Grynyukova A. Cytotoxic effect of long-chain imidazole derivatives as potential anticancer agents with a selective type of action: in silico and in vitro studies

The Ph.D. thesis is dedicated to the current scientific and practical problem of targeted search, analysis, and investigation of biologically active long-chain derivatives of imidazole and pyridine as potential target-oriented anticancer agents with a selective type of action. In this thesis, the anticancer potential of long-chain imidazole derivatives was demonstrated by using in silico and in vitro methods as a selective anticancer agents against human neuroblastoma, myelogenic leukemia, and laryx adenocarcinoma. The studied test articles has demonstrated a selective cytotoxic effect against neuroblastoma, myelogenous leukemia, and adenocarcinoma of the human larynx. With respect to acquired in vitro data cytotoxic activity of imidazolium derivatives against human neuroblastoma (SK-N-DZ), human epidermoid carcinoma of the larynx (HEp-2) and human myelogenous leukemia (K562), a relationship between the anticancer properties of the studied imidazole derivatives and the characteristics of their chemical structure have been established. The newly developed QSAR models of anticancer effect of imidazolium derivatives against neuroblastoma, myelogenous leukemia and human adenocarcinoma, with high predictive ability, have been made available on the OСHEM server for free access by researchers working in the field of anticancer drug discovery and development. These models are presented as a tool for the search and analysis of new anticancer agents with relevant structures and mechanisms of action. The antioxidant effect and toxicity of the compounds under acute experimental conditions have been investigated.