Synthesis of new quinoline derivatives and investigation of their antimicrobial and DNA gyrase inhibition effects

Infection is the occurrence of several undesirable effects which caused by pathogenic microorganisms in an organism. Especially bacterial and fungal infections are common. There are many antimicrobial agents used in the treatment of these infections. But today, the effects of these agents are gradually decreasing, and the biggest problem that causes this condition and threatens the world health is the development the different types of resistance to antimicrobial drugs. Quinoline and thiazole have proved their efficiency against microbial infections and were found in the structure of many antimicrobial agents that have been used clinically. Previous studies showed that both rings inhibit the DNA gyrase enzyme and thus they produce the antimicrobial effect. In this study, novel quinoline-thiazole derivatives were synthesized to develop new antimicrobial agents. The thiazole and quinoline rings were combined with the hydrazine bridge to obtain new molecules. The structures of the compounds were illuminated by IR, 1H-NMR, 13C-NMR and high-resolution mass spectroscopy (HRMS). The antimicrobial activities of the compounds were tested against four Candida spp., two gram negative and four gram positive bacteria species. Compounds 4g and 4m showed high antimicrobial activity against E. coli and S. aureus. The pathway of action was also demonstrated by the DNA gyrase inhibition study. At the same time, compounds 4b, 4e, 4f, 4h, 4j and 4m showed anticandidal activity at concentration lower than 0,06 µg /mL. In general, the most active compound was determined as 4m. Keywords: Quinoline, Antimicrobial activity, Thiazole, DNA gyrase, Bacterial topoisomerase, Molecular modelling