Microwave-assisted synthesis, biological assessment, and molecular modeling of aza-heterocycles: Potential inhibitory capacity of cholinergic enzymes to Alzheimer's disease

Efraín Polo, Luis Prent-Peñaloza, Yeray A.Rodríguez Núñez, Lady Valdés-Salas, Jorge Trilleras, Juan Ramos, José A. Henao, Antonio Galdámez, Alejandro Morales-Bayuelo, Margarita Gutiérrez

Research output: Contribution to journalArticlepeer-review

Abstract

A highly regioselective solvent-free microwave-assisted synthesis of pyrazoles and tetrahydroindazoles based on the condensation of 1,3-diketones with arylhydrazines is described. Compounds were evaluated as cholinesterase inhibitors in order to identify an alternative treatment for Alzheimer's disease. All compounds displayed moderated acetylcholinesterase inhibitory activity and most of the compounds displayed remarkable butyrylcholinesterase inhibitory activity and selectivity. The compounds 3y and 3i with IC50 of 1.65 and 3.59 µM, respectively, were the most active and selective compounds as butyrylcholinesterase inhibitors. Likewise, the compounds were tested as antioxidants agents, results showed that they have the ability to trap free-radicals. Molecular Docking studies showed a key π-π stacking interaction of most of the compounds with residue Trp82 within of butyrylcholinesterase active site. Molecular quantum similarity field, global and local reactivity descriptors, and the Fukui functions were calculated in the Density Functional Theory framework to analyze the reactivity patterns along with the molecular set.

Original languageEnglish
Article number129307
JournalJournal of Molecular Structure
Volume1224
DOIs
Publication statusPublished - 15 Jan 2021

Keywords

  • Alzheimer Disease
  • Cholinergic enzymes
  • Crystal structure
  • Molecular docking
  • Pyrazole
  • Tetrahydroindazole

ASJC Scopus subject areas

  • Analytical Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Inorganic Chemistry

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