Titre :

Investigation of chalcogen bioisosteric replacement in a series of heterocyclic inhibitors of tryptophan 2,3-dioxygenase

Auteur(s) :

Kozlova, A. [Auteur]
Thabault, L. [Auteur]
Dauguet, N. [Auteur]
Deskeuvre, M. [Auteur]
Stroobant, V. [Auteur]
Pilotte, L. [Auteur]
Liberelle, Maxime [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Van Den Eynde, B. [Auteur]
Frederick, Raphaël [Auteur]
Université de Namur [Namur] [UNamur]

Titre de la revue :

European Journal of Medicinal Chemistry

Numéro :

227

Pagination :

113892

Éditeur :

Elsevier

Date de publication :

2023-05-30

ISSN :

0223-5234

Mot(s)-clé(s) :

Isostery
Chalcogen
Selenium
Atypical elements
Tryptophan 2
3-dioxygenase
Cancer immunotherapy

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Selenium is an underexplored element that can be used for bioisosteric replacement of lower molecular weight chalcogens such as oxygen and sulfur. More studies regarding the impact of selenium substitution in different ...
Lire la suite >Selenium is an underexplored element that can be used for bioisosteric replacement of lower molecular weight chalcogens such as oxygen and sulfur. More studies regarding the impact of selenium substitution in different chemical scaffolds are needed to fully grasp this element's potential. Herein, we decided to evaluate the impact of selenium incorporation in a series of tryptophan 2,3-dioxygenase (TDO2) inhibitors, a target of interest in cancer immunotherapy. First, we synthesized the different chalcogen isosteres through Suzuki-Miyaura type coupling. Next, we evaluated the isosteres' affinity and selectivity for TDO2, as well as their lipophilicity, microsomal stability and cellular toxicity on TDO2-expressing cell lines. Overall, chalcogen isosteric replacements did not disturb the on-target activity but allowed for a modulation of the compounds' lipophilicity, toxicity and stability profiles. The present work contributes to our understanding of oxygen/sulfur/selenium isostery towards increasing structural options in medicinal chemistry for the development of novel and distinctive drug candidates.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Date de dépôt :

2024-01-16T01:44:09Z
2024-09-18T08:06:30Z