Synthesis, Biological Evaluation, in Silico ADMET Prediction, Molecular Docking and Dynamics Studies of...

A series of novel thiazole-Schiff base analogs (2a-2i) were synthesized through a multicomponent reaction involving thiosemicarbazide, 4-phenoxybenzaldehyde, and α-haloketone/phenacyl bromide derivatives. IR, ¹H NMR, and HRMS spectroscopic techniques characterized the newly synthesized derivatives. These compounds were subsequently employed for their antimicrobial and antioxidant activities using agar disc diffusion and DPPH free radical scavenging methods. The multi-faceted activity of compound 2c was revealed in both In Vitro experiments. It exhibited the highest potency against Bacillus subtilis (26.0 ± 1.0 mm) and Aspergillus niger (22.3 ± 0.6 mm) which exceeded the inhibitory value of standard ceftriaxone (20.7 ± 0.6 mm) and amphotericin B (8.7 ± 0.6 mm), respectively. Additionally, 2c demonstrated a remarkable sevenfold increase in antioxidant capability (IC₅₀ = 7.17 ± 2.61 µg/mL) compared to the standard ascorbic acid (IC₅₀ = 49.69 ± 19.18 µg/mL). The in silico ADMET prediction demonstrated that most synthesized compounds adhered to Lipinski's rule of five and Veber's rule, with 2i being the exception with one violation. Molecular docking studies and dynamics simulation were conducted to explore potential binding sites, interactions, and stability of the ligand-protein complexes, providing insights aligned with the In Vitro results.