Umar_2019_Eur.J.Med.Chem_175_2

2-(piperazin-1-yl)N-(1H-pyrazolo[3,4-b]pyridin-3-yl)acetamides are described as a new class of selective and potent acetylcholinesterase (AChE) inhibitors and amyloid beta aggregation inhibitors. Formation of synthesized compounds (P1P9) was justified via H(1) NMR, C(13) NMR, mass spectra and single crystal X-Ray diffraction study. All compounds were evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activity, inhibition of self-mediated Abeta aggregation and Cu(II)-mediated Abeta aggregation. Also, docking study carried out was in concordance with in vitro results. The most potent molecule amongst the derivatives exhibited excellent anti-AChE activity (IC50=4.8nM). Kinetic study of P3 suggested it to be a mixed type inhibitor. In vitro study revealed that all the compounds are capable of inhibiting self-induced beta-amyloid (Abeta) aggregation with the highest inhibition percentage to be 81.65%. Potency of P1 and P3 to inhibit self-induced Abeta1-42 aggregation was ascertained by TEM analysis. Compounds were also evaluated for their Abeta disaggregation, antioxidation, metal-chelation activity.