Metal Complexes and Medicine: A Successful Combination

Gasser, Gilles

doi:10.2533/chimia.2015.442

Cited by 56 publications

(36 citation statements)

References 29 publications

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“…These results showed that Mo-cluster has some specificity of action and supports the further investigation of this cluster for their potential as new antiviral compounds. Similar compounds have previously shown potential for antiviral [24], antibacterial [42], and antiparasitic [12] activity, increasing the potential application of molybdenum clusters in different areas of infectious disease research.…”

Section: Resultsmentioning

confidence: 89%

“…Thus, the chemistry of the hexamolybdenum halide clusters is particularly attractive due to their synthetic versatility, thermal stability, luminescence, and redox properties [6,7,8,9,10]. The molybdenum hexanuclear type [M 6 X 8 Y 6 ] cluster and their derivatives have attracted increasing attention due to recent potential pharmacological applications [11,12]. Changes in their structure have offered a high degree of diversity that has proven useful for the development of new medicinal agents their improved potency and lesser toxicity [6,11], effects on in a wide range of cell types, in vitro, [13] and varying ligands, resulting in multiple components with diverse photophysical and redox properties [7].…”

Section: Introductionmentioning

confidence: 99%

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The [Mo6Cl14]2− Cluster is Biologically Secure and Has Anti-Rotavirus Activity In Vitro

et al. 2017

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The molybdenum cluster [Mo6Cl14]2− is a fluorescent component with potential for use in cell labelling and pharmacology. Biological safety and antiviral properties of the cluster are as yet unknown. Here, we show the effect of acute exposition of human cells and red blood cells to the molybdenum cluster and its interaction with proteins and antiviral activity in vitro. We measured cell viability of HepG2 and EA.hy926 cell lines exposed to increasing concentrations of the cluster (0.1 to 250 µM), by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Hemolysis and morphological alterations of red blood cells, obtained from healthy donors, exposed to the cluster (10 to 200 µM) at 37 °C were analyzed. Furthermore, quenching of tryptophan residues of albumin was performed. Finally, plaque formation by rotavirus SA11 in MA104 cells treated with the cluster (100 to 300 µM) were analyzed. We found that all doses of the cluster showed similar cell viability, hemolysis, and morphology values, compared to control. Quenching of tryptophan residues of albumin suggests a protein-cluster complex formation. Finally, the cluster showed antiviral activity at 300 µM. These results indicate that the cluster [Mo6Cl14]2− could be intravenously administered in animals at therapeutic doses for further in vivo studies and might be studied as an antiviral agent.

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Section: Resultsmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

The [Mo6Cl14]2− Cluster is Biologically Secure and Has Anti-Rotavirus Activity In Vitro

et al. 2017

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“…However, metal-based coordination complexes have played a crucial role in medicine throughout history, including the use of arsenic for the rst effective treatment of syphilis (Salvarsan), mercury in the topical antiseptic mercurochrome or the vaccine preservative thiomersal, and gold in the treatment of rheumatoid arthritis (Auranon). 7,8 Metal complexes became a cornerstone of medicinal chemistry with the approval of the chemotherapeutic platinum-based drug Cisplatin (1978), which is still used in a majority of all cancer treatments today. 9 In the last two decades, several more titanium-, iron-, ruthenium-, gallium-, palladium-, silver-, gold-, bismuth-, and copper-based metal complexes have reached human clinical trials as treatments for cancer, malaria and neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Metal Complexes as a Promising Source for New Antibiotics

Frei

Zuegg²,

Elliott³

et al. 2019

Preprint

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There is a dire need for new classes of antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug pipeline, consisting mostly of derivatives of known antibiotics, new classes of antibiotics are urgently required. Antibiotic compounds are notorious for not having very “drug-like” chemical structures. Metal complexes are currently in clinical development for the treatment of cancer, malaria and neurodegenerative diseases. However, only little attention has been paid to their application as potential antimicrobial compounds. We report the evaluation of 906 metal-containing compounds that have been screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial activity. Metal-bearing compounds display a significantly higher hit-rate (9.9%) when compared to the purely organic molecules (0.87%) in the CO-ADD database. Out of 906 compounds, 88 show activity against at least one of the tested strains, including fungi, while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties. Herein, we highlight the structures of the 30 compounds with activity against Gram-positive and/or Gram-negative bacteria containing Mn, Co, Zn, Ru, Ag, Eu, Ir and Pt, with activities down to the nanomolar range against methicillin resistant <i>S. aureus </i>(MRSA). This work reveals the vast diversity that metal-containing compounds can bring to antimicrobial research. It is important to raise awareness of these types of compounds for the design of truly novel antibiotics with potential for combatting antimicrobial resistance.

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“…In parallel, bioorganometallic chemistry provides new tools to influence biological interactions . Among a variety of organometallic compounds, transition‐metal carbonyls forged their presence in medicinal chemistry .…”

Section: Introductionmentioning

confidence: 99%

Organometallic Nucleosides: Synthesis and Biological Evaluation of Substituted Dicobalt Hexacarbonyl 2′‐Deoxy‐5‐oxopropynyluridines

et al. 2018

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Reactions of dicobalt octacarbonyl [Co2(CO)8] with 2′‐deoxy‐5‐oxopropynyluridines and related compounds gave dicobalt hexacarbonyl nucleoside complexes (83–31 %). The synthetic outcomes were confirmed by X‐ray structure determination of dicobalt hexacarbonyl 2′‐deoxy‐5‐(4‐hydroxybut‐1‐yn‐1‐yl)uridine, which exhibits intermolecular hydrogen bonding between a modified base and ribose. The electronic structure of this compound was characterized by the DFT calculations. The growth inhibition of HeLa and K562 cancer cell lines by organometallic nucleosides was examined and compared to that by alkynyl nucleoside precursors. Coordination of the dicobalt carbonyl moiety to the 2′‐deoxy‐5‐alkynyluridines led to a significant increase in the cytotoxic potency. The cobalt compounds displayed antiproliferative activities with median inhibitory values (IC50) in the range of 20 to 80 μm for the HeLa cell line and 18 to 30 μm for the K562 cell line. Coordination of an acetyl‐substituted cobalt nucleoside was expanded by using the 1,1‐bis(diphenylphosphino)methane (dppm) ligand, which exhibited cytotoxicity at comparable levels. The formation of reactive oxygen species in the presence of cobalt compounds was determined in K562 cells. The results indicate that the mechanism of action for most antiproliferative cobalt compounds may be related to the induction of oxidative stress.

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Metal Complexes and Medicine: A Successful Combination

Cited by 56 publications

References 29 publications

The [Mo6Cl14]2− Cluster is Biologically Secure and Has Anti-Rotavirus Activity In Vitro

The [Mo6Cl14]2− Cluster is Biologically Secure and Has Anti-Rotavirus Activity In Vitro

Metal Complexes as a Promising Source for New Antibiotics

Organometallic Nucleosides: Synthesis and Biological Evaluation of Substituted Dicobalt Hexacarbonyl 2′‐Deoxy‐5‐oxopropynyluridines

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