Medicinal Chemistry Research

, Volume 27, Issue 2, pp 520–530 | Cite as

Design, synthesis and biological evaluation of 2-Phenyl-4H-chromen-4-one derivatives as polyfunctional compounds against Alzheimer’s disease

  • Manjinder Singh
  • Maninder Kaur
  • Bhawna Vyas
  • Om Silakari
Original Research
  • 93 Downloads

Abstract

Polyfunctional compounds comprise a novel class of therapeutic agents for the treatment of multi-factorial diseases. A series of 2-Phenyl-4H-chromen-4-one and its derivatives (5an) were designed, synthesized, and evaluated for their poly-functionality against acetylcholinestrase (AChE) and advanced glycation end products (AGEs) formation inhibitors against Alzheimer’s disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit AChE AGEs formation with additional radical scavenging activity. Especially, 5m, 5b, and 5j displayed the greatest ability to inhibit AChE (IC50 = 8.0, 8.2, and 11.8 nM, respectively) and AGEs formation (IC50 = 55, 79, and 54 µM, respectively) with good antioxidant activity. Molecular docking studies explored the detailed interaction pattern with active, peripheral, and mid-gorge sites of AChE. These compounds, exhibiting such multiple pharmacological activities, can be further taken a lead for the development of potent drugs for the treatment of Alzheimer’s disease.

Keywords

AChE inhibitor Alzheimer’s disease Antioxidants Flavonoids AGEs Flavone 

Abbreviations

ChE

Cholinesterase

AD

Alzheimer’s disease

AChE

Acetylcholinesterase

AGEs

Advanced glycation end products

CAS

Catalytic active site

PAS

Peripheral anionic site

ACh

Acetylcholine

FDA

Food and drug administration

OS

Oxidative stress

ROS

Reactive oxygen species

β-amyloid

RAGE

Receptor for AGEs

DPPH

1,1-diphenyl-2-picryl-hydrazyl

EWG

Electron withdrawing groups

Notes

Acknowledgements

We acknowledge the financial support from the “Indian Council of Medical Research (ICMR)”, New Delhi, for providing us Senior Research Fellowships (ICMR-SRF); Award nos. BIC/11(11)/2014 and BIC/11(02)/2013.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_2078_MOESM1_ESM.docx (639 kb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Manjinder Singh
    • 1
  • Maninder Kaur
    • 1
  • Bhawna Vyas
    • 2
  • Om Silakari
    • 1
  1. 1.Molecular Modeling Lab, Department of Pharmaceutical Sciences and Drug ResearchPunjabi UniversityPatialaIndia
  2. 2.Department of ChemistryPunjabi UniversityPatialaIndia

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