|
|
Inhibitors of mitochondrial enzymes as potential therapeutics for Alzheimer's disease
Hroch, Lukáš ; Musílek, Kamil (advisor) ; Farsa, Oldřich (referee) ; Zimčík, Petr (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Department of Pharmaceutical Chemistry and Drug Control Candidate Mgr. Lukáš Hroch Supervisor assoc. prof. PharmDr. Kamil Musílek, Ph.D. Title of Doctoral Thesis Inhibitors of mitochondrial enzymes as potential therapeutics for Alzheimer's disease There were about 50 million people living with dementia in 2015. It is expected that number of people living with dementia will reach 130 million by the year of 2050. Alzheimer's disease (AD) is one of the most common causes of dementia and it is estimated to account for about 60 80% of overall cases. Current symptomatic treatment only alleviates symptoms and delays progression of the disease. However, there is no effective treatment, which would address the underlying cause of AD. The extracellular depositions of insoluble amyloid beta peptide (Aβ) were thought to be a causative factor and main target for a long time. Yet, targeted treatment towards the reduction of extracellular Aβ depositions failed to show expected therapeutic merit. Later on, it has been shown that development of AD starts much earlier than any Aβ plaques or symptoms could be observed. With growing evidence of soluble Aβ in intracellular regions, main attention moved to investigations of Aβ within the cells. Aβ...
|
|
|
Derivatives of pyrazine as potential antituberculars (preparation and study of biological properties)
Janďourek, Ondřej ; Doležal, Martin (advisor) ; Farsa, Oldřich (referee) ; Musílek, Kamil (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Candidate Mgr. Ondřej Janďourek Supervisor Prof. PharmDr. Martin Doležal, Ph.D. Consultant PharmDr. Jan Zitko, Ph.D. Title of Doctoral Thesis Derivatives of pyrazine as potential antituberculars (preparation and study of biological properties) This work is focused on pyrazine derivatives with the structural relationship to pyrazinamide (PZA) and with the potential antitubercular effect. In the introduction, there are summarized theoretical findings about tuberculosis (TBC), its epidemiology and primarily the development of resistance to current pharmacotherapy. Brief overview of known antituberculars, novel compounds and auspicious molecules in clinical trials is outlined. PZA, which is counted among the first line antitubercular agents, is widely described due to its cardinal role in this thesis. PZA possible mechanisms of action are described together with its pharmacological profile. Finally, brief summary of already prepared derivatives of PZA is stated. Practical part of this thesis is focused on synthesis of three starting compounds (5-chloro-6-methylpyrazine-2,3-dicarbonitrile; 3-chloropyrazine-2-carboxamide; N-benzyl-3-chloropyrazine-2-carboxamide) that were...
|
|
|
In silico studies of cholinesterases interactions with their modulators and design of new compounds of this type
Binder, Jiří ; Opletalová, Veronika (advisor) ; Farsa, Oldřich (referee) ; Vinšová, Jarmila (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical analysis Candidate: Mgr. Jiří Binder Supervisor: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Title of Doctoral Thesis: In silico studies of cholinesterases interactions with their modulators and design of new compounds of this type Computer modeling is an important tool of contemporary scientific research. It allows to study the structure, conformation, dynamics and mutual interaction of nonbinding interactions of a biological system. The main objective is to find the best energy conformations by minimizing the energy of the system. On the base of these calculated values, one can predict the loss of activity for certain analogous compounds, thus reducing the number of materials that would be needed to subsequently synthesize. A molecular modeling contributes to describe the interactions of ligands with larger systems and improves the orientation in millions of active substances that could be used as potential drug. It becomes an important part of the pharmaceutical industry. The aim of this study was to verify the selected methodology of computer prediction of protein-ligand complexes, to obtain a description of the basic interactions of the modulators of cholinesterase...
|
|
|
Inhibitors of mitochondrial enzymes as potential therapeutics for Alzheimer's disease
Hroch, Lukáš ; Musílek, Kamil (advisor) ; Farsa, Oldřich (referee) ; Zimčík, Petr (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Department of Pharmaceutical Chemistry and Drug Control Candidate Mgr. Lukáš Hroch Supervisor assoc. prof. PharmDr. Kamil Musílek, Ph.D. Title of Doctoral Thesis Inhibitors of mitochondrial enzymes as potential therapeutics for Alzheimer's disease There were about 50 million people living with dementia in 2015. It is expected that number of people living with dementia will reach 130 million by the year of 2050. Alzheimer's disease (AD) is one of the most common causes of dementia and it is estimated to account for about 60 80% of overall cases. Current symptomatic treatment only alleviates symptoms and delays progression of the disease. However, there is no effective treatment, which would address the underlying cause of AD. The extracellular depositions of insoluble amyloid beta peptide (Aβ) were thought to be a causative factor and main target for a long time. Yet, targeted treatment towards the reduction of extracellular Aβ depositions failed to show expected therapeutic merit. Later on, it has been shown that development of AD starts much earlier than any Aβ plaques or symptoms could be observed. With growing evidence of soluble Aβ in intracellular regions, main attention moved to investigations of Aβ within the cells. Aβ...
