Synthesis and investigation of pharmacological effects ofnew pyrimidinylthiomethyl thiazole derivatives

Purine and pyrimidine bases form the main structure of the most vital molecules of the body. There are many active molecules developed on the basis of these structures. Uracil, cytosine and thiouracil are important heterocyclic pharmacophores having pharmacological diversity within this chemical group. As one of these pharmacological effects, adenosine have important functions on many systems such as central nervous system, kidney, cardiovascular system, tumor cells. These effects occur through 4 subtypes of G protein-coupled receptors. Crystallographic data of the adenosine A2A and A1 receptor are available. Thus, numerous studies have been conducted to develop receptor agonists and antagonists. In most of these compounds, there is a ribose moiety have ribose moiety. Non-ribose compounds such as capadenoson have also been published. Compounds synthesized within the scope of this thesis are new chemical bioactive structures designed based on biologically active (antitumor, antiviral, etc.) 5-cyanothiouracil analogs and non-ribose-bearing adenosine receptor ligands. Antitumor activity of 33 synthesized compounds on U87 MG glioblastoma cell line was determined. Adenosine receptor binding affinity of 11 compounds (4, 12, 25-33) which were active (13-44% viability, 50 µM) were also measured to investigate the biochemical basis of their antitumor effect. With the evaluation of the obtained results, it is planned to develop experimental studies and optimize the compounds. Keywords: Thiouracil, Pyrimidine, Thiazole, Glioblastoma, Adenosine