Investigation of Novel Quinoline–Thiazole Derivatives as Antimicrobial Agents: In Vitro and In Silico Approaches

[Image: see text] Infectious diseases are a major concern around the world. Today, it is an urgent need for new chemotherapeutics for infectious diseases. Because of that, our group designed, synthesized, and analyzed 14 new quinoline derivatives endowed with the pharmacophore moiety of fluoroquinolones primarily for their antimicrobial effects. Their cytotoxicity effects were tested against six bacterial and four fungal strains and NIH/3T3 cell line. Additionally, their action mechanisms were evaluated against DNA gyrase and lanosterol 14α-demethylase (LMD). Furthermore, to eliminate the potential side effects, the active compounds were evaluated against the aromatase enzyme. The experimental enzymatic results were evaluated for active compounds’ binding modes using molecular docking and molecular dynamics simulation studies. The results were utilized to clarify the structure–activity relationship (SAR). Finally, compound 4m was the most potent compound for its antifungal activity with low cytotoxicity against healthy cells and fewer possible side effects, while compounds 4j and 4l can be used alone for special patients who are suffering from fungal infections in addition to the primer disease.