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Auteur Catherine Hemmert |
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Titre : Drug-containing NHC-Gold complexes for biomedical applications Type de document : texte imprimé Auteurs : Álvarez Álvaro Fernández, Auteur ; Catherine Hemmert, Directeur de thèse ; Heinz Gornitzka, Directeur de thèse Langues : Anglais (eng) Tags : MALARIA GOLD NHC ARTEMISININ TRICLOSAN Résumé : "Malaria is the most important parasitic infection in people, threatening around 40% of the human population. In the last years it has become a bigger public health concern because of the augmentation of malaria parasites resistant to artemisinin and its derivatives. Some NHC-gold(I) complexes show antimalarial activities, being a very promising alternative in malaria treatment because of their potential to inhibit thioredoxin reductase (TrxR) that plays a major role in mitochondrial respiratory chain (one of the two pathways that remains active in the quiescent state of the resistant parasites). In this work of thesis a panel of drug-NHC-gold(I) complexes including artemisinin and triclosan moieties has been synthesized and characterized with the objective of developing hybrid molecules with a dual mode of action able to overcome plasmodium resistance to artemisinin and its derivatives. The first group of molecules concerns a family of aliphatic or aromatic-functionalized cationic bis-NHC-gold(I) and neutral mono-NHC-gold(I) complexes with an artemisinin moiety connected through an aliphatic linker. The group includes three series depending on the length of the aliphatic linker (C3, C4, and C5). The three series have been tested against the sensible F32-TEM strain of P. falciparum showing high activities with IC50 values in the nM range. The second group concerns a series of aliphatic or aromatic-functionalized bis-NHC-gold(I) complexes with an triclosan moiety connected through an aliphatic linker. Triclosan inhibits the fatty acid synthesis pathway, which also remains active in the quiescent state on resistant parasites. These complexes were tested against P. falciparum showing, high activities with IC50 values in the nM range. The ligands of this series and their respective complexes have been also tested against one of the leishmaniosis causing parasites, L. infantum, being very effective in both, amastigote and promastigote forms, with IC50 values in the low µM range." Document : Thèse de Doctorat Etablissement_delivrance : Université de Toulouse 3 Date_soutenance : 28/09/2018 Ecole_doctorale : Sciences de la matière (SdM) Toulouse Domaine : Chimie, Biologie, Santé En ligne : http://thesesups.ups-tlse.fr/4056/ Drug-containing NHC-Gold complexes for biomedical applications [texte imprimé] / Álvarez Álvaro Fernández, Auteur ; Catherine Hemmert, Directeur de thèse ; Heinz Gornitzka, Directeur de thèse . - [s.d.].
Langues : Anglais (eng)
Tags : MALARIA GOLD NHC ARTEMISININ TRICLOSAN Résumé : "Malaria is the most important parasitic infection in people, threatening around 40% of the human population. In the last years it has become a bigger public health concern because of the augmentation of malaria parasites resistant to artemisinin and its derivatives. Some NHC-gold(I) complexes show antimalarial activities, being a very promising alternative in malaria treatment because of their potential to inhibit thioredoxin reductase (TrxR) that plays a major role in mitochondrial respiratory chain (one of the two pathways that remains active in the quiescent state of the resistant parasites). In this work of thesis a panel of drug-NHC-gold(I) complexes including artemisinin and triclosan moieties has been synthesized and characterized with the objective of developing hybrid molecules with a dual mode of action able to overcome plasmodium resistance to artemisinin and its derivatives. The first group of molecules concerns a family of aliphatic or aromatic-functionalized cationic bis-NHC-gold(I) and neutral mono-NHC-gold(I) complexes with an artemisinin moiety connected through an aliphatic linker. The group includes three series depending on the length of the aliphatic linker (C3, C4, and C5). The three series have been tested against the sensible F32-TEM strain of P. falciparum showing high activities with IC50 values in the nM range. The second group concerns a series of aliphatic or aromatic-functionalized bis-NHC-gold(I) complexes with an triclosan moiety connected through an aliphatic linker. Triclosan inhibits the fatty acid synthesis pathway, which also remains active in the quiescent state on resistant parasites. These complexes were tested against P. falciparum showing, high activities with IC50 values in the nM range. The ligands of this series and their respective complexes have been also tested against one of the leishmaniosis causing parasites, L. infantum, being very effective in both, amastigote and promastigote forms, with IC50 values in the low µM range." Document : Thèse de Doctorat Etablissement_delivrance : Université de Toulouse 3 Date_soutenance : 28/09/2018 Ecole_doctorale : Sciences de la matière (SdM) Toulouse Domaine : Chimie, Biologie, Santé En ligne : http://thesesups.ups-tlse.fr/4056/ Metal-NHC complexes for anti-cancer applications : gold(I) for antimitochondrial activity and iridium(III) for photodynamic therapy / Chen Zhang
