Literature DB >> 21763147

NSAID-derived γ-secretase modulation requires an acidic moiety on the carbazole scaffold.

Andrea Zall1, Daniel Kieser, Nicole Höttecke, Eva C Naumann, Binia Thomaszewski, Katrin Schneider, Dirk T Steinbacher, Robert Schubenel, Stefan Masur, Karlheinz Baumann, Boris Schmidt.   

Abstract

Modulation of γ-secretase activity holds potential for the treatment of Alzheimer's disease. Most NSAID-derived γ-secretase modulators feature a carboxylic acid, which may impair blood-brain barrier permeation. The structure activity relationship of 33 carbazoles featuring diverse carboxylic acid isosteres or metabolic precursors thereof was established in a cellular amyloid secretion assay. The modulatory activity was observed for acidic moieties and metabolically labile esters only, which supports our hypothesis of an acid-lysine interaction to be relevant for this type of γ-secretase modulators.
Copyright © 2011 Elsevier Ltd. All rights reserved.

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Year:  2011        PMID： 21763147     DOI： 10.1016/j.bmc.2011.06.062

Source DB:  PubMed          Journal:  Bioorg Med Chem        ISSN： 0968-0896            Impact factor:   3.641


  6 in total

1.  Coumarin-carbazole based functionalized pyrazolines: synthesis, characterization, anticancer investigation and molecular docking.

Authors:  Mrugesh Patel; Nilesh Pandey; Jignesh Timaniya; Paranjay Parikh; Alex Chauhan; Neeraj Jain; Kaushal Patel
Journal:  RSC Adv       Date:  2021-08-13       Impact factor: 4.036

2.  In Silico and Experimental Investigation of the Biological Potential of Some Recently Developed Carprofen Derivatives.

Authors:  Florea Dumitrascu; Ana-Maria Udrea; Mino R Caira; Diana Camelia Nuta; Carmen Limban; Mariana Carmen Chifiriuc; Marcela Popa; Coralia Bleotu; Anamaria Hanganu; Denisa Dumitrescu; Speranta Avram
Journal:  Molecules       Date:  2022-04-23       Impact factor: 4.927

Review 3.  Development and mechanism of γ-secretase modulators for Alzheimer's disease.

Authors:  Christina J Crump; Douglas S Johnson; Yue-Ming Li
Journal:  Biochemistry       Date:  2013-05-02       Impact factor: 3.162

4.  Steroids as γ-secretase modulators.

Authors:  Joo In Jung; Thomas B Ladd; Thomas Kukar; Ashleigh R Price; Brenda D Moore; Edward H Koo; Todd E Golde; Kevin M Felsenstein
Journal:  FASEB J       Date:  2013-05-28       Impact factor: 5.191

Review 5.  Carboxylic acid (bio)isosteres in drug design.

Authors:  Carlo Ballatore; Donna M Huryn; Amos B Smith
Journal:  ChemMedChem       Date:  2013-01-29       Impact factor: 3.466

6.  Complex relationships between substrate sequence and sensitivity to alterations in γ-secretase processivity induced by γ-secretase modulators.

Authors:  Joo In Jung; Yong Ran; Pedro E Cruz; Awilda M Rosario; Thomas B Ladd; Thomas L Kukar; Edward H Koo; Kevin M Felsenstein; Todd E Golde
Journal:  Biochemistry       Date:  2014-03-20       Impact factor: 3.162
  6 in total

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