Potential bioisosteres of β-uracilalanines derived from 1H-1,2,3-triazole-C-carboxylic acids

Ewa Mironiuk-Puchalska , Włodzimierz Buchowicz , Piotr Grześkowiak , Patrycja Wińska , Monika Wielechowska , Olena Karatsai , Maria Jolanta Rędowicz , Maria Bretner , Mariola Koszytkowska-Stawińska

Abstract

The 1H-1,2,3-triazole-originated derivatives of willardiine were obtained by: (i) construction of the 1H-1,2,3- triazole ring in 1,3-dipolar cycloaddition of the uracil-derived azides and the carboxylate-bearing alkynes or α- acylphosphorus ylide, or (ii) N-alkylation of the uracil derivative with the 1H-1,2,3-triazole-4-carboxylate-derived mesylate. The latter method offered: (i) reproducible results, (ii) a significant reduction of amounts of auxiliary materials, (iii) reduction in wastes and (iv) reduction in a number of manual operations required for obtaining the reaction product. Compound 6a exhibited significant binding affinity to hHS1S2I ligand-binding domain of GluR2 receptor (EC50=2.90 μM) and decreased viability of human astrocytoma MOG-G-CCM cells in higher extent than known AMPA antagonist GYKI 52466.
Author Ewa Mironiuk-Puchalska (FC / DOC)
Ewa Mironiuk-Puchalska,,
- Department Of Organic Chemistry
, Włodzimierz Buchowicz (FC / DOC)
Włodzimierz Buchowicz,,
- Department Of Organic Chemistry
, Piotr Grześkowiak (FC / DOC)
Piotr Grześkowiak,,
- Department Of Organic Chemistry
, Patrycja Wińska (FC / CDSB)
Patrycja Wińska,,
- Chair of Drug and Cosmetics Biotechnology
, Monika Wielechowska (FC / CDSB)
Monika Wielechowska,,
- Chair of Drug and Cosmetics Biotechnology
, Olena Karatsai
Olena Karatsai,,
-
, Maria Jolanta Rędowicz
Maria Jolanta Rędowicz,,
-
, Maria Bretner (FC / CDSB)
Maria Bretner,,
- Chair of Drug and Cosmetics Biotechnology
, Mariola Koszytkowska-Stawińska (FC / DOC)
Mariola Koszytkowska-Stawińska,,
- Department Of Organic Chemistry
Journal seriesBioorganic Chemistry, ISSN 0045-2068, (A 25 pkt)
Issue year2019
Vol83
Pages500-510
Publication size in sheets0.5
Keywords in English1,2,3-Triazoles Nucleobase Uracilalanine Amino acid Willardiine Glutamate receptors Glioblastoma
ASJC Classification1605 Organic Chemistry; 3002 Drug Discovery; 1312 Molecular Biology; 1303 Biochemistry
DOIDOI:10.1016/j.bioorg.2018.10.061
URL https://www.sciencedirect.com/science/article/pii/S0045206818307193
Languageen angielski
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wdpb_publikacje_pliki_plik_publikacja_3609_org.pdf 1.25 MB
Score (nominal)25
ScoreMinisterial score = 25.0, 20-07-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.147; WoS Impact Factor: 2017 = 3.929 (2) - 2017=3.39 (5)
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