|
|
|
Inhibitors of mitochondrial enzymes as potential therapeutics for Alzheimer's disease
Hroch, Lukáš ; Musílek, Kamil (advisor) ; Farsa, Oldřich (referee) ; Zimčík, Petr (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Department of Pharmaceutical Chemistry and Drug Control Candidate Mgr. Lukáš Hroch Supervisor assoc. prof. PharmDr. Kamil Musílek, Ph.D. Title of Doctoral Thesis Inhibitors of mitochondrial enzymes as potential therapeutics for Alzheimer's disease There were about 50 million people living with dementia in 2015. It is expected that number of people living with dementia will reach 130 million by the year of 2050. Alzheimer's disease (AD) is one of the most common causes of dementia and it is estimated to account for about 60 80% of overall cases. Current symptomatic treatment only alleviates symptoms and delays progression of the disease. However, there is no effective treatment, which would address the underlying cause of AD. The extracellular depositions of insoluble amyloid beta peptide (Aβ) were thought to be a causative factor and main target for a long time. Yet, targeted treatment towards the reduction of extracellular Aβ depositions failed to show expected therapeutic merit. Later on, it has been shown that development of AD starts much earlier than any Aβ plaques or symptoms could be observed. With growing evidence of soluble Aβ in intracellular regions, main attention moved to investigations of Aβ within the cells. Aβ...
|
|
|
Derivatives of pyrazine as potential antituberculars (preparation and study of biological properties)
Janďourek, Ondřej ; Doležal, Martin (advisor) ; Farsa, Oldřich (referee) ; Musílek, Kamil (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Candidate Mgr. Ondřej Janďourek Supervisor Prof. PharmDr. Martin Doležal, Ph.D. Consultant PharmDr. Jan Zitko, Ph.D. Title of Doctoral Thesis Derivatives of pyrazine as potential antituberculars (preparation and study of biological properties) This work is focused on pyrazine derivatives with the structural relationship to pyrazinamide (PZA) and with the potential antitubercular effect. In the introduction, there are summarized theoretical findings about tuberculosis (TBC), its epidemiology and primarily the development of resistance to current pharmacotherapy. Brief overview of known antituberculars, novel compounds and auspicious molecules in clinical trials is outlined. PZA, which is counted among the first line antitubercular agents, is widely described due to its cardinal role in this thesis. PZA possible mechanisms of action are described together with its pharmacological profile. Finally, brief summary of already prepared derivatives of PZA is stated. Practical part of this thesis is focused on synthesis of three starting compounds (5-chloro-6-methylpyrazine-2,3-dicarbonitrile; 3-chloropyrazine-2-carboxamide; N-benzyl-3-chloropyrazine-2-carboxamide) that were...
|
|
|
In silico studies of cholinesterases interactions with their modulators and design of new compounds of this type
Binder, Jiří ; Opletalová, Veronika (advisor) ; Farsa, Oldřich (referee) ; Vinšová, Jarmila (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical analysis Candidate: Mgr. Jiří Binder Supervisor: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Title of Doctoral Thesis: In silico studies of cholinesterases interactions with their modulators and design of new compounds of this type Computer modeling is an important tool of contemporary scientific research. It allows to study the structure, conformation, dynamics and mutual interaction of nonbinding interactions of a biological system. The main objective is to find the best energy conformations by minimizing the energy of the system. On the base of these calculated values, one can predict the loss of activity for certain analogous compounds, thus reducing the number of materials that would be needed to subsequently synthesize. A molecular modeling contributes to describe the interactions of ligands with larger systems and improves the orientation in millions of active substances that could be used as potential drug. It becomes an important part of the pharmaceutical industry. The aim of this study was to verify the selected methodology of computer prediction of protein-ligand complexes, to obtain a description of the basic interactions of the modulators of cholinesterase...
|
|
|
In silico studies of cholinesterases interactions with their modulators and design of new compounds of this type
Binder, Jiří ; Opletalová, Veronika (advisor) ; Farsa, Oldřich (referee) ; Vinšová, Jarmila (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical analysis Candidate: Mgr. Jiří Binder Supervisor: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Title of Doctoral Thesis: In silico studies of cholinesterases interactions with their modulators and design of new compounds of this type Computer modeling is an important tool of contemporary scientific research. It allows to study the structure, conformation, dynamics and mutual interaction of nonbinding interactions of a biological system. The main objective is to find the best energy conformations by minimizing the energy of the system. On the base of these calculated values, one can predict the loss of activity for certain analogous compounds, thus reducing the number of materials that would be needed to subsequently synthesize. A molecular modeling contributes to describe the interactions of ligands with larger systems and improves the orientation in millions of active substances that could be used as potential drug. It becomes an important part of the pharmaceutical industry. The aim of this study was to verify the selected methodology of computer prediction of protein-ligand complexes, to obtain a description of the basic interactions of the modulators of cholinesterase...
|
|
|
Derivatives of pyrazine as potential antituberculars (preparation and study of biological properties)
Janďourek, Ondřej ; Doležal, Martin (advisor) ; Farsa, Oldřich (referee) ; Musílek, Kamil (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Candidate Mgr. Ondřej Janďourek Supervisor Prof. PharmDr. Martin Doležal, Ph.D. Consultant PharmDr. Jan Zitko, Ph.D. Title of Doctoral Thesis Derivatives of pyrazine as potential antituberculars (preparation and study of biological properties) This work is focused on pyrazine derivatives with the structural relationship to pyrazinamide (PZA) and with the potential antitubercular effect. In the introduction, there are summarized theoretical findings about tuberculosis (TBC), its epidemiology and primarily the development of resistance to current pharmacotherapy. Brief overview of known antituberculars, novel compounds and auspicious molecules in clinical trials is outlined. PZA, which is counted among the first line antitubercular agents, is widely described due to its cardinal role in this thesis. PZA possible mechanisms of action are described together with its pharmacological profile. Finally, brief summary of already prepared derivatives of PZA is stated. Practical part of this thesis is focused on synthesis of three starting compounds (5-chloro-6-methylpyrazine-2,3-dicarbonitrile; 3-chloropyrazine-2-carboxamide; N-benzyl-3-chloropyrazine-2-carboxamide) that were...
|
guest ::
