Literature DB >> 25240617

Computational & experimental evaluation of the structure/activity relationship of β-carbolines as DYRK1A inhibitors.

Binia Drung1, Christoph Scholz1, Valéria A Barbosa2, Azadeh Nazari1, Maria H Sarragiotto2, Boris Schmidt3.   

Abstract

DYRK1A has been associated with Down's syndrome and neurodegenerative diseases, therefore it is an important target for novel pharmacological interventions. We combined a ligand-based pharmacophore design with a structure-based protein/ligand docking using the software MOE in order to evaluate the underlying structure/activity relationship. Based on this knowledge we synthesized several novel β-carboline derivatives to validate the theoretical model. Furthermore we identified a modified lead structure as a potent DYRK1A inhibitor (IC50=130 nM) with significant selectivity against MAO-A, DYRK2, DYRK3, DYRK4 & CLK2.
Copyright © 2014 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  DYRK1A; Docking; Inhibitor; MAO-A; Pharmacophore; SAR; β-Carboline

Mesh：

Substances：

Year:  2014        PMID： 25240617     DOI： 10.1016/j.bmcl.2014.08.054

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  7 in total

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2.  Isoform selectivity of harmine-conjugated 1,2,3-triazoles against human monoamine oxidase.

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4.  Identification of harmine and β-carboline analogs from a high-throughput screen of an approved drug collection; profiling as differential inhibitors of DYRK1A and monoamine oxidase A and for in vitro and in vivo anti-cancer studies.

Authors:  Michael Tarpley; Helen O Oladapo; Dillon Strepay; Thomas B Caligan; Lhoucine Chdid; Hassan Shehata; Jose R Roques; Rhashad Thomas; Christopher P Laudeman; Rob U Onyenwoke; David B Darr; Kevin P Williams
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Review 6.  Dyrk1a from Gene Function in Development and Physiology to Dosage Correction across Life Span in Down Syndrome.

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Journal:  Genes (Basel)       Date:  2021-11-20       Impact factor: 4.096

7.  Chemical constituents from Limonium tubiflorum and their in silico evaluation as potential antiviral agents against SARS-CoV-2.

Authors:  Ahmed R Hassan; Ibrahim M Sanad; Ahmed E Allam; Mohamed E Abouelela; Ahmed M Sayed; Shalabia S Emam; Salah M El-Kousy; Kuniyoshi Shimizu
Journal:  RSC Adv       Date:  2021-09-30       Impact factor: 4.036
  7 in total

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