Exploration of synthetic antioxidant flavonoid analogs as acetylcholinesterase inhibitors: an approach towards finding their quantitative structure–activity relationship
- 46 Downloads
The binding interactions between acetylcholinesterase (AChE) and a series of antioxidant flavonoid analogs were studied by fluorescence spectroscopic assay. The present study incorporated different classes of naturally occurring and synthetic flavonoid compounds like flavones, isoflavones, and chalcones as well as a few standard antioxidants. The AChE inhibitory (AChEI) activity of these compounds was further analyzed using in silico techniques, namely pharmacophore mapping, quantitative structure–activity relationship (QSAR) analysis, and molecular docking studies. We have also compared the AChE inhibitory and radical scavenging antioxidant activities of these compounds. Both the AChE inhibitory and antioxidant activities of these compounds were found to be highly dependent on their structural patterns. However, it was observed that, in general, flavones are comparatively better AChE inhibitors as well as antioxidants compared to chalcones.
KeywordsFlavonoids Acetylcholinesterase inhibitory activity Antioxidant QSAR In silico method
The authors thank the SERB-DST [Sanction Order No. SR/SO/BB-0007/2011 dated 21.08.2012 to NAB]. AK and TM thank UGC-CSIR (NET) and UGC-MANF, respectively for their fellowships. The authors thank the Department of Chemistry, Visva-Bharati and its DST-FIST and UGC-SAP (Phase-II) programs for necessary infrastructural and instrumental facilities.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Balkis A, Tran K, Lee YZ, Ng K (2015) Screening flavonoids for inhibition of acetylcholinesterase identified baicaleien as the most potent inhibitor. J Agric Sci 7:26–35Google Scholar
- Cerius2 Version 410 (2005) Accelrys, Inc., San Diego, CAGoogle Scholar
- ChemAxon Marvin Sketch 5115, Budapest, Hungary, http://www.chemaxon.com/products.html
- Chigurupati S, Selvaraj M, Mani V, Mohammad JI, Selvarajan KK, Akhtar SS, Marikannan M, Raj S, Teh LK, Salleh MZ (2018) Synthesis of azomethines derived from cinnamaldehyde and vanillin: in vitro aetylcholinesterase inhibitory, antioxidant and insilico molecular docking studies. Med Chem Res 27:807–816CrossRefGoogle Scholar
- Dhoubhadel SP, Tuladhar SM, Tuladhar SM, Wagley PP (1981) Synthesis of some 3-methoxyflavones and chromones. Ind J Chem 20:511–512Google Scholar
- Discovery Studio (2007) Version 2.5. Accelrys Software, San Diego, CA, USAGoogle Scholar
- Furniss BS, Hannaford AJ, Rogers V, Smith PWG, Tatchell AR (1984) Vogel’s text book of practical organic chemistry, 4th edn. John Wiley & Sons, New YorkGoogle Scholar
- Geissman TA (ed) (1962) The chemistry of flavonoid compounds. Pergamon Press, OxfordGoogle Scholar
- Jeong JM, Kang SK, Lee IH, Lee JY, Jung H, Choi CH (2007) Antioxidant and chemosensitizing effects of flavonoids with hydroxyl and/or methoxy groups and structure–activity relationship. J Pharm Sci 10:537–546Google Scholar
- Mauri A, Consonni V, Pavan M, Todeschini R (2006) Dragon software: an easy approach to molecular descriptor calculations. Match 56:237–248Google Scholar
- Naik KN, Naik HB (1990) Synthesis of some chalcones and their antibacterial activity. J Ind Chem Soc 67:844–845Google Scholar
- Reyes AE, Chacón MA, Dinamarca MC, Cerpa W, Morgan C, Inestrosa NC (2004) Acetylcholinesterase-a complexes are more toxic than a fibrils in rat hippocampus: effect on rat-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss. Am J Pathol 164:2163–2174CrossRefGoogle Scholar