Title :

Methylene versus carbonyl bridge in the structure of new tubulin polymerization inhibitors with tricyclic A-rings

Author(s) :

Moise, Iuliana-Monica [Auteur]
Bicu, Elena [Auteur]
Dubois, Joelle [Auteur]
Farce, Amaury [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Rigo, Benoit [Auteur]
Ghinet, Alina [Auteur]
Lille Inflammation Research International Center (LIRIC) - U995
Lille Inflammation Research International Center (LIRIC) - U995

Journal title :

Bioorganic & medicinal chemistry

Abbreviated title :

Bioorg. Med. Chem.

Volume number :

24

Pages :

6021-6030

Publication date :

2016-11-15

ISSN :

0968-0896

English keyword(s) :

Phenothiazine
Antitumor agent
9(10H)Acridone
Iminodibenzyl
Phenoxazine
Azaphenothiazine
Tubulin inhibitor

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

The phenothiazine group has been identified as a suitable A ring in the structure of tubulin polymerization inhibitors. In our search to identify more potent inhibitors, a study of different isosteric tricyclic groups as ...
Show more >The phenothiazine group has been identified as a suitable A ring in the structure of tubulin polymerization inhibitors. In our search to identify more potent inhibitors, a study of different isosteric tricyclic groups as new potential A rings was first realized and permitted to identify 1-azaphenothiazine and iminodibenzyl as favorable modulations providing compounds with improved activity against tubulin. An investigation of the methylene group as the connector between the A and B rings revealed that the "CH" bridge was tolerated, improving the biological potency when the A unit was of phenothiazine, 1-azaphenothiazine or iminodibenzyl type. Molecules 6-8 and 12 showed increased biological activity in comparison to parent phenstatin 2 on COLO 205 colon cancer cell line. The most antineoplastic agent in the current study was phenothiazine 5 displaying a GI of 25nM against the melanoma MDA-MB-435 cell line.Show less >

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

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

Research team(s) :

Therapeutic innovation targetting inflammation

Submission date :

2019-05-17T13:14:41Z