A multifunctional therapeutic approach: Synthesis, biological evaluation, crystal structure and molecular docking of diversified 1H-pyrazolo[3,4-b]pyr...

ID: ALA4393694

Journal: Eur J Med Chem

Title: A multifunctional therapeutic approach: Synthesis, biological evaluation, crystal structure and molecular docking of diversified 1H-pyrazolo[3,4-b]pyridine derivatives against Alzheimer's disease.

Authors: Umar T, Shalini S, Raza MK, Gusain S, Kumar J, Seth P, Tiwari M, Hoda N.

Abstract: 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 β aggregation inhibitors. Formation of synthesized compounds (P1P9) was justified via H¹ NMR, C¹³ 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 Aβ aggregation and Cu(II)-mediated Aβ 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 = 4.8 nM). 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 β-amyloid (Aβ) aggregation with the highest inhibition percentage to be 81.65%. Potency of P1 and P3 to inhibit self-induced Aβ_1-42 aggregation was ascertained by TEM analysis. Compounds were also evaluated for their Aβ disaggregation, antioxidation, metal-chelation activity.

CiteXplore: 31055149

DOI: 10.1016/j.ejmech.2019.04.038

Patent ID: ┄