2-Arylbenzofurans from Artocarpus lakoocha and methyl ether analogs with potent cholinesterase inhibitory activity

  • Eur J Med Chem. 2018 Jan 1:143:1301-1311. doi: 10.1016/j.ejmech.2017.10.019.
Umalee Namdaung  1 ,  Anan Athipornchai  2 ,  Thongchai Khammee  3 ,  Mayuso Kuno  4 ,  Sunit Suksamrarn  5
Affiliations
  • 1. Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand; Center of Excellence for Innovation in Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
  • 2. Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Burapha University, Chon-Buri 20131, Thailand.
  • 3. Department of Chemistry, Faculty of Science and Technology, Phranakhon Rajabhat University, Bangkok 10220, Thailand.
  • 4. Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
  • 5. Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand; Center of Excellence for Innovation in Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand. Electronic address: [email protected].
PMID: 29126732 DOI: 10.1016/j.ejmech.2017.10.019
Abstract

In vitro screening for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of the Artocarpus lakoocha root-bark extracts revealed interesting results. Bioassay-guided fractionation resulted in the isolation of two new (1 and 2) and six known 2-arylbenzofurans 3-8, along with one stilbenoid 9 and one flavonoid 10. The structures of the isolated compounds were elucidated by UV, IR, 1D- and 2D-NMR and MS spectroscopic data analysis. Compounds 4, 6 and 7 exhibited more potent AChE inhibitory activity (IC50 = 0.87-1.10 μM) than the reference drug, galantamine. Compounds 4, 8 and 9 displayed greater BChE inhibition than the standard drug. The preferential inhibition of BChE over AChE indicated that 4 also showed a promising dual AChE and BChE Inhibitor. The synthetic mono-methylated analogs 4a-c and 6a-b were found to be good BChE inhibitors with IC50 values ranging between 0.31 and 1.11 μM. Based on the docking studies, compounds 4 and 6 are well-fitted in the catalytic triad of AChE. Compounds 4 and 6 showed different binding orientations on BChE, and the most potent BChE Inhibitor 4 occupied dual binding to both CAS and PAS more efficiently.

Keywords
2-Arylbenzofuran; Alzheimer's disease; Anticholinesterase activity; Artocarpus lakoocha; Molecular docking.
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