According to the World Health Organization (WHO), in 2018 cancer was the second leading cause of death, causing over 9.6 million deaths worldwide. The continuous increase in multidrug resistance of tumors, as well as dynamically changing epigenetic factors, create the need to search for new, more selective anticancer compounds. A promising target for drugs used in cancer therapy is telomerase, playing a key role in the process of cell proliferation, homeostasis and tumor transformation. Cancer cells, unlike normal cells, are characterized by short telomeres. This creates the possibility of blocking, the process of carcinogenesis by inhibiting the activity of telomerase without side effects for normal cells. Inhibition of the enzyme in cancer cells can lead to a decrease in telomere length and, consequently, to cell ageing and apoptosis. One of the methods of telomerase inhibition is the use of small-molecule chemical compounds targeting the hTERT telomerase catalytic subunit, responsible for enzymatic activity. Although this subunit has been exhaustively researched as a molecular target, so far none of the promising molecules has been registered as a drug. Therefore, there is still a need for new compounds that are inhibitors of telomerase, and in particular of this subunit. The aim of the proposed research is to evaluate the cellular response to the new 9,10-anthraquinone derivatives in order to determine the molecular mechanism of action of these compounds. Numerous reports indicate anthraquinone derivatives as telomerase inhibitors, but our preliminary results show that the new anthraquinone derivatives exhibit a completely different telomerase inhibition mechanism than other known compounds of this chemical class. The study will bring fully original and novel results important for extending our knowledge on the new small-molecules telomerase inhibitors from the anthraquinone class, which could be a good starting point for further development of new anticancer agents targeting telomere.
Details
- Financial Program Name:
- PRELUDIUM
- Organization:
- Narodowe Centrum Nauki (NCN) (National Science Centre)
- Agreement:
- UMO-2021/41/N/NZ7/03707 z dnia 2021-11-26
- Realisation period:
- 2021-11-26 - 2024-11-25
- Project manager:
- dr inż. Natalia Maciejewska
- Realised in:
- Department of Pharmaceutical Technology and Biochemistry
- Request type:
- National Research Programmes
- Domestic:
- Domestic project
- Verified by:
- Gdańsk University of Technology
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