Synthesis, Antimicrobial and Antioxidant Activity With ADMET Prediction, Molecular Docking, and Dynamics Studies of...

Eleven thiazole-Schiff base derivatives 2a-2k were synthesized via a two-step synthetic route and elucidated by spectral analyses (infrared [IR], ¹H NMR, ¹³C NMR, and HRMS). The in vitro antimicrobial activity of the synthesized thiazole derivatives was carried out against four gram-positive bacteria, two gram-negative bacteria, and two fungal strains. Compound 2b revealed the maximum antimicrobial potency against two bacterial strains, Staphylococcus aureus (25.9 ± 0.2) and Salmonella typhi (18.7 ± 0.6), compared to other compounds. Moreover, compound 2e showed an excellent zone of inhibition against Bacillus cereus (24.2 ± 1.3 mm), which is higher than standard ceftriaxone (20.2 ± 1.3 mm). The antioxidant capability of the synthesized analogs was investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. Compound 2g showed notable antioxidant potential with an IC₅₀ value of 27.74 ± 6.67 µg/mL, which was higher than the standard ascorbic acid (IC₅₀ = 49.68 ± 3.68 µg/mL). Compounds 2b, 2e, and 2g revealed moderate binding affinity with higher stability in molecular docking and dynamics simulation, except for complex 2b-2BV6. Additionally, absorption, distribution, metabolism, and excretion (ADME) properties and toxicological parameters were considered to understand the oral bioavailability of the derivatives, where the data were favorable for all except compound 2k.