][36][37] Replacing the phenyl substituents with pyridyl groups (with the N atom in either the 2, 3 or 4 position in the ring), provided a series of compounds of type [Au(dnpype) 2 ]Cl (Scheme 2) that are structurally similar to [Au(dppe) 2 ]Cl with hydrophiliclipophilic character spanning a very large range. 38,39 Studies carried out in isolated rat hepatocytes, and a panel of cisplatinresistant human ovarian carcinoma cell lines, showed a general increase in cytotoxic potency (and decrease in selectivity) with increasing lipophilicity.…”

Section: Gold(i) Anticancer Compoundsmentioning

confidence: 99%

Gold compounds as therapeutic agents for human diseases

2011

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The application of gold in medicine is traceable for several thousand years and Au(i) compounds have been used clinically to treat rheumatoid arthritis since the last century. Recently research into gold-based drugs for a range of human diseases has seen a renaissance. Old as well as new Au(i) and Au(iii) compounds have been used and designed with an aim of targeting cellular components that are implicated in the onset or progression of cancers, rheumatoid arthiritis, viral and parasitic diseases. In addition, new disease targets have been found for gold compounds that have given insight into the mechanism of action of these compounds, as well as in the molecular pathophysiology of human diseases. Here we discuss the rationale for the design and use of gold compounds that have specific and selective targets in cells to alleviate the symptoms of a range of human diseases. We summarise the most recent findings in this research and our own discoveries to show that gold compounds can be developed to become versatile and powerful drugs for diseases caused by dysfunction of selenol and thiol containing proteins.

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“…4) cationic complex [Au(dppe) 2 ] + (where dppe = 1,2-bis(diphenylphosphino)ethane) has shown mitochondrial targeting behaviour 41 and subsequent disruption of mitochondrial function. 42 Structurally related complexes with increasing hydrophilic character, achieved by replacing the phenyl substituents with pyridyl groups, have also been studied. A careful balance of the amphiphilic nature can modulate protein binding, excretion pathways and overall toxicity.…”

Section: Brief Comment On the Therapeutic Activity Of Au(i) Complexesmentioning

confidence: 99%

Recent developments in gold(i) coordination chemistry: luminescence properties and bioimaging opportunities

Langdon-Jones

Pope

2014

Chem. Commun.

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The fascinating biological activity of gold coordination compounds has led to the development of a wide range of complexes. The precise biological action of such species is often poorly understood and the ability to map gold distribution in cellular environments is key. This article discusses the recent progress in luminescent Au(I) complexes whilst considering their utility in bioimaging and therapeutics.

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Mechanism of alterations in isolated rat liver mitochondrial function induced by gold complexes of bidentate phosphines.

Cited by 68 publications

References 41 publications

Metal complex interactions with DNA

Metal complex interactions with DNA

Gold compounds as therapeutic agents for human diseases

Recent developments in gold(i) coordination chemistry: luminescence properties and bioimaging opportunities

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