Synthesis, quantum chemical, in vitro acetyl cholinesterase inhibition and molecular docking studies of four new coumarin based pyrazolylthiazole nuclei

Four new 3-(2-(3-Phenyl-5-substituted phenyl-4,5-dihydropyrazol-1-yl)thiazol-4-yl)-2H-chromen-2-one derivatives (1–4) were synthesized and fully characterized by spectroscopic techniques. The final structures of all chromenone analogues (1–4) were confirmed by single crystal X-ray diffraction analysis. Quantum chemical studies were performed to compare the results from the theoretical studies with the experimental (X-ray as well as spectroscopic) ones. The theoretically simulated geometric parameters and other spectroscopic properties agreed nicely with the experimental data. All compounds were evaluated for biological activity (acetyl cholinesterase inhibition potential). Compound 3 emerged as the most potent derivative in acetylcholine esterase (AChE) inhibition assay with IC50 = 27.29 μM. The IC50 of compound 3 is greater than the standard drug galantamine (IC50 = 44.02 μM). To rationalize the potencies, molecular docking studies were also carried out. These docking results revealed a good correlation between binding energies values and in vitro AChE inhibition assay.