Abstract
Metal-based drugs have been used in medicine for millennia, and some of them are still in use in current medicine. For example, in the treatment of diseases like cancer (Cisplatin) or rheumatoid arthritis (Auranofin), as well as used as antimicrobial agents (silver sulfadiazine) or radiopharmaceuticals. Some of the pharmacological properties of these metal compounds are due to their interactions with protein targets.
In this thesis, the potential of novel metal-based compounds as proteins/enzymes inhibitors is highlighted, which may infer them promising anticancer properties.
In Part A, gold(III) compounds are presented, which showed to potently inhibit the human membrane protein channels aquaglyceroporins (AQPs) and that can be used as chemical tools to understand the roles of AQPs in physiology and pathophysiology. The studies were conducted via different biophysical, biological and computational methods and unraveled the mechanisms of AQPs inhibition by gold compounds at a molecular level.
Additionally, in Part B, we present the study of different families of gold compounds as anticancer agents. Specifically, a new series of bifunctional fluorescent compounds (gold-ruthenium) showed promising anticancer effects in vitro and could be studied in cells via fluorescence microscopy. Moreover, an other series of organometallic gold(I) N-heterocyclic carbenes with a fluorescent coumarin moiety showed promising anticancer effects which are most likely due to the inhibition of the seleno-enzyme thioredoxin reductase (TrxR).
Overall, our results demonstrate that gold compounds have great potential for applications in chemical biology and medicine.
In this thesis, the potential of novel metal-based compounds as proteins/enzymes inhibitors is highlighted, which may infer them promising anticancer properties.
In Part A, gold(III) compounds are presented, which showed to potently inhibit the human membrane protein channels aquaglyceroporins (AQPs) and that can be used as chemical tools to understand the roles of AQPs in physiology and pathophysiology. The studies were conducted via different biophysical, biological and computational methods and unraveled the mechanisms of AQPs inhibition by gold compounds at a molecular level.
Additionally, in Part B, we present the study of different families of gold compounds as anticancer agents. Specifically, a new series of bifunctional fluorescent compounds (gold-ruthenium) showed promising anticancer effects in vitro and could be studied in cells via fluorescence microscopy. Moreover, an other series of organometallic gold(I) N-heterocyclic carbenes with a fluorescent coumarin moiety showed promising anticancer effects which are most likely due to the inhibition of the seleno-enzyme thioredoxin reductase (TrxR).
Overall, our results demonstrate that gold compounds have great potential for applications in chemical biology and medicine.
| Original language | English |
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| Qualification | Doctor of Philosophy |
| Awarding Institution |
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| Supervisors/Advisors |
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| Award date | 8-Apr-2016 |
| Place of Publication | [Groningen] |
| Publisher | |
| Print ISBNs | 978-90-367-8745-1 |
| Electronic ISBNs | 978-90-367-8744-4 |
| Publication status | Published - 2016 |