Synthesis, characterization, and evaluation of pyrimidinone-linked thiazoles: DFT analysis, molecular docking,...

The paper describes the construction of a new series of pyrimidinone-linked thiazole derivatives through bromination of the initial Biginelli reaction product followed by the Hantzsch thiazole synthesis route. Various analytical techniques, including FT-IR, ¹H NMR, ¹³C NMR, and LCMS analysis, were employed to confirm the formation of the products. The synthesized compounds were primarily evaluated for their antibacterial activity, with a specific focus on their IC₅₀ values. Compound 4c demonstrated the most potent efficacy, displaying MIC and MBC values that varied from 0.23 to 0.71 mg/mL and 0.46-0.95 mg/mL, respectively. The anti-inflammatory potential was also observed in analogs 4a and 4c with marked activity in the 33.2-82.9 μM concentration range. Moreover, compounds 4a, and 4c demonstrated strong antioxidant effects, as reflected by their excellent IC₅₀ values of 38.6-43.5 μM respectively. DFT investigation showed that B. cereus was more susceptible, and E. coli was more resistant, with chloro-substituted compounds exhibiting potential reactivity. Some molecules with chloro-substituents showed promising results in density functional theory when compared to other substituents. In addition, the molecules underwent a corrosion study and demonstrated a high level of inhibition efficiency (4c) in comparison to other molecules. Further in silico studies of the synthesized thiazoles confirmed the good interactions with the target.