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Bioorg Chem. 2015 Aug;61:7-12. doi: 10.1016/j.bioorg.2015.05.005. Epub 2015 May 21.

Discovery of isoalloxazine derivatives as a new class of potential anti-Alzheimer agents and their synthesis.

Author information

1
Pharmacy Department, Faculty of Technology & Engineering, The M. S. University of Baroda, Vadodara 390001, Gujarat, India.
2
Division of Neurobiology, Department of Zoology, Faculty of Science, The M. S. University of Baroda, Vadodara 390001, Gujarat, India.
3
Pharmacy Department, Faculty of Technology & Engineering, The M. S. University of Baroda, Vadodara 390001, Gujarat, India. Electronic address: mryadav11@yahoo.co.in.

Abstract

This article describes discovery of a novel and new class of cholinesterase inhibitors as potential therapeutics for Alzheimer's disease. A series of novel isoalloxazine derivatives were synthesized and biologically evaluated for their potential inhibitory outcome for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds exhibited high activity against both the enzymes AChE as well as BuChE. Of the synthesized compounds, the most potent isoalloxazine derivatives (7m and 7q) showed IC50 values of 4.72 μM and 5.22 μM respectively against AChE; and, 6.98 μM and 5.29 μM respectively against BuChE. These two compounds were further evaluated for their anti-aggregatory activity for β-amyloid (Aβ) in presence and absence of AChE by performing Thioflavin-T (ThT) assay and Congo red (CR) binding assay. In order to evaluate cytotoxic profile of these two potential compounds, cell viability assay of SH-SY5Y human neuroblastoma cells was performed. Further, to understand the binding behavior of these two compounds with AChE and BuChE enzymes, docking studies have been reported.

KEYWORDS:

Alzheimer’s disease; Cholinesterase’s inhibition; Cytotoxicity; Isoalloxazine; β-Amyloid

PMID:
26042530
DOI:
10.1016/j.bioorg.2015.05.005
[Indexed for MEDLINE]

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