Sinteza i citostatska ispitivanja biblioteke novih dušikovih heterocikla

Synthesis and cytostatic evaluations of novel nitrogen heterocycles library

Cancer is one of the most serious health problems of a worldwide dimension. One in three of the population develops cancer at some time in their lives and one in four dies from this disease. The main problems in antitumor chemotherapy are drug resistance and side effects on normal tissues. In the recent years a tremendous growth was witnessed in synthesis and development of vast number and types of new heterocyclic antitumor agents, with an emphasis on creation of new drugs with better selectivity or activity. The latter are indeed major requirements in development of novel anticancer drugs. The proposed scientific project is highly interdisciplinary and objective-oriented with the principal aim to develop the novel lead compounds with pronounced and selective anticancer activity that would be used for further phases of drug development. To achieve the principal aim following specific tasks are foreseen. The goal of the first one is to synthesize small-compound library (Classes A–H) comprising new conjugates of pseudopurines, coumarines and quinolines with 1,2,3-triazole scaffold, N-acyclic 5-unsaturated pyrimidine derivatives, amino-, amido- and amidino substituted benzimidazole, benzothiazole and benzo[b]thieno-2-carboxamide derivatives. Molecule library will be synthesized using modern synthetic approaches such as click chemistry, palladium mediated cross-coupling, eco-friendly microwave assisted and photochemical reactions as well as classical organic synthetic methods. The aim of the second task is to predict plausible biological targets and pharmacological activities using cheminformatics/in silico analysis. The third task is to perform cytostatic evaluations based on which hit molecules with desired biological effect will be selected for structure optimization that will be subsequently carried out. Finally, the molecular mechanism studies are anticipated for the most effective compounds from synthesized N-heterocycles library.