Vývoj nových mTOR inhibitorů jako potenciálních léčiv zpomalujících stárnutí

Bc. Veronika Skoupilová

Master's thesis

Development of novel mTOR inhibitors as potential anti-aging drugs

Abstract:

Ageing of human population is a phenomenon that could be a source of various socio-economic issues in the future. Because of this reason it is important to take a look on ageing on its molecular origin. The senescence of cell is a natural process leading to ageing, however, it can be postponed and maybe reverted by senolytics. One of the first senolytic drugs was rapamycin, a drug with immunosuppressive, anticancerogenic and antifungal effect. Therapy with rapamycin was proved to prolong lifespan as well as improve the quality of the life of model organisms. The key to our knowledge are mammalian targets of rapamycin known as mTOR and metabolic pathways related to mTOR. By regulation of these receptors, it is possible to regulate constitutive cell processes from proliferation, cell growth, proteosynthesis, transcription regulation, glucose metabolism and lipid metabolism and other processes. Anomalies in pathways associated with mTOR proved to be a possible way of progression of age-related diseases, for example, cancer, diabetes mellitus type 2 and multiple neurodegenerative diseases. In conclusion, detailed research of mTOR and substances able to regulate mTOR could lead us to a new approach to treat age-related diseases or to their early prevention. The main goal of this Diploma Thesis is in vitro testing of novel compounds (cytotoxicity and indirect inhibition of mTORC1 and mTORC2) as potential mTOR inhibitors targeting ageing. The next aim of the Thesis is to determine the physicochemical properties of given compounds, in particular, log P, log D and pKa.

Keywords

ageing, mTOR, longevity, rapamycin, age-related diseases

Language used: English

Date on which the thesis was submitted / produced: 26. 7. 2021

Thesis defence

• Date of defence: 23. 8. 2021
• Supervisor: Mgr. Eugenie Nepovimová, Ph.D.
• Reader: PharmDr. Rudolf Andrýs, Ph.D.

University of Hradec Králové

Faculty of Science

Master programme / field:
Chemie / Chemie - spec. bioorganická chemie