Titre : Metal-NHC complexes for anti-cancer applications : gold(I) for antimitochondrial activity and iridium(III) for photodynamic therapy Type de document : texte imprimé Auteurs : Chen Zhang, Auteur ; Heinz Gornitzka, Directeur de thèse ; Catherine Hemmert, Directeur de thèse Langues : Anglais (eng) Tags : GOLD(I) NHC ANTICANCER PHOTODYNAMIC THERAPY LIPOPHILICITY Résumé : "In this work of thesis, several groups of novel NHC-based gold(I) complexes containing aliphatic and aromatic amino-side arms with interesting potential in biomedical applications have been synthesized and fully characterized. Also, a series of iridium(III) complexes containing NHC ligands with pronounced PDT anticancer activities has been prepared and fully characterized. The first group represents a family of cationic bis(NHC)-gold(I) complexes containing aliphatic amino-side arms. These complexes have been synthesized and investigated for their antiproliferative activities towards four human cancer cell lines and the non-cancerous MDCK cell line. In this series, the lipophilicity correlates directly with the cytotoxic activity against cancer cells. The second family of compounds concerns cationic gold(I) bis(NHC) complexes containing aromatic amino-side arms. The in vitro cytotoxicity of these complexes and proligands on the representative PC-3 prostate and T24 bladder cancer cell lines has been evaluated. All these complexes show higher Log P values (lipophilicity) than the first series of complexes, and in line with this higher cytotoxicity, nevertheless too high lipophilicity can also lead to lower selectivity. In order to develop a drug candidate with optimized activity and selectivity, we designed and synthesized the third family of cationic gold(I) bis(NHC) complexes. The Log P values of this series were between the first series and the second series. The lower cytotoxicity towards non-cancerous NIH3T3 cells was found for this series of complexes whereas they also displayed less activities towards cancer cells than the second series. The mechanistic studies on two gold complexes by monitoring the cellular uptake showed the rapid cellular accumulation of the intact gold bis(NHC) and a good bioavailability, in good agreement with the antiproliferative activity of these two complexes. Moreover, both complexes inhibit TrxR, a common target for gold(I) complexes. The cell death induced by these two complexes was ROS-dependent. Besides anticancer activities, we also tested gold(I) mono-NHC complexes for other biomedical applications in parasite disease Leishmaniasis. They were screened in vitro against both promastigote and axenic amastigote forms of L. infantum. Moreover, their cytotoxicity was evaluated on the murine J774A.1 macrophages in order to determine their selectivity of action. Another topic of this thesis concerns iridium(III)-NHC complexes. Three families of theranostic iridium(III)-NHC complexes were prepared and characterized. The in vitro cytotoxicity of all the complexes against PC-3 prostate, T24 bladder cancer cells and non-cancerous NIH3T3 cells was evaluated. Moreover, all complexes are theranostic agents, and the confocal microscopy experiments of one complex showed that it can be quickly and effectively taken up into PC-3 cells and specifically localize into mitochondria. Interestingly, these complexes can act as efficient photosensitizers. The cytotoxicity of these complexes was increased substantially upon 365 nm light irradiation, which suggested the high potential to be mitochondria-targeting theranostic anticancer agents for photodynamic therapy." Document : thèse de Doctorat Etablissement_delivrance : Université de Toulouse 3 Date_soutenance : 26/09/2018 Ecole_doctorale : Sciences de la Matière (SdM) (Toulouse) Domaine : Chimie Organométallique et de Coordination En ligne : https://theses.hal.science/tel-02146373 Metal-NHC complexes for anti-cancer applications : gold(I) for antimitochondrial activity and iridium(III) for photodynamic therapy [texte imprimé] / Chen Zhang, Auteur ; Heinz Gornitzka, Directeur de thèse ; Catherine Hemmert, Directeur de thèse . - [s.d.].
