Design, synthesis, molecular docking, and dynamics studies of novel thiazole-Schiff base derivatives containing a fluorene moiety and the assessment of their antimicrobial and antioxidant activity.

In this study, a series of eighteen fluorene-containing substituted thiazole derivatives were synthesized and characterized spectral analyses. The proposed compounds were screened for their antimicrobial activity, and it was found that compound 2a displayed a significant zone of inhibition (20.3 ± 0.6 mm) against and compound 2b exhibited inhibitory activity (30.3 ± 0.6 mm) against a fungal strain. Furthermore, antioxidant activity was evaluated for all analogues, where 2f exhibited a four-fold higher antioxidant capability (11.73 ± 1.22 μg mL) than the standard ascorbic acid. Oral bioavailability and toxicological parameters were considered, and most of the compounds satisfied Lipinski's rule of five and Veber's rule, except for one violation by a few derivatives. Molecular docking and molecular dynamics simulation were performed, providing more explicit ideas on the binding interaction and stability of compounds that exhibited wet lab activity. Average RMSD and RMSF values ranged between 0.5 Å and 2.5 Å, which indicated the stability of ligands inside the complex, yielding some engrossing insights.