Design, Synthesis, Biological Evaluation, and Crystallographic Study of Novel Purine Nucleoside Phosphorylase Inhibitors.


Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
25 05 2023
Historique:
medline: 26 5 2023
pubmed: 3 5 2023
entrez: 3 5 2023
Statut: ppublish

Résumé

Purine nucleoside phosphorylase (PNP) is a well-known molecular target with potential therapeutic applications in the treatment of T-cell malignancies and/or bacterial/parasitic infections. Here, we report the design, development of synthetic methodology, and biological evaluation of a series of 30 novel PNP inhibitors based on acyclic nucleoside phosphonates bearing a 9-deazahypoxanthine nucleobase. The strongest inhibitors exhibited IC

Identifiants

pubmed: 37134237
doi: 10.1021/acs.jmedchem.2c02097
pmc: PMC10226123
doi:

Substances chimiques

Purine-Nucleoside Phosphorylase EC 2.4.2.1
Enzyme Inhibitors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6652-6681

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Auteurs

Jan Skácel (J)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Stefan Djukic (S)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Ondřej Baszczyňski (O)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.
Faculty of Science, Charles University in Prague, Hlavova 2030/8, Prague 2 12843, Czech Republic.

Filip Kalčic (F)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Tadeáš Bílek (T)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Karel Chalupský (K)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Jaroslav Kozák (J)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Alexandra Dvořáková (A)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Eva Tloušt'ová (E)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Zuzana Král'ová (Z)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.
Faculty of Science, Charles University in Prague, Hlavova 2030/8, Prague 2 12843, Czech Republic.

Markéta Šmídková (M)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Jan Voldřich (J)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.
University of Chemistry and Technology, Technická 5, Prague 16628, Czech Republic.

Michaela Rumlová (M)

University of Chemistry and Technology, Technická 5, Prague 16628, Czech Republic.

Petr Pachl (P)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Jiří Brynda (J)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Tereza Vučková (T)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Milan Fábry (M)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.
Institute of Molecular Genetics, The Czech Academy of Science, Vídeňská 1083, Prague 14220, Czech Republic.

Jan Snášel (J)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Iva Pichová (I)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Pavlína Řezáčová (P)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Helena Mertlíková-Kaiserová (H)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

Zlatko Janeba (Z)

Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo nám. 2, Prague 16610, Czech Republic.

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Classifications MeSH