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.
Eur J Med Chem
; 175: 2-19, 2019 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-31055149
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 ß 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 Aß aggregation and Cu(II)-mediated Aß 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 (IC50â¯=â¯4.8â¯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 ß-amyloid (Aß) aggregation with the highest inhibition percentage to be 81.65%. Potency of P1 and P3 to inhibit self-induced Aß1-42 aggregation was ascertained by TEM analysis. Compounds were also evaluated for their Aß disaggregation, antioxidation, metal-chelation activity.
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Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Piridinas
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Doença de Alzheimer
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Índia