Synthesis and characterization of molecules containing a quinoline ring with potential biological activity

Heterocyclic compounds are found in the structures of biomolecules such as DNA, RNA, vitamins, and hormones constitute an important class of organic chemistry. Among these compounds, the quinoline skeleton is one of the most commonly used N-heterocyclic structures with high activity in industrial and medical applications. Quinoline rings are frequently encountered in both naturally occurring compounds and synthetic drugs. It is well known that quinoline derivatives exhibit biological activities such as anticancer, antimalarial, antibiotic, and anti-HIV effects. In this thesis, 2-amino-4-hydroxyquinoline-3-carbonitrile compounds were synthesized starting from N-(2-aminobenzoyl)benzotriazole derivatives, followed by the reaction of these compounds with POCl3 to obtain 2-amino-4-chloroquinoline-3-carbonitrile derivatives. From these 2-amino-4-chloroquinoline-3-carbonitrile derivatives, 20 new quinoline derivatives with yields ranging from 23% to 92% were synthesized to contribute to the literature. The structures of the synthesized compounds were elucidated using spectroscopic methods such as IR, ¹H NMR, ¹³C NMR, and HRMS. Furthermore, the cytotoxic effects of these compounds on A549, MCF7, and NIH3T3 cell lines, as well as their EGFR enzyme inhibition activities, were investigated. The compound exhibiting the strongest inhibition effect on the EGFR enzyme was analyzed for its interactions and binding sites in the active region of the enzyme using molecular docking studies. Additionally, all synthesized compounds were subjected to computational calculations using the DFT method. As a result of these calculations, MEP maps, HOMO-LUMO energy gaps, and theoretical NMR chemical shift values of the compounds were obtained.