Literature DB >> 16610804

Design and synthesis of 1-indol-1-yl-propan-2-ones as inhibitors of human cytosolic phospholipase A2alpha.

Joachim Ludwig1, Stefanie Bovens, Carsten Brauch, Alwine Schulze Elfringhoff, Matthias Lehr.   

Abstract

The synthesis and structure-activity relationship study of a series of 1-indol-1-yl-3-phenoxypropan-2-one inhibitors of cytosolic phospholipase A(2)alpha (cPLA(2)alpha) are described. The compounds were evaluated in a vesicle assay with isolated cPLA(2)alpha and in cellular assays with intact human platelets. Systematic variation led to 3-methylhydrogen 1-[3-(4-decyloxyphenoxy)-2-oxopropyl]indole-3,5-dicarboxylate (57), which revealed the highest activity against the isolated enzyme. With an IC(50) value of 4.3 nM in this assay, it is one of the most potent in vitro cPLA(2)alpha inhibitors known today.

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Year:  2006        PMID： 16610804     DOI： 10.1021/jm051243a

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  15 in total

Review 1.  Phospholipase A2 enzymes: physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention.

Authors:  Edward A Dennis; Jian Cao; Yuan-Hao Hsu; Victoria Magrioti; George Kokotos
Journal:  Chem Rev       Date:  2011-09-12       Impact factor: 60.622

2.  Role of cytosolic phospholipase A(2) in retinal neovascularization.

Authors:  Joshua M Barnett; Gary W McCollum; John S Penn
Journal:  Invest Ophthalmol Vis Sci       Date:  2009-08-06       Impact factor: 4.799

3.  Binding conformation of 2-oxoamide inhibitors to group IVA cytosolic phospholipase A2 determined by molecular docking combined with molecular dynamics.

Authors:  Varnavas D Mouchlis; Vasiliki Michopoulou; Violetta Constantinou-Kokotou; Thomas Mavromoustakos; Edward A Dennis; George Kokotos
Journal:  J Chem Inf Model       Date:  2012-01-10       Impact factor: 4.956

Review 4.  Localization and function of cytosolic phospholipase A2alpha at the Golgi.

Authors:  Christina C Leslie; Todd A Gangelhoff; Michael H Gelb
Journal:  Biochimie       Date:  2010-03-10       Impact factor: 4.079

5.  Interfacial kinetic and binding properties of mammalian group IVB phospholipase A2 (cPLA2beta) and comparison with the other cPLA2 isoforms.

Authors:  Farideh Ghomashchi; Gajendra S Naika; James G Bollinger; Ahmed Aloulou; Matthias Lehr; Christina C Leslie; Michael H Gelb
Journal:  J Biol Chem       Date:  2010-08-11       Impact factor: 5.157

6.  2-Oxoamide inhibitors of cytosolic group IVA phospholipase A2 with reduced lipophilicity.

Authors:  Georgia Antonopoulou; Victoria Magrioti; Maroula G Kokotou; Aikaterini Nikolaou; Efrosini Barbayianni; Varnavas D Mouchlis; Edward A Dennis; George Kokotos
Journal:  Bioorg Med Chem       Date:  2016-07-27       Impact factor: 3.641

7.  Structure-activity relationships of natural and non-natural amino acid-based amide and 2-oxoamide inhibitors of human phospholipase A(2) enzymes.

Authors:  Georgia Antonopoulou; Efrosini Barbayianni; Victoria Magrioti; Naomi Cotton; Daren Stephens; Violetta Constantinou-Kokotou; Edward A Dennis; George Kokotos
Journal:  Bioorg Med Chem       Date:  2008-11-01       Impact factor: 3.641

8.  Synthesis of polyfluoro ketones for selective inhibition of human phospholipase A2 enzymes.

Authors:  Constantinos Baskakis; Victoria Magrioti; Naomi Cotton; Daren Stephens; Violetta Constantinou-Kokotou; Edward A Dennis; George Kokotos
Journal:  J Med Chem       Date:  2008-12-25       Impact factor: 7.446

9.  Location of inhibitors bound to group IVA phospholipase A2 determined by molecular dynamics and deuterium exchange mass spectrometry.

Authors:  John E Burke; Arneh Babakhani; Alemayehu A Gorfe; George Kokotos; Sheng Li; Virgil L Woods; J Andrew McCammon; Edward A Dennis
Journal:  J Am Chem Soc       Date:  2009-06-17       Impact factor: 15.419

10.  Pharmacophore-based discovery of a novel cytosolic phospholipase A(2)α inhibitor.

Authors:  Stefan M Noha; Bianca Jazzar; Susanne Kuehnl; Judith M Rollinger; Hermann Stuppner; Anja M Schaible; Oliver Werz; Gerhard Wolber; Daniela Schuster
Journal:  Bioorg Med Chem Lett       Date:  2011-11-30       Impact factor: 2.823
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