دورية أكاديمية
أعرض في EDS

Synthesis, Crystal Structure, and Biological Evaluation of Fused Thiazolo[3,2- a ]Pyrimidines as New Acetylcholinesterase Inhibitors.

التفاصيل البيبلوغرافية
العنوان: Synthesis, Crystal Structure, and Biological Evaluation of Fused Thiazolo[3,2- a ]Pyrimidines as New Acetylcholinesterase Inhibitors.
المؤلفون: Mahgoub MY; Chemistry Department, Faculty of Science, South Valley University, Qena 83523, Egypt. m.mahgoub2013@gmail.com.; Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal. m.mahgoub2013@gmail.com., Elmaghraby AM; Chemistry Department, Faculty of Science, South Valley University, Qena 83523, Egypt. awatef_elmaghraby@yahoo.com., Harb AA; Chemistry Department, Faculty of Science, South Valley University, Qena 83523, Egypt. alifaragharb@gmail.com., Ferreira da Silva JL; Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal. joao.luis@tecnico.ulisboa.pt., Justino GC; Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal. goncalo.justino@tecnico.ulisboa.pt., Marques MM; Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal. matilde.marques@tecnico.ulisboa.pt.
المصدر: Molecules (Basel, Switzerland) [Molecules] 2019 Jun 21; Vol. 24 (12). Date of Electronic Publication: 2019 Jun 21.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, c1995-
مواضيع طبية MeSH: Acetylcholinesterase/*chemistry , Cholinesterase Inhibitors/*chemical synthesis , Pyrimidines/*chemical synthesis, Acetylcholinesterase/drug effects ; Cholinesterase Inhibitors/chemistry ; Crystallography, X-Ray ; Humans ; Molecular Docking Simulation ; Pyrimidines/chemistry ; Tandem Mass Spectrometry
مستخلص: A new series of thiazolo[3,2- a ]pyrimidine bromide salt derivatives 7a - d were synthesized from 3,4-dihydropyrimidinethione precursors. The target compounds were fully characterized by 1D- and 2D-NMR, high resolution ESI-MS/MS and single crystal X-ray diffraction analysis, which confirmed a regioselective 5 H cyclization of the dihydropyrimidinethiones. All target compounds were evaluated in vitro as human acetylcholinesterase ( h AChE) inhibitors via an Ellman-based colorimetric assay and showed good inhibition activities (better than 70% at 10 µM and IC 50 values in the 1 µM range). Molecular docking simulations for all target products into h AChE were performed and confirmed strong binding to the enzyme. These results provide a promising and new starting point to improve acetylcholinesterase inhibitors and explore novel treatment options against Alzheimer's disease.
References: J Neurol Neurosurg Psychiatry. 1999 Feb;66(2):137-47. (PMID: 10071091)
Am J Psychiatry. 1999 Jul;156(7):1029-34. (PMID: 10401447)
Mol Psychiatry. 2000 Nov;5(6):673-7. (PMID: 11126398)
Arch Pharm (Weinheim). 2000 Dec;333(12):415-20. (PMID: 11199471)
Methods Find Exp Clin Pharmacol. 2000 Oct;22(8):609-13. (PMID: 11256231)
Mini Rev Med Chem. 2001 Sep;1(3):267-72. (PMID: 12369973)
EMBO J. 2003 Jan 2;22(1):1-12. (PMID: 12505979)
Biochem Pharmacol. 1961 Jul;7:88-95. (PMID: 13726518)
J Comput Chem. 2004 Oct;25(13):1605-12. (PMID: 15264254)
Acta Crystallogr B. 2004 Dec;60(Pt 6):627-68. (PMID: 15534375)
J Pharmacol Exp Ther. 2005 Dec;315(3):1346-53. (PMID: 16144975)
EMBO J. 2006 Jun 21;25(12):2746-56. (PMID: 16763558)
Chem Commun (Camb). 2007 Oct 7;(37):3814-6. (PMID: 18217656)
Acta Crystallogr D Biol Crystallogr. 2009 Feb;65(Pt 2):148-55. (PMID: 19171970)
ChemMedChem. 2009 Apr;4(4):633-48. (PMID: 19212959)
J Comput Chem. 2010 Jan 30;31(2):455-61. (PMID: 19499576)
J Enzyme Inhib Med Chem. 2010 Oct;25(5):615-21. (PMID: 20001274)
Eur J Med Chem. 2010 Apr;45(4):1494-501. (PMID: 20110135)
ChemMedChem. 2010 Jul 5;5(7):1092-101. (PMID: 20480490)
Eur J Med Chem. 2011 Mar;46(3):819-24. (PMID: 21255878)
Antiviral Res. 2012 Aug;95(2):118-27. (PMID: 22659095)
Eur J Med Chem. 2012 Sep;55:195-204. (PMID: 22871486)
ISRN Org Chem. 2013 Aug 18;2013:706437. (PMID: 24052868)
ACS Med Chem Lett. 2013 Sep 23;4(11):1091-6. (PMID: 24900610)
Bioorg Med Chem Lett. 2014 Sep 1;24(17):4239-42. (PMID: 25096298)
Bioorg Med Chem. 2014 Sep 1;22(17):4553-65. (PMID: 25131958)
Eur J Med Chem. 2014 Nov 24;87:500-7. (PMID: 25282671)
Acta Crystallogr A Found Adv. 2015 Jan;71(Pt 1):3-8. (PMID: 25537383)
Acta Crystallogr C Struct Chem. 2015 Jan;71(Pt 1):3-8. (PMID: 25567568)
J Appl Crystallogr. 2015 Jan 30;48(Pt 1):3-10. (PMID: 26089746)
Saudi Pharm J. 2016 Mar;24(2):119-32. (PMID: 27013904)
ChemMedChem. 2017 Jul 6;12(13):1022-1032. (PMID: 28503918)
Bioorg Chem. 2017 Oct;74:41-52. (PMID: 28750204)
معلومات مُعتمدة: UID/QUI/00100/2013, UID/QUI/100/2019, SAICTPAC/0019/2015, and PTDC/QUI-QAN/32242/2017 Fundação para a Ciência e a Tecnologia (FCT, Portugal)
فهرسة مساهمة: Keywords: acetylcholinesterase inhibition; crystal structures; molecular docking; thiazolopyrimidines
المشرفين على المادة: 0 (Cholinesterase Inhibitors)
0 (Pyrimidines)
EC 3.1.1.7 (Acetylcholinesterase)
تواريخ الأحداث: Date Created: 20190626 Date Completed: 20191203 Latest Revision: 20200225
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6630738
DOI: 10.3390/molecules24122306
PMID: 31234400
قاعدة البيانات: MEDLINE
الوصف
تدمد:1420-3049
DOI:10.3390/molecules24122306