Titre :

Synthesis and biological evaluation of phenstatin metabolites

Auteur(s) :

Ghinet, Alina [Auteur]
Rigo, Benoit [Auteur]
Henichart, Jean-Pierre [Auteur]
Le Broc-Ryckewaert, Delphine [Auteur]
Pommery, Jean [Auteur]
Pommery, Nicole [Auteur]
Thuru, Xavier [Auteur]
Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer

Quesnel, Bruno [Auteur]
Gautret, Philippe [Auteur]

Titre de la revue :

Bioorganic & medicinal chemistry

Nom court de la revue :

Bioorg. Med. Chem.

Numéro :

19

Pagination :

6042-6054

Date de publication :

2011-10-15

ISSN :

0968-0896

Mot(s)-clé(s) en anglais :

Metabolite
Anticancer agent
Tubulin
Eaton''s reagent
Friedel-Crafts acylation
Murine leukemia
Phenstatin

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Previous investigations on the incubation of phenstatin with rat and human microsomal fractions revealed the formation of nine main metabolites. The structures of eight of these metabolites have been now confirmed by ...
Lire la suite >Previous investigations on the incubation of phenstatin with rat and human microsomal fractions revealed the formation of nine main metabolites. The structures of eight of these metabolites have been now confirmed by synthesis and their biological properties have been reported. Eaton's reagent was utilized as a convenient condensing agent, allowing, among others, a simple multigram scale preparation of phenstatin. Synthesized metabolites and related compounds were evaluated for their antiproliferative activity in the NCI-60 cancer cell line panel, and for their effect on microtubule assembly. Metabolite 23 (2'-methoxyphenstatin) exhibited the most potent in vitro cytotoxic activity: inhibition of the growth of K-562, NCI-H322M, NCI-H522, KM12, M14, MDA-MB-435, NCI/ADR-RES, and HS 578T cell lines with GI(50) values <10nM. It also showed more significant tubulin polymerization inhibitory activity than parent phenstatin (3) (IC(50)=3.2 μM vs 15.0 μM) and induced G2/M arrest in murine leukemia DA1-3b cells. The identification of this active metabolite led to the design and synthesis of analogs with potent in vitro cytotoxicity and inhibition of microtubule assembly.Lire moins >

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• Lille Neurosciences & Cognition (LilNCog) - U 1172

Équipe(s) de recherche :

Therapeutic innovation targetting inflammation

Date de dépôt :

2019-05-17T13:08:46Z
2021-06-24T13:19:28Z