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Synthesis of novel viral methyltransferase inhibitors
Kocek, Hugo ; Nencka, Radim (advisor) ; Česnek, Michal (referee)
Methyltransferases (MTases) are a class of enzymes that catalyze methylation of their substrates. These enzymes are found in all living organisms (including some viruses) as methylations are involved in numerous biological processes. Therefore, MTases are attractive targets for medicinal chemistry. Currently, only inhibitors of human MTases are used in medicine, for example, 5-azacytidine targeting DNA-MTase. However, viral MTases are potential drug targets as well. They enable viruses to escape the immune system and to use the host's translation machinery. As a consequence of the SARS-CoV-2 pandemic, coronaviral MTases became the center of attention, followed by the Mpox virus, which spread in the population in 2022. This thesis is focused on the synthesis of potential MTase inhibitors derived from adenosine-5'-carboxylic acid. The primary target is SARS-CoV-2 nsp14, however, the compound library will be used for screening against other MTases as well. Key words: methyltransferase; inhibitor; SARS-CoV-2; medicinal chemistry
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Setting up educational materials for the topic Chemistry around us
Štefková, Ivona ; Šmejkal, Petr (advisor) ; Smrček, Stanislav (referee) ; Richtr, Václav (referee)
This dissertation deals with the creation of educational materials to topics from the field Chemistry around us and circumstances of its implementation into teaching chemistry with regard to the needs posed by curricular documents. The connection between real world and the content of the chemistry subject, which is taught at schools, is shown on the curricular topics related to medicinal chemistry and to fertilizer chemistry. This could make the student getting a better overview of the subject itself. Regarding the specialist and didactical part, the teaching material tries to make it easier for the teacher to prepare for the lessons and make them more interesting due to the teaching material's variability and processing (teaching text, powerpoint presentations, plays, laboratory exercises etc.). This way, the student gains access to practical topics through various types of exercises, interesting aspects, plays etc. The evaluation of educational materials and investigation of student's and teacher's attitude was carried out via a questionnaire investigation. The investigation showed that both students and teachers regard these topics as beneficial and belonging to the field of chemistry. The medicinal topics were approached by the girls better than by the boys, which was not the case of the...
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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...
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Development of new glycosylation methods for the synthesis of nucleosides
Downey, Alan Michael ; Hocek, Michal (advisor) ; Křen, Vladimír (referee) ; Kočovský, Pavel (referee)
As they make up DNA and RNA, nucleosides are considered the key to life. Synthetic nucleosides also constitute many drugs that treat viral infections and cancer. As a result, more efficient methods to access these crucial molecules would have implications that extend beyond a synthetic chemist's benchtop and into medicinal chemistry and medical research. One of the most challenging steps in the synthesis of nucleosides is the glycosylation step between the acceptor heterocycle (nucleobase) and the saccharide-based donor. Often to obtain satisfactory yield of this step with good regio- and stereochemical control the extensive use of protecting groups must be employed to squelch reactivity at unwanted reactive groups. Consequently, this process of protection−glycosylation−deprotection is laborious, inefficient, and often requires the use of toxic reagents. It would be, therefore, highly welcomed if new methodology to effect this glycosylation step was designed that reduces or removes the need to use protecting groups, but would still provide nucleosides in good yield, regio- and stereoselectively. Herein, this thesis presents my efforts into achieving this end. By employing modified Mitsunobu conditions, I determined that it is possible to directly glycosylate a nucleobase with D-ribose to afford...
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Setting up educational materials for the topic Chemistry around us
Štefková, Ivona ; Šmejkal, Petr (advisor) ; Smrček, Stanislav (referee) ; Richtr, Václav (referee)
This dissertation deals with the creation of educational materials to topics from the field Chemistry around us and circumstances of its implementation into teaching chemistry with regard to the needs posed by curricular documents. The connection between real world and the content of the chemistry subject, which is taught at schools, is shown on the curricular topics related to medicinal chemistry and to fertilizer chemistry. This could make the student getting a better overview of the subject itself. Regarding the specialist and didactical part, the teaching material tries to make it easier for the teacher to prepare for the lessons and make them more interesting due to the teaching material's variability and processing (teaching text, powerpoint presentations, plays, laboratory exercises etc.). This way, the student gains access to practical topics through various types of exercises, interesting aspects, plays etc. The evaluation of educational materials and investigation of student's and teacher's attitude was carried out via a questionnaire investigation. The investigation showed that both students and teachers regard these topics as beneficial and belonging to the field of chemistry. The medicinal topics were approached by the girls better than by the boys, which was not the case of the...
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