Design, synthesis and biological evaluation of 2-Phenyl-4H-chromen-4-one derivatives as polyfunctional compounds against Alzheimer’s disease
- 93 Downloads
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 (5a–n) 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.
KeywordsAChE inhibitor Alzheimer’s disease Antioxidants Flavonoids AGEs Flavone
Advanced glycation end products
Catalytic active site
Peripheral anionic site
Food and drug administration
Reactive oxygen species
Receptor for AGEs
Electron withdrawing groups
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.
- Cabrera M, Simoens M, Falchi G, Lavaggi ML, Piro OE, Castellano EE, Vidal A, Azqueta A, Monge A, de Ceráin AL, Sagrera G, Seoane G, Cerecetto H, González M (2007) Synthetic chalcones, flavanones, and flavones as antitumoral agents: biological evaluation and structure–activity relationships. Bioorg Med Chem 15:3356–3367CrossRefPubMedGoogle Scholar
- Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, Repasky MP, Knoll EH, Shelley M, Perry JK, Shaw DE, Francis P, Shenkin PS (2004) Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47:1739–1749CrossRefPubMedGoogle Scholar
- Glide (2010) Version 5.6. Schrodinger LLC, New YorkGoogle Scholar
- Ligprep (2011) Version 2.5. Schrodinger LLC, New YorkGoogle Scholar
- Lim SS, Han SM, Kim SY, Bae YS, Kang IJ (2007) Isolation of acetylcholinesterase inhibitors from the flowers of chrysanthemum indicum linne. Food Sci Biotech 16:265–269Google Scholar
- Pi RB, Ye MZ, Cheng ZY, Liu PQ (2008) Univ Zhongshan (UZHO-C). Patent CN101284812-A, ChinaGoogle Scholar
- Zhu JT, Choi RC, Chu GK, Cheung AW, Gao QT, Li J, Jiang ZY, Dong TT, Tsim KW (2007) Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells: a comparison of different flavonoids in activating estrogenic effect and in preventing beta-amyloid-induced cell death. J Agric Food Chem 55:2438–2445CrossRefPubMedGoogle Scholar