Langues : Anglais (eng)
Tags : GOLD(I) NHC ANTICANCER PHOTODYNAMIC THERAPY LIPOPHILICITY Résumé : "In this work of thesis, several groups of novel NHC-based gold(I) complexes containing aliphatic and aromatic amino-side arms with interesting potential in biomedical applications have been synthesized and fully characterized. Also, a series of iridium(III) complexes containing NHC ligands with pronounced PDT anticancer activities has been prepared and fully characterized. The first group represents a family of cationic bis(NHC)-gold(I) complexes containing aliphatic amino-side arms. These complexes have been synthesized and investigated for their antiproliferative activities towards four human cancer cell lines and the non-cancerous MDCK cell line. In this series, the lipophilicity correlates directly with the cytotoxic activity against cancer cells. The second family of compounds concerns cationic gold(I) bis(NHC) complexes containing aromatic amino-side arms. The in vitro cytotoxicity of these complexes and proligands on the representative PC-3 prostate and T24 bladder cancer cell lines has been evaluated. All these complexes show higher Log P values (lipophilicity) than the first series of complexes, and in line with this higher cytotoxicity, nevertheless too high lipophilicity can also lead to lower selectivity. In order to develop a drug candidate with optimized activity and selectivity, we designed and synthesized the third family of cationic gold(I) bis(NHC) complexes. The Log P values of this series were between the first series and the second series. The lower cytotoxicity towards non-cancerous NIH3T3 cells was found for this series of complexes whereas they also displayed less activities towards cancer cells than the second series. The mechanistic studies on two gold complexes by monitoring the cellular uptake showed the rapid cellular accumulation of the intact gold bis(NHC) and a good bioavailability, in good agreement with the antiproliferative activity of these two complexes. Moreover, both complexes inhibit TrxR, a common target for gold(I) complexes. The cell death induced by these two complexes was ROS-dependent. Besides anticancer activities, we also tested gold(I) mono-NHC complexes for other biomedical applications in parasite disease Leishmaniasis. They were screened in vitro against both promastigote and axenic amastigote forms of L. infantum. Moreover, their cytotoxicity was evaluated on the murine J774A.1 macrophages in order to determine their selectivity of action. Another topic of this thesis concerns iridium(III)-NHC complexes. Three families of theranostic iridium(III)-NHC complexes were prepared and characterized. The in vitro cytotoxicity of all the complexes against PC-3 prostate, T24 bladder cancer cells and non-cancerous NIH3T3 cells was evaluated. Moreover, all complexes are theranostic agents, and the confocal microscopy experiments of one complex showed that it can be quickly and effectively taken up into PC-3 cells and specifically localize into mitochondria. Interestingly, these complexes can act as efficient photosensitizers. The cytotoxicity of these complexes was increased substantially upon 365 nm light irradiation, which suggested the high potential to be mitochondria-targeting theranostic anticancer agents for photodynamic therapy." Document : thèse de Doctorat Etablissement_delivrance : Université de Toulouse 3 Date_soutenance : 26/09/2018 Ecole_doctorale : Sciences de la Matière (SdM) (Toulouse) Domaine : Chimie Organométallique et de Coordination En ligne : https://theses.hal.science/tel-02146373
Titre : Synthèse et caractérisations physico-chimiques de complexes métalliques comportant des ligands multidentes bis(carbène N-hétérocyclique) fonctionalisés : évaluation catalytique en couplage de Suzuki-Miyaura Type de document : texte imprimé Auteurs : François Jean-Baptiste dit Dominique, Auteur ; Catherine Hemmert, Directeur de thèse Langues : Français (fre) Tags : SEL D'IMIDAZOLIUM - CARBENES N-HETEROCYCLIQUES - COMPLEXES D’AGI, AUI, AUIII, PDII ET NIII - STRUCTURE RX - ELECTROCHIMIE - LUMINESCENCE - COUPLAGE DE SUZUKI-MIYAURA Résumé : "La découverte de complexes métalliques de carbènes N-hétérocycliques (CNH) et de CNHs stables et isolables, a soulevé un intérêt grandissant en chimie de coordination et en catalyse. Pour notre part, nous avons développé de nouveaux ligands bis-CNH fonctionalisés (amide ou alcool) multidentes. Les proligands (sels de bis(imidazolium) à pont flexible ou rigide) sont obtenus par des voies synthétiques courtes et modulables. Des complexes d'AuI, PdII et NiII ont été obtenus, par transmétallation de précurseurs d'AgI, ou par complexation directe des proligands en présence d'une base. L'oxydation chimique des complexes d'AuI a conduit aux complexes d'AuIII. Les complexes d'AuI et NiII ont été structuralement caractérisés par diffraction des RX et les propriétés électrochimiques et photophysiques des complexes d'AuI et d'AuIII ont été étudiées. Enfin, les complexes de NiII et PdII ont été évalués en réaction de couplage de Suzuki-Miyaura, montrant une activité modérée." Document : Thèse De Doctorat Etablissement_delivrance : Université Toulouse 3 Date_soutenance : 04/10/2008 Ecole_doctorale : Sciences de la matière (SdM) (Toulouse) Domaine : Chimie organométallique et de coordination En ligne : http://thesesups.ups-tlse.fr/347/ Synthèse et caractérisations physico-chimiques de complexes métalliques comportant des ligands multidentes bis(carbène N-hétérocyclique) fonctionalisés : évaluation catalytique en couplage de Suzuki-Miyaura [texte imprimé] / François Jean-Baptiste dit Dominique, Auteur ; Catherine Hemmert, Directeur de thèse . - [s.d.].
