Synthesis, molecular modeling and BACE-1 inhibitory study of tetrahydrobenzo[b] pyran derivatives

Bhaskar, Vijaya K (2019) Synthesis, molecular modeling and BACE-1 inhibitory study of tetrahydrobenzo[b] pyran derivatives. Bioorganic Chemistry, 84. pp. 202-210. ISSN 0045-2068

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Abstract

β-Secretase (BACE1) has been broadly documented as one of the possible therapeutic targets for the treatment of Alzheimer’s disease. In this paper, we report the synthesis and the for β-secretase (BACE-1) inhibitory activity of new series of tetrahydrobenzo [b] pyran derivatives. One-pot synthesis of tetrahydrobenzo [b] pyrans was carried out by condensing aromatic aldehyde, malononitrile and 1,3- yclohexanedione using ionic liquid 1- butyl-3-methyl imidazolium chloride ([bmIm]Cl−) in aqueous alcohol media. The addition of alcohol and water in the ratio of 1:2 keeps all the reactants in solution which facilitates the reaction and makes the product formation very easy. The synthesized compounds were subjected to BACE1 inhibition assay and six compounds,4d, 4e, 4f, 4h, 4i, and 4p have shown significant IC50 values at micromolar level. Among these six active compounds, 4e was a potential inhibitor with its IC50 value in nanomolar range. All the synthesized compounds were docked onto the active site of β-Secretase enzyme.

Item Type: Article
Uncontrolled Keywords: Tetrahydrobenzo [b] pyrans; Ionic liquid; 1-Butyl-3-imidazolium chloride; β-secretase; Surflex dock; Molecular docking
Subjects: Pharmacy > MCOPS Manipal > Pharmaceutical Chemistry
Depositing User: KMC Library
Date Deposited: 11 Apr 2019 06:47
Last Modified: 11 Apr 2019 06:47
URI: http://eprints.manipal.edu/id/eprint/153632

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