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Metallo-Drugs As Nitric Oxide

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Metallo-Drugs As Nitric Oxide Metallo-drugs as nitric oxide (NO•) and/or nitroxyl(HNO) donors : development of new agents and investigation of anticancer, antihypertensive and antituberculosis activities Edinilton Muniz Carvalho To cite this version: Edinilton Muniz Carvalho. Metallo-drugs as nitric oxide (NO•) and/or nitroxyl(HNO) donors : devel- opment of new agents and investigation of anticancer, antihypertensive and antituberculosis activities. Organic chemistry. Université Paul Sabatier - Toulouse III, 2020. English. NNT : 2020TOU30217. tel-03208714 HAL Id: tel-03208714 https://tel.archives-ouvertes.fr/tel-03208714 Submitted on 26 Apr 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE En vue de l’obtention du DOCTORAT DE L’UNIVERSITÉ DE TOULOUSE Délivré par Université Toulouse 3 Paul Sabatier (UT3 Paul Sabatier) Présentée et soutenue par Edinilton Muniz Carvalho Le 24 Novembre 2020 Titre : Metallo-drugs as nitric oxide (NO•) and/or nitroxyl (HNO) donors: development of new agents and investigation of anticancer, antihypertensive and antituberculosis activities École doctorale et discipline ou spécialité : ED SDM, Chimie-Biologie-Santé - CO 042 Unité de Recherche : Laboratoire de Chimie de Coordination du CNRS (UPR CNRS 8241) Directrices de Thèse : Pr. Vania Bernardes-Génisson, Pr. Luiz Gonzaga de França Lopes Membres du jury : Pr. Gilles Gasser, Professeur à Université Chimie Paris Tech, Rapporteur Professeur à “Pontifícia Universidade Católica do Pr. Pablo Machado, Rapporteur Rio Grande do Sul”, Pr. Maria Conceição F. de Professeur à l’”Universidade Federal do Ceará”, Examinatrice Oliveira, Pr. Eric Benoist, Professeur à l’Université de Toulouse III, Examinateur Pr. Vania Bernardes-Génisson, Professeur à l’Université de Toulouse III, Directrice Pr. Luiz Gonzaga de F. Lopes, Professeur à l’”Universidade Federal do Ceará”, Co-directeur Pr. Remi Chauvin, Professeur à l’Université de Toulouse III, Invité Pr. Eduardo Henrique S. de Professeur à l’”Universidade Federal do Ceará”, Invité Sousa, Ce travail consiste en une thèse en cotutela entre les institutions “Universidade Federal do Ceará” (UFC) et Université Paul Sabatier – Toulouse III (UPS-III) financée par la “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior” (CAPES, Brésil) et le Comité Français d'Evaluation de la Coopération Universitaire avec le Brésil (COFECUB, France), Projet n° Ph-C 883/17. ______________________________________________________________ This work consists of a thesis in cotutela between the “Universidade Federal do Ceará” (UFC) and “Université Paul Sabatier – Toulouse III” (UPS-III) institutions funded by the “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior” (CAPES, Brazil) and “Comité Français d’Evaluation de la Coopération Universitaire avec le Brésil” (COFECUB, France), Project n° Ph-C 883/17. UFC UPS-III Acknowledgment _________________________________________________________________________________ Acknowledgment After an intensive work, my PhD is nearing its end. In that time, my knowledge at Chemistry as well as my experimental and research skills have been significantly improved. At this moment, I take this opportunity to thank all the people who directly or indirectly helped me to finish one of the most important stages of my life. First of all, I would like to express my most sincere and immeasurable gratitude to my supervisors, Prof. Vania Bernardes-Génisson, Prof. Luiz Gonzaga de França Lopes, Prof. Eduardo Henrique Silva de Sousa, and Prof. Remi Chauvin, for their support, encouragement, companionship, and helpfulness. Whenever I needed, they were always available to help me, both in academic and personal life. My first steps in academic life were guided and assisted by Prof. Eduardo Sousa. Without a doubt, he is one of my greatest references. Thank you very much for choosing me and helping me evolve. Without his help, it would not have been possible for me to complete my PhD. His contribution to this thesis is notorious. After my graduation, I had (and still have) the honor of starting and finishing the Master's degree with Prof. Luiz Lopes, who is also my Brazilian PhD supervisor. His knowledge, enthusiasm and encouragement helped me to get firm until this moment. I am also extremely grateful for accepting me as a student and for helping me write this thesis. Prof. Vania Bernardes-Génisson was one of the most important and significant professionals that I have had the privilege of knowing as a student. I have no words to