Langues : Français (fre)
Tags : SEL D'IMIDAZOLIUM - CARBENES N-HETEROCYCLIQUES - COMPLEXES D’AGI, AUI, AUIII, PDII ET NIII - STRUCTURE RX - ELECTROCHIMIE - LUMINESCENCE - COUPLAGE DE SUZUKI-MIYAURA Résumé : "La découverte de complexes métalliques de carbènes N-hétérocycliques (CNH) et de CNHs stables et isolables, a soulevé un intérêt grandissant en chimie de coordination et en catalyse. Pour notre part, nous avons développé de nouveaux ligands bis-CNH fonctionalisés (amide ou alcool) multidentes. Les proligands (sels de bis(imidazolium) à pont flexible ou rigide) sont obtenus par des voies synthétiques courtes et modulables. Des complexes d'AuI, PdII et NiII ont été obtenus, par transmétallation de précurseurs d'AgI, ou par complexation directe des proligands en présence d'une base. L'oxydation chimique des complexes d'AuI a conduit aux complexes d'AuIII. Les complexes d'AuI et NiII ont été structuralement caractérisés par diffraction des RX et les propriétés électrochimiques et photophysiques des complexes d'AuI et d'AuIII ont été étudiées. Enfin, les complexes de NiII et PdII ont été évalués en réaction de couplage de Suzuki-Miyaura, montrant une activité modérée." Document : Thèse De Doctorat Etablissement_delivrance : Université Toulouse 3 Date_soutenance : 04/10/2008 Ecole_doctorale : Sciences de la matière (SdM) (Toulouse) Domaine : Chimie organométallique et de coordination En ligne : http://thesesups.ups-tlse.fr/347/
Titre : Nouveaux complexes de bases de Schiff chirales macrocycliques de manganèse pour l'époxydation asymétrique d'oléfines Type de document : texte imprimé Auteurs : Martinez, Alexandre ; Bernard Meunier, Directeur de thèse ; Catherine Hemmert, Directeur de thèse ; Remi Chauvin, Directeur de thèse Année de publication : 2004 Langues : Français (fre) Document : Thèse de doctorat Etablissement_delivrance : Université de Toulouse Date_soutenance : 23/09/2004 Localisation : LCC Nouveaux complexes de bases de Schiff chirales macrocycliques de manganèse pour l'époxydation asymétrique d'oléfines [texte imprimé] / Martinez, Alexandre ; Bernard Meunier, Directeur de thèse ; Catherine Hemmert, Directeur de thèse ; Remi Chauvin, Directeur de thèse . - 2004.
Langues : Français (fre)
Document : Thèse de doctorat Etablissement_delivrance : Université de Toulouse Date_soutenance : 23/09/2004 Localisation : LCC
Titre : Synthesis of N-heterocyclic carbene gold(I) complexes: Towards the development of new organometallic drugs Type de document : texte imprimé Auteurs : Luca Boselli, Auteur ; Heinz Gornitzka, Directeur de thèse ; Catherine Hemmert, Directeur de thèse Année de publication : 2014 Langues : Anglais (eng) Tags : METALLODRUG ANTICANCER GOLD COMPLEX CARBENE COMPLEX Résumé : "Biomedical applications of gold complexes based on N-heterocyclic carbenes (NHCs) are beginning to unfold. Some cationic gold(I) NHCs complexes show antimitochondrial activities, a very promising action mode in the fight against cancer; due to their positive charge these complexes target preferentially tumor cells, leading to cell death.
