دورية أكاديمية
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Coumarin derivatives as inhibitors of d-amino acid oxidase and monoamine oxidase.

التفاصيل البيبلوغرافية
العنوان: Coumarin derivatives as inhibitors of d-amino acid oxidase and monoamine oxidase.
المؤلفون: Bester E; Pharmaceutical Chemistry, School of Pharmacy and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa. Electronic address: elizabethbesternwu@gmail.com., Petzer A; Pharmaceutical Chemistry, School of Pharmacy and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa. Electronic address: 12264954@nwu.ac.za., Petzer JP; Pharmaceutical Chemistry, School of Pharmacy and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa. Electronic address: jacques.petzer@nwu.ac.za.
المصدر: Bioorganic chemistry [Bioorg Chem] 2022 Jun; Vol. 123, pp. 105791. Date of Electronic Publication: 2022 Apr 06.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: New York, London, Academic Press.
مواضيع طبية MeSH: Monoamine Oxidase*/metabolism , Parkinson Disease*, Amino Acids ; Animals ; Coumarins/pharmacology ; Dose-Response Relationship, Drug ; Monoamine Oxidase Inhibitors/chemistry ; Monoamine Oxidase Inhibitors/pharmacology ; Receptors, N-Methyl-D-Aspartate ; Serine ; Structure-Activity Relationship ; Swine
مستخلص: d-Amino acid oxidase (DAAO) oxidises d-amino acids to ultimately produce the corresponding α-keto acids. The DAAO substrate, d-serine, is a co-agonist at NMDA receptors, while NMDA receptor hypo-function has been implicated in the pathophysiology of schizophrenia. Through the modulation of d-serine levels, the inhibition of DAAO represents a strategy to increase NMDA receptor function, and thus a potential treatment for schizophrenia. Literature reports that 3-hydroxycoumarin is a potent inhibitor of DAAO and represents an ideal lead for the development of novel DAAO inhibitors. Based on this, the present study investigated DAAO inhibition by a series of synthetic and commercially available coumarin derivatives. Due to structural similarity to coumarin, a synthetic series of 3,4-dihydroisoquinolin-1(2H)-one derivatives has also been included in this study. The results show that among 37 compound evaluated, four inhibit porcine kidney DAAO with IC 50  < 10 µM. The most potent inhibitors are 3,7-dihydroxycoumarin and 6,7-dihydroxycoumarin with an IC 50 values of 0.167 and 0.224 µM, respectively. These values are an improvement on that of the reference DAAO inhibitor, 3-methylpyrazole-5-carboxylic acid (IC 50  = 1.88 µM). Coumarin compounds are also known to inhibit the monoamine oxidase (MAO) enzymes, which are well established targets for the treatment of depression and Parkinson's disease. As DAAO and MAO are flavoenzymes, off-target inhibition may occur. The series were thus evaluated as potential MAO inhibitors, and a number of high potency inhibitors were identified. Seven compounds inhibit the recombinant human MAOs with IC 50  < 0.1 µM, with the most potent MAO-A and MAO-B inhibitors exhibiting IC 50 values of 0.033 and 0.012 µM, respectively. This is significantly more potent than the reference inhibitors, curcumin, isatin and toloxatone. This study concludes that active DAAO and MAO inhibitors may serve as novel leads for the design of compounds that may find future application in the treatment of neuropsychiatric (e.g. schizophrenia, depression) and neurodegenerative disorders (e.g. Parkinson's disease).
(Copyright © 2022 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Coumarin; D-amino acid oxidase; Depression; Monoamine oxidase; Parkinson’s disease; Schizophrenia
المشرفين على المادة: 0 (Amino Acids)
0 (Coumarins)
0 (Monoamine Oxidase Inhibitors)
0 (Receptors, N-Methyl-D-Aspartate)
452VLY9402 (Serine)
EC 1.4.3.4 (Monoamine Oxidase)
تواريخ الأحداث: Date Created: 20220412 Date Completed: 20220502 Latest Revision: 20220508
رمز التحديث: 20221213
DOI: 10.1016/j.bioorg.2022.105791
PMID: 35413582
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2120
DOI:10.1016/j.bioorg.2022.105791