Title :

Polycyclic nitrogen heterocycles as potential thymidine phosphorylase inhibitors: synthesis, biological evaluation, and molecular docking study.

Author(s) :

Aknin, Karen [Auteur]
Cibles Thérapeutiques et conception de médicaments [CiTCoM - UMR 8038]
Bontemps, Alexis [Auteur]
Cibles Thérapeutiques et conception de médicaments [CiTCoM - UMR 8038]
Farce, Amaury [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Merlet, E. [Auteur]
Cibles Thérapeutiques et conception de médicaments [CiTCoM - UMR 8038]
Belmont, P. [Auteur]
Cibles Thérapeutiques et conception de médicaments [CiTCoM - UMR 8038]
Helissey, P. [Auteur]
Cibles Thérapeutiques et conception de médicaments [CiTCoM - UMR 8038]
Chavatte, Philippe [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Sari, Marie-Agnès [Auteur]
Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques [LCBPT - UMR 8601]
Giorgi-Renault, S. [Auteur]
Cibles Thérapeutiques et conception de médicaments [CiTCoM - UMR 8038]
Desbène-Finck, S. [Auteur]
Cibles Thérapeutiques et conception de médicaments [CiTCoM - UMR 8038]

Journal title :

Journal of Enzyme Inhibition and Medicinal Chemistry

Abbreviated title :

J Enzyme Inhib Med Chem

Volume number :

37

Pages :

252-268

Publication date :

2021-12-30

ISSN :

1475-6374

English keyword(s) :

Thymidine phosphorylase inhibitor
multicomponent reactions
molecular docking
pyrido[2
3-d]pyrimidinedione
pyrimido[4
5-b]quinoline-2
4-dione

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

New polycyclic heterocycles were synthesised and evaluated as potential inhibitors of thymidine phos-phorylase (TP). Inspired by the pharmacophoric pyrimidinedione core of the natural substrate, four serieshave been designed ...
Show more >New polycyclic heterocycles were synthesised and evaluated as potential inhibitors of thymidine phos-phorylase (TP). Inspired by the pharmacophoric pyrimidinedione core of the natural substrate, four serieshave been designed in order to interact with large empty pockets of the active site: pyrimidoquinoline-2,4-diones (series A), pyrimidinedione linked to a pyrroloquinoline-1,3-diones (series B and C), the polycyc-lic heterocycle has been replaced by a pyrimidopyridopyrrolidinetetraone (series D). In each series, the tri-cyclic nitrogen heterocyclic moiety has been synthesised by a one-pot multicomponent reaction.Compared to7-DXused as control,2d,2l,2p(series A),28a(series D), and the open intermediate30showed modest to good activities. A kinetic study confirmed that the most active compounds2d,2parecompetitive inhibitors. Molecular docking analysis confirmed the interaction of these new compounds atthe active binding site of TP and highlighted a plausible specific interaction in a pocket that had not yetbeen explored.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2024-01-12T05:24:38Z
2024-02-28T10:34:31Z