Novel Carbazole-Thiazole-Schiff Base Hybrids: Design, Synthesis, Antimicrobial, Antioxidant, Molecular Docking and Dynamics Studies
摘要
Eleven novel carbazole-thiazole-Schiff base derivatives (2a-2k) were synthesized following a two-step reaction methodology. Various Spectroscopic methods clarified the structures of these new entities. In vitro antimicrobial activity was assessed using the agar disc diffusion method, where compounds 2a, 2f, 2g and 2h demonstrated high antimicrobial potency against most bacterial strains. Compound 2a showed a maximum inhibitory value against B. megaterium (20.2 ± 0.6 mm), 2h against the rest of the three gram-positive bacterial strains, and 2f against the two gram-negative bacterial strains. Besides, the antioxidant activity of the synthesized compounds was determined by DPPH free radical assay, where most of the new molecules had a moderate to lower IC50 value and compound 2i showed the most potent antioxidant capability with the minimum IC50 values of 41.75 ± 0.54 µg/mL compared to standard ascorbic acid (49.68 ± 3.68 µg/mL). Based on the wet lab activity, compounds 2f, 2h, 2k, and 2i were studied further for their theoretical basis through molecular docking and dynamics simulation. The 2h-5JBO complex exerted the most stability among the four complexes and displayed enhanced binding interactions. In ADMET prediction, all compounds adhered to the standard range, especially compound 2a, and no adverse effects were found for any derivatives.
Graphical Abstract