|
|
Pyrazine Carbonyl Compounds - Building Blocks in Dynamic Combinatorial Systems
Coufal, Radek ; Drahoňovský, Dušan (advisor) ; Jindřich, Jindřich (referee)
This bachelor thesis deals with the synthesis of bifunctional carbonyl derivatives of pyrazine, which are further examined for their potential to form dynamic hemiacetals with monofunctional alcohols. Newly prepared, in the literature not yet described bifunctional trifluormethyl derivatives exhibit considerable ability to form hemiacetals in a dynamic system. The obtained results show that these substances may find application as building blocks of dynamic combinatorial systems.
|
|
|
Creation and analysis of in-house database of pyrazine derivatives with potential antimicrobial activity
Kebakuile, Legae Gomolemo Boemo ; Zitko, Jan (advisor) ; Kučerová, Marta (referee)
In the early phases of drug design and development, scientists must overcome many challenges involved in identifying potential drug-like or lead-like compounds. This has led to the need of creating large sets of chemical data which will aid in improving the identification of pharmacophores and active compounds. Various scientific fields especially pharmacology, medicinal chemistry and biochemistry have begun to employ the use of computer sciences to aid in the screening for potential leads with more specificity with regards to drug-like compounds' or substances' bioactivity. The emphasis of this project was to create a database containing a collection of pyrazine compounds synthesized overtime in the Faculty of Pharmacy (Charles University, Hradec Kralove) with the aim of having anti-mycobacterium (and possible antibacterial and antifungal) activity, and further utilize this database to predict certain pharmacokinetic and bioavailability properties. This project seeks to demonstrate how certain molecular descriptors can be used as reliable chemoinformation to determine the likeliness or possibility of developing a lead-like or drug-like compound by utilizing computer software. An in-house database of 623 compounds saved in SMILES format was created and used in demonstrating quantitative...
|
|
|
Design, synthesis and biological evaluation of 2,3-disubstituted pyrazines
Kerda, Marek ; Zitko, Jan (advisor) ; Kučerová, Marta (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Supervisor: Assoc. Prof. PharmD. Jan Zitko, PhD. Author: Marek Kerda Title of diploma thesis: Design, synthesis and biological evaluation of 2,3-disubstituted pyrazines This thesis deals with problem of tuberculosis. In a theoretical part are summarized information and knowledge about tuberculosis, nowadays epidemiology and drugs used in current treatment. There are also described drugs in the different stage of clinical trials and could be used for treatment of tuberculosis in the future. Searched information were used from accessible learning materials and in articles in online databases as Web of Science and PubMed. There are also summarized basic methods of computer design of new drugs. In practical part of this thesis was focus on novel inhibitor of prolyl-tRNA synthetase, which is based on structure of pyrazinamide. There was prepared in silico virtual library of pyrazine-based new potential ligands. Related docking to the structure of human prolyl t-RNA (pdb: 5VAD) and the bacterial version of this enzyme (pdb: 2J3M) and evaluation was performed in Molecular Operating Environment (Chemical Computing Group, Canada). From the results were predicted some of the relations between structure and activity. Virtual library of the...
|
|
|
Creation and analysis of in-house database of pyrazine derivatives with potential antimicrobial activity
Kebakuile, Legae Gomolemo Boemo ; Zitko, Jan (advisor) ; Kučerová, Marta (referee)
In the early phases of drug design and development, scientists must overcome many challenges involved in identifying potential drug-like or lead-like compounds. This has led to the need of creating large sets of chemical data which will aid in improving the identification of pharmacophores and active compounds. Various scientific fields especially pharmacology, medicinal chemistry and biochemistry have begun to employ the use of computer sciences to aid in the screening for potential leads with more specificity with regards to drug-like compounds' or substances' bioactivity. The emphasis of this project was to create a database containing a collection of pyrazine compounds synthesized overtime in the Faculty of Pharmacy (Charles University, Hradec Kralove) with the aim of having anti-mycobacterium (and possible antibacterial and antifungal) activity, and further utilize this database to predict certain pharmacokinetic and bioavailability properties. This project seeks to demonstrate how certain molecular descriptors can be used as reliable chemoinformation to determine the likeliness or possibility of developing a lead-like or drug-like compound by utilizing computer software. An in-house database of 623 compounds saved in SMILES format was created and used in demonstrating quantitative...
|
|
|
Synthesis and antiinfective evaluation of substituted N-(pyrazin-2-yl)benzenesulfonamides
Paredes De La Red, Cristina ; Doležal, Martin (advisor) ; Kučerová, Marta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Cristina Paredes de la Red Supervisor: prof. PharmDr. Martin Doležal, Ph.D. Title of diploma thesis: Synthesis and antiinfective evaluation of substituted N-(pyrazine-2- yl)benzenesulfonamide Tuberculosis (TB) is among the ten leading causes of death, especially in developing countries. Even though it is an old disease with established treatment regimen, there has been an increased resistance to anti-TB drugs 1 . The anti-tubercular pyrazinamide has caught the attention of researchers as the different theories for its mechanism of action have made it an interesting entity for further investigation. Here we will discuss N-(pyrazine-2-yl)benzenesulfonamides (General structure is presented in the Figure below) as a new derivatization approach based on synergism methodology between pyrazinamide and sulfonamides. Sulfonamides exert their antimicrobial effect by competitive inhibition of folic acid synthesis and subsequent inhibition of bacterial growth and reproduction 18 . I have contributed to the synthesis and purification of 8 compounds in a series of total 22 N- pyrazinylsulfonamides. Two of the prepared compounds showed activity against Mycobacterium kansasii [2a (MIC...
|
|
|
Chemical aposematism: reactions of predators towards chemical warning signals of prey
Chalušová, Kateřina ; Exnerová, Alice (advisor) ; Kotyková Varadínová, Zuzana (referee)
An aposematism is a type of defence mechanism, by which a prey demonstrates towards predator that it is unpalatable and toxic. The reactions of predators towards chemical warning signals of prey differ due to the quantity and a combination of signals showed by prey, the predator species and its primary orientation. Most of works tested reactions of birds towards gustatory and olfactory stimuli, often in combination with signals from other modalities. Although the birds are predators which orientate primarily visually, olfaction, gustation and chemesthesis significantly helped them with determining unpalatable food. Among other tested predators were fish, amphibians, reptiles, mammals and invertebrates and their reactions towards the same chemicals of prey are noted for comparison. The main chemicals used in the experiments regarding birds were denatonium benzoate (Bitrex), quinin and pyrazines. Predators often showed an aversive behaviour, neophobic reactions, accelerated learning and more effective memorizing of the unpalatable prey if it was presented together with chemical signals. Some of the predators were able to control their toxin intake relative to the amount of toxin ingested or to discriminate between palatable and unpalatable food according to the chemical concentration in it. Key...
|
|
|
Pyrazine Carbonyl Compounds - Building Blocks in Dynamic Combinatorial Systems
Coufal, Radek ; Drahoňovský, Dušan (advisor) ; Jindřich, Jindřich (referee)
This bachelor thesis deals with the synthesis of bifunctional carbonyl derivatives of pyrazine, which are further examined for their potential to form dynamic hemiacetals with monofunctional alcohols. Newly prepared, in the literature not yet described bifunctional trifluormethyl derivatives exhibit considerable ability to form hemiacetals in a dynamic system. The obtained results show that these substances may find application as building blocks of dynamic combinatorial systems.
|
guest ::
