Title :

Structure‐Based Design and Synthesis of Piperidinol‐Containing Molecules as New Mycobacterium abscessus Inhibitors

Author(s) :

De Ruyck, Jerome [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Dupont, Christian [Auteur]
Institut de Recherche en Infectiologie de Montpellier [IRIM]
Lamy, Elodie [Auteur]
Infection et inflammation [2I]
Le Moigne, Vincent [Auteur]
Infection et inflammation [2I]
Biot, Christophe [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Guerardel, Yann [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Herrmann, Jean‐Louis [Auteur]
Infection et inflammation [2I]
Université de Versailles Saint-Quentin-en-Yvelines [UVSQ]
Blaise, Mickaël [Auteur]
Institut de Recherche en Infectiologie de Montpellier [IRIM]
Grassin‐Delyle, Stanislas [Auteur]
Hôpital Foch [Suresnes]
Infection et inflammation [2I]
Kremer, Laurent [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Institut de Recherche en Infectiologie de Montpellier [IRIM]
Dubar, Faustine [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Journal title :

ChemistryOpen

Abbreviated title :

ChemistryOpen

Volume number :

9

Pages :

351-365

Publisher :

Wiley

Publication date :

2020-03-20

English keyword(s) :

mycobacterium abscessus
molecular modeling
structure-activity relationship
phenotypic screening
piperidinol derivatives

HAL domain(s) :

Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique

English abstract : [en]

Non‐tuberculous mycobacterium (NTM) infections, such as those caused by Mycobacterium abscessus, are increasing globally. Due to their intrinsic drug resistance, M. abscessus pulmonary infections are often difficult to ...
Show more >Non‐tuberculous mycobacterium (NTM) infections, such as those caused by Mycobacterium abscessus, are increasing globally. Due to their intrinsic drug resistance, M. abscessus pulmonary infections are often difficult to cure using standard chemotherapy. We previously demonstrated that a piperidinol derivative, named PIPD1, is an efficient molecule both against M. abscessus and Mycobacterium tuberculosis, the agent of tuberculosis, by targeting the mycolic acid transporter MmpL3. These results prompted us to design and synthesize a series of piperidinol derivatives and to determine the biological activity against M. abscessus. Structure‐activity relationship (SAR) studies pointed toward specific sites on the scaffold that can tolerate slight modifications. Overall, these results identified FMD‐88 as a new promising active analogue against M. abscessus. Also, we determined the pharmacokinetics properties of PIPD1 and showed that intraperitoneal administration of this compound resulted in promising serum concentration and an elimination half‐life of 3.2 hours.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Chemical Glycobiology
Computational Molecular Systems Biology

Submission date :

2020-11-23T10:46:23Z
2020-11-23T11:43:25Z