New 3- O -substituted xanthone derivatives as promising acetylcholinesterase inhibitors.

Tytuł:: New 3- O -substituted xanthone derivatives as promising acetylcholinesterase inhibitors.
Autorzy:: Loh ZH; School of Biosciences, Taylor's University, Lakeside Campus, Subang Jaya, Malaysia.
Kwong HC; School of Chemical Sciences, Universiti Sains Malaysia, George Town, Malaysia.
Lam KW; Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Teh SS; Energy and Environment Unit, Engineering and Processing Division, Malaysian Palm Oil Board, Bandar Baru Bangi, Malaysia.
Ee GCL; Department of Chemistry, Faculty of Science, University Putra Malaysia, Serdang, Malaysia.
Quah CK; X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, George Town, Malaysia.
Ho ASH; School of Biosciences, Taylor's University, Lakeside Campus, Subang Jaya, Malaysia.
Mah SH; School of Biosciences, Taylor's University, Lakeside Campus, Subang Jaya, Malaysia.; Centre for Drug Discovery and Molecular Pharmacology, Faculty of Health and Medical Sciences, Taylor's University, Lakeside Campus.
Źródło:: Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2021 Dec; Vol. 36 (1), pp. 627-639.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: Basingstoke, UK : Taylor & Francis, c2002-
MeSH Terms:: Acetylcholinesterase/*metabolism
Butyrylcholinesterase/*metabolism
Cholinesterase Inhibitors/*pharmacology
Xanthones/*pharmacology
Animals ; Cholinesterase Inhibitors/chemical synthesis ; Cholinesterase Inhibitors/chemistry ; Crystallography, X-Ray ; Dose-Response Relationship, Drug ; Electrophorus ; Horses ; Models, Molecular ; Molecular Structure ; Structure-Activity Relationship ; Xanthones/chemical synthesis ; Xanthones/chemistry
References:: Curr Med Chem. 2005;12(21):2517-38. (PMID: 16250875)
Biochem J. 2013 Aug 1;453(3):393-9. (PMID: 23679855)
Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9031-5. (PMID: 8415649)
Bioorg Med Chem. 2016 Sep 15;24(18):4263-4271. (PMID: 27448774)
Pharm Biol. 2014 Jul;52(7):898-903. (PMID: 24621306)
Chem Biodivers. 2004 Jun;1(6):819-29. (PMID: 17191882)
Molecules. 2012 May 21;17(5):6071-82. (PMID: 22614861)
Planta Med. 2004 Oct;70(10):1011-4. (PMID: 15490334)
Molecules. 2015 Jun 19;20(6):11387-99. (PMID: 26102071)
Molecules. 2012 Aug 24;17(9):10142-58. (PMID: 22922284)
Chem Cent J. 2013 Apr 27;7(1):78. (PMID: 23622085)
J Comput Aided Mol Des. 1996 Oct;10(5):427-40. (PMID: 8951652)
Bioorg Med Chem. 2002 Dec;10(12):3725-30. (PMID: 12413829)
Dialogues Clin Neurosci. 2000 Jun;2(2):111-28. (PMID: 22033801)
Med Chem. 2012 Nov;8(6):1012-25. (PMID: 22779801)
Fitoterapia. 2020 Oct;146:104637. (PMID: 32470371)
Chem Biol Interact. 2009 Oct 30;181(3):383-9. (PMID: 19596285)
Nat Prod Res. 2009;23(6):539-45. (PMID: 19384730)
J Mol Neurosci. 2006;30(1-2):219-22. (PMID: 17192680)
J Adv Pharm Technol Res. 2012 Oct;3(4):200-1. (PMID: 23378939)
Bioorg Med Chem Lett. 2007 Dec 1;17(23):6421-4. (PMID: 17950599)
Bioorg Med Chem. 2007 Jan 1;15(1):575-85. (PMID: 17008100)
J Med Chem. 2012 Nov 26;55(22):10282-6. (PMID: 23035744)
Bioorg Med Chem. 2017 Feb 15;25(4):1471-1480. (PMID: 28126439)
