Abstrakt

Telomerase plays a pivotal role in cell proliferation, homeostasis, and neoplastic transformation, making it a promising molecular target for cancer chemotherapy. Of note, although hTERT has been explored thoroughly as a target, none of the promising molecules has been approved as a drug until now. The subject of research conducted as part of my doctoral dissertation is explaining the cellular and molecular mechanism of action of new heterocyclic compounds derived from the class of carbazole, pyrazole, and anthraquinone. Of all the candidates tested, only anthraquinones inhibited telomerase activity. I have shown that the most active compound (TXT4), apart from the typical features of telomerase targeting molecules, also preferentially damages DNA on telomeres. Furthermore, I have found that TXT4 has an additional mechanism of action, consisting of multidirectional inhibition of tyrosine kinases. From among carbazoles, I selected compounds 5aa and 8, which primary mechanism of action is reactive oxygen species production. In addition, I showed that the most promising compound from the pyrazole class is PCH-1, whose anticancer activity is based on the stabilization of tubulin polymerization - the cytoskeleton-forming protein. On the basis of the conducted research, I determined the main mechanisms of action of new anti-cancer compounds, which in the future may employ as the basis for the design and synthesis of new potential pharmaceutical agents.

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