In this work of thesis, three groups of new NHC-based gold and heterobimetallic complexes involving aliphatic or aromatic amino-functionalized NHCs with interesting potential in biomedical research have been synthetized and characterized.
The first group is formed by three luminescent heterobimetallic gold(I)-ruthenium(II) complexes containing heteroditopic bipyridine-NHC ligands. These compounds have been biologically investigated by in vitro tests for their antitumoral, antileishmanial and antimalarial activities. Finally, imaging studies in cancer cells have been performed exploiting the luminescent properties of the most active compound.
The second group of molecules is concerned by cationic gold(I) complexes containing two 1[2-(diethylamino)ethyl]imidazolydene ligands. First the complexes have been tested for their antiproliferative activity in prostate cancer cell line PC-3. Lipophilicity (Log P) has been determined for these complexes. The most active complex has been tested for the cytotoxic activities in five human cancer cell lines and primary endothelial cells demonstrating a potent action and selectivity for cancer cells. In addition, antileishmanial and antimalarial activities of these compounds have been investigated showing interesting results.
The third group is formed by a hetero-dinuclear gold(I)-silver(I) and a trinuclear gold(I)-copper(II) complexes containing phenanthroline-NHC ligands. The compounds are formed by two different organometallic units potentially able to act as multi-targeting anticancer drug."Document : Thèse de doctorat Etablissement_delivrance : Université de Toulouse 3 Date_soutenance : 04/12/2014 Ecole_doctorale : Science de la matière (université Toulouse III P. Sabatier) Domaine : Chimie organométallique de coordination Localisation : LCC En ligne : http://thesesups.ups-tlse.fr/2579/ Synthesis of N-heterocyclic carbene gold(I) complexes: Towards the development of new organometallic drugs [texte imprimé] / Luca Boselli, Auteur ; Heinz Gornitzka, Directeur de thèse ; Catherine Hemmert, Directeur de thèse . - 2014.
Langues : Anglais (eng)
Tags : METALLODRUG ANTICANCER GOLD COMPLEX CARBENE COMPLEX Résumé : "Biomedical applications of gold complexes based on N-heterocyclic carbenes (NHCs) are beginning to unfold. Some cationic gold(I) NHCs complexes show antimitochondrial activities, a very promising action mode in the fight against cancer; due to their positive charge these complexes target preferentially tumor cells, leading to cell death.
In this work of thesis, three groups of new NHC-based gold and heterobimetallic complexes involving aliphatic or aromatic amino-functionalized NHCs with interesting potential in biomedical research have been synthetized and characterized.
The first group is formed by three luminescent heterobimetallic gold(I)-ruthenium(II) complexes containing heteroditopic bipyridine-NHC ligands. These compounds have been biologically investigated by in vitro tests for their antitumoral, antileishmanial and antimalarial activities. Finally, imaging studies in cancer cells have been performed exploiting the luminescent properties of the most active compound.
The second group of molecules is concerned by cationic gold(I) complexes containing two 1[2-(diethylamino)ethyl]imidazolydene ligands. First the complexes have been tested for their antiproliferative activity in prostate cancer cell line PC-3. Lipophilicity (Log P) has been determined for these complexes. The most active complex has been tested for the cytotoxic activities in five human cancer cell lines and primary endothelial cells demonstrating a potent action and selectivity for cancer cells. In addition, antileishmanial and antimalarial activities of these compounds have been investigated showing interesting results.
The third group is formed by a hetero-dinuclear gold(I)-silver(I) and a trinuclear gold(I)-copper(II) complexes containing phenanthroline-NHC ligands. The compounds are formed by two different organometallic units potentially able to act as multi-targeting anticancer drug."Document : Thèse de doctorat Etablissement_delivrance : Université de Toulouse 3 Date_soutenance : 04/12/2014 Ecole_doctorale : Science de la matière (université Toulouse III P. Sabatier) Domaine : Chimie organométallique de coordination Localisation : LCC En ligne : http://thesesups.ups-tlse.fr/2579/