Carbohydr Res. 2020 May;491:107977. (PMID: 32169593)
ACS Chem Neurosci. 2019 Jan 16;10(1):155-167. (PMID: 30372021)
Drug Saf. 1998 Dec;19(6):465-80. (PMID: 9880090)
Bioorg Chem. 2019 Mar;83:277-288. (PMID: 30391700)
Bioorg Med Chem Lett. 2019 Dec 15;29(24):126754. (PMID: 31708262)
Theranostics. 2018 Feb 5;8(6):1481-1493. (PMID: 29556336)
Pharmacotherapy. 2000 Jan;20(1):1-12. (PMID: 10641971)
Prog Neurobiol. 1998 May;55(1):59-77. (PMID: 9602500)
Bioorg Med Chem Lett. 2014 May 1;24(9):2062-5. (PMID: 24717154)
Acta Neurobiol Exp (Wars). 2004;64(1):99-105. (PMID: 15190684)
Acta Crystallogr A Found Adv. 2015 Jan;71(Pt 1):3-8. (PMID: 25537383)
Mediators Inflamm. 2015;2015:350564. (PMID: 26538826)
Eur Neurol. 2002;47(1):64-70. (PMID: 11803198)
Fitoterapia. 2013 Dec;91:140-147. (PMID: 24007984)
Eur J Med Chem. 2016 Jun 30;116:267-280. (PMID: 27111599)
Biochem Pharmacol. 1961 Jul;7:88-95. (PMID: 13726518)
Bioorg Med Chem Lett. 2016 Nov 15;26(22):5387-5394. (PMID: 27789142)
J Nutr. 2010 Apr;140(4):842-7. (PMID: 20181789)
Eur J Med Chem. 2016 Jun 10;115:381-92. (PMID: 27031214)
Chem Biol Interact. 2019 Aug 1;308:216-223. (PMID: 31150627)
Chem Biol Drug Des. 2015 Nov;86(5):1215-20. (PMID: 26010139)
BMC Neurol. 2009 Jun 12;9 Suppl 1:S3. (PMID: 19534732)
Phytomedicine. 2014 Sep 25;21(11):1303-9. (PMID: 25172794)
Expert Rev Neurother. 2008 Jan;8(1):9-17. (PMID: 18088197)
Acta Crystallogr A. 2008 Jan;64(Pt 1):112-22. (PMID: 18156677)
Bioorg Med Chem. 2017 Mar 15;25(6):1997-2009. (PMID: 28237559)
J Nat Prod. 2008 May;71(5):895-7. (PMID: 18336006)
Arch Pharm Res. 2010 Oct;33(10):1539-56. (PMID: 21052932)
Food Chem Toxicol. 2008 Feb;46(2):688-93. (PMID: 18029076)
Contributed Indexing:: Keywords: Alzheimer’s disease; enzyme kinetic study; molecular docking; structure–activity relationship study; synthesis
Substance Nomenclature:: 0 (Cholinesterase Inhibitors)
0 (Xanthones)
9749WEV0CA (xanthone)
EC 3.1.1.7 (Acetylcholinesterase)
EC 3.1.1.8 (Butyrylcholinesterase)
Entry Date(s):: Date Created: 20210209 Date Completed: 20210615 Latest Revision: 20220118
Update Code:: 20240104
PubMed Central ID:: PMC8759733
DOI:: 10.1080/14756366.2021.1882452
PMID:: 33557647
: Czasopismo naukowe

Pełny tekst

A new series of 3- O -substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of them ( 5 , 8 , 11 , 17 , 19 , 21 - 23 , 26 - 28 ) exhibited significant effects with the IC 50 values ranged 0.88 to 1.28 µM. The AChE enzyme kinetic study of 3-(4-phenylbutoxy)-9 H -xanthen-9-one ( 23 ) and ethyl 2-((9-oxo-9 H -xanthen-3-yl)oxy)acetate ( 28 ) showed a mixed inhibition mechanism. Molecular docking study showed that 23 binds to the active site of AChE and interacts via extensive π-π stacking with the indole and phenol side chains of Trp86 and Tyr337, besides the hydrogen bonding with the hydration site and π-π interaction with the phenol side chain of Y72. This study revealed that 3- O -alkoxyl substituted xanthone derivatives are potential lead structures, especially 23 and 28 which can be further developed into potent AChE inhibitors.

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