express how grateful I am for welcoming me as a student (not to mention as a son) during my doctoral studies in France. Always concerned and attentive to whether the research was going well, but her care was not limited to academic life. On several occasions she supported me especially in the most difficult and troubled moments of my stay in France. I cannot fail to mention the dedication and professionalism in writing this thesis, it is not possible to briefly explain how much of your love and time were invested in this work. Thank you so much for everything. Prof. Remi Chauvin, one of the greatest chemists in the world, sometimes I find myself without believing that I had the time to work and share a phase of my life with you. Your creativity and enthusiasm are contagious. Doing science by your side was an incredible experience. Thank you very much for the discussions and for helping me to evolve as a chemist and person. In addition, I could not fail to mention the good atmosphere at the lab. Thank you very much for opening the doors of your laboratory 3 Acknowledgment _________________________________________________________________________________ for me and for guiding me throughout this stage. From my arrival in France to writing this thesis, your contributions were and are extremely important to me. I sincerely feel honored to have been your doctoral student. In addition, I would like to thank the members of my thesis committee: Prof. Maria Conceição F. de Oliveira (“Universidade Federal do Ceará”, Brazil), Prof. Gilles Gasser (“Université Chimie Paris Tech”, France), Prof. Pablo Machado (“Pontifícia Universidade Católica do Rio Grande do Sul”, Brazil), and Prof. Eric Benoist (“Université de Toulouse III”, France), for having accepted the invitation to participate in this defense, contributing in an insightful and significant way in improving this work. I would like to thank all members of the “Bioinorgânica” group at the “Universidade Federal do Ceará”: the professors Alda Karine, Francisco Audísio, Izaura Diógenes, Idalina Carvalho, Jackson Rodrigues, Tércio Paulo and Elisane Longhinotti, your contributions were essential in my academic life. I have to thank all my friends from the lab. “Bioinorgânica”: Aurideia, Florêncio, Gilmara, Josi, Maiara, Monilson, Ricardo, Walysson, Lucas, Patty, Alan, Giam, Iury, Leonardo, Manigat, Wellison, Karol, Dieric, Juliana, Geângela, Vitória, Carlos Daniel, Vivânia, Mikael and André Florêncio. Directly or indirectly, all of you contributed to this moment. I would like to thank Prof. Tércio Paulo for his help in several experiments both in Brazil and in France, as well as his wife, Mari. The moments we shared in France were extremely important for me, especially when it comes to a situation where you are far from your family and friends. Finally, we became good friends. I would like to say thanks to the friends that France gave me: Cécile, Marwa, Chongwei, Dmytro, Abdelhak, Sameh, Amal, Sarah and Hend. You have helped me a lot to endure the difficulties of distance from home. In particular, I would like to extend my most sincere thanks to my “sisters” Cécile and Marwa, and my “brother” Abdelhak. I consider you as part of my family. I also have to say thanks Valerie for always being available to help me inside and outside the lab. I also have to thank my friend Jéssica de Lima for helping, supporting and crying with me in the moments that I most needed. You are very important to me. I would like to thank the “Universidade Federal do Ceará - UFC” for all the support it has offered me during these more than 10 years. It was literally a second home for me. I also would like to thank “Laboratoire de Chimie de Coordination – LCC” and “Centre National de la Recherche Scientifique – CNRS” for providing a safe 4 Acknowledgment _________________________________________________________________________________ and comfortable workplace, and “Université Paul Sabatier III - UPS” for offering us various interesting and useful courses and training. I am also indebted to Dr. Alix Sournia Saquet and Dr. Lionel Rechignat, their involvement and contributions in the electrochemistry and EPR experiments, respectively were essential. I would like to thank Prof. David A. Wink and his team for the antiangiogenic activity experiments, Prof. Nilberto Robson Falcão do Nascimento and his team for vasodilation tests, Professors Cristiano V. Bizarro and Pr. Luiz A. Basso for anti-TB tests, and Mrs Sandra Bourgeade-Delmas and Prof. Nicolas Fabre for cytotoxicity, anti- leishmaniasis and anti-malaria tests.
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