Synthesis, molecular docking and enzyme inhibitory approaches of some new chalcones engrafted pyrazole as potential antialzheimer, antidiabetic and antioxidant agents.

• A new series of chalcones based pyrazole were designed and synthesized. • Compounds 5a, 5l and 5w were assigned their chemical structures by X-ray diffraction analysis. • Some compounds exhibited in vitro anti-acetylcholinesterase potential, antidiabetic potential against α-glucosidase and α-amylase, and antioxidant potentials against DPPH free radicals. About 25 chalcones engrafted pyrazole scaffold combined with benzothiophene and indole moieties 5a-y were designed and constructed in two steps using readily available acetyl acetone, phenyl hydrazine and DMF-DMA as starting material. The synthesized chalcone analogs were screened for in vitro anti-acetylcholinesterase potential, antidiabetic potential against α -glucosidase and α -amylase, and antioxidant potentials against DPPH free radicals. The compounds 5a, 5r, 5m, 5o and 5p showed strongest acetylcholine esterase inhibition (AChEI) with IC 50 values of 5 ± 1.16 μg/mL (5p), 8 ± 0.14 μg/mL (5a), 8 ± 0.57 μg/mL (5r), 10 ± 1.73 μg/mL (5m) and 10 ± 0.60 μg/mL (5o). The highest inhibition against α -glucosidase was demonstrated by compounds 5f, 5o, 5j, 5e, 5c, and 5a with IC 50 values of 4 ± 0.14, 6 ± 0.43, 8 ± 0.43, 10 ± 0.11, 11 ± 0.28 and 12 ± 0.57 μg/mL respectively, whereas, the compounds 5x, 5d, 5w, 5y and 5u showed prominent α-amylase inhibition with IC 50 values of 20 ± 1.15 μg/mL (5x), 30 ± 0.60 μg/mL (5d), 40 ± 0.72 μg/mL (5w), 40 ± 0.50 μg/mL (5y), and 60 ± 2.19 μg/mL (5u). The highest anti-oxidant potential against DPPH free radicals was demonstrated by compounds 5w, 5v and 5y with IC 50 values of 160 ± 5.77, 260 ± 4.63, and 360 ± 4.04 μg/mL respectively. Molecular docking was used to study their interaction with the active site of enzymes. [ABSTRACT FROM AUTHOR]