Work

Pharmacological screening of compounds, new thiazole derivatives, for antitumor activity showed their highly selective effect on various mammalian cancer cell lines, in particular, uterine, rectal and glioblastoma cancer cells. A common feature in tumor cells of these and other lines that are most affected by "hit compounds" is the modification of the promoter region of the MGMT gene, which encodes the protein O (6) -methylguanine-DNA methyltransferase (MGMT). The consequence of it- its reduced synthesis. This feature of malignant cells is one of the mechanisms involved in the emergence of cell resistance to chemotherapy on the one hand, and on the other - is crucial for predicting the sensitivity of tumor cells to alkylating agents and will be used to investigate the mechanism of action of test substances. To do this, it is planned to conduct research in the following stages: 1. The study of the effect of new thiazole derivatives with a pyridine fragment on cell lines with normal and altered level of MGMT synthesis. 2. Study of the effect of thiazole derivatives with a pyridine fragment on the expression of proteins involved in cell reparation, chromatin remodeling and apoptosis by Western blot analysis, determination of total DNA methylation in cells and MGMT synthesis by action of new thiazole derivatives by polymerase reactions. According to the above stages of the project, it is expected that the newly synthesized substances will be recommended for further clinical trials, and in case of positive results, can be introduced to the Ukrainian pharmaceutical market as antitumor drugs with increased efficiency and selectivity. In addition, the implementation of the project will help deepen partnerships between research institutions. The results of scientific research are also expected to be published in journals indexed in Scopus and / or Web of Science scientometric databases.