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

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 alpha-glucosidase and alpha-amylase, and antioxidant potentials against DPPH free radicals. The compounds 5a, 5r, 5m, 5o and 5p showed strongest acetylcholine esterase inhibition (AChEI) with IC50 values of 5 +/- 1.16 mu g/mL (5p), 8 +/- 0.14 mu g/mL (5a), 8 +/- 0.57 mu g/mL (5r), 10 +/- 1.73 mu g/mL (5m) and 10 +/- 0.60 mu g/mL (5o). The highest inhibition against alpha-glucosidase was demonstrated by compounds 5f, 5o, 5j, 5e, 5c, and 5a with IC50 values of 4 +/- 0.14, 6 +/- 0.43, 8 +/- 0.43, 10 +/- 0.11, 11 +/- 0.28 and 12 +/- 0.57 mu g/mL respectively, whereas, the compounds 5x, 5d, 5w, 5y and 5u showed prominent alpha-amylase inhibition with IC50 values of 20 +/- 1.15 mu g/mL (5x), 30 +/- 0.60 mu g/mL (5d), 40 +/- 0.72 mu g/mL (5w), 40 +/- 0.50 mu g/mL (5y), and 60 +/- 2.19 mu g/mL (5u). The highest anti-oxidant potential against DPPH free radicals was demonstrated by compounds 5w, 5v and 5y with IC50 values of 160 +/- 5.77, 260 +/- 4.63, and 360 +/- 4.04 mu g/mL respectively. Molecular docking was used to study their interaction with the active site of enzymes. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

A series of compounds with chalcone scaffold combined with benzothiophene and indole moieties were designed and synthesized. These compounds were screened for their potential as anti-diabetic and antioxidant agents, and their interactions with enzymes were studied using molecular docking.