N,N-bis-heteroaryl methylamines: Potent anti-mitotic and highly cytotoxic agents.


Journal

European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510

Informations de publication

Date de publication:
15 Apr 2019
Historique:
received: 07 11 2018
revised: 09 01 2019
accepted: 10 02 2019
pubmed: 1 3 2019
medline: 23 4 2019
entrez: 1 3 2019
Statut: ppublish

Résumé

The synthesis and evaluation of a series of N,N-bis-heterocyclic-methylamines 1 as isoazaerianin analogues are described. It was demonstrated that the replacement of the 3,4,5-trimethoxyphenyl A-ring present in CA-4, isoCA-4 and isoazaerianin by a quinoline or a quinazoline ring is possible and often beneficiary for a high level of cytotoxicity. We have also showed that a carbazole or an indole nucleus are very effective as B-rings in this series, leading to anti-cancer drugs 1 having a sub-nanomolar level of cytotoxicity (1a: IC

Identifiants

pubmed: 30818177
pii: S0223-5234(19)30152-7
doi: 10.1016/j.ejmech.2019.02.038
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Cytotoxins 0
Methylamines 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

176-188

Informations de copyright

Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Auteurs

Ilhem Khelifi (I)

BioCIS, Univ. Paris-Sud, CNRS, Université Paris-Saclay, 92290, Châtenay-Malabry, France.

Timothée Naret (T)

BioCIS, Univ. Paris-Sud, CNRS, Université Paris-Saclay, 92290, Châtenay-Malabry, France.

Abdallah Hamze (A)

BioCIS, Univ. Paris-Sud, CNRS, Université Paris-Saclay, 92290, Châtenay-Malabry, France.

Jérome Bignon (J)

CIBI Platform, Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Avenue de la Terrasse, F-91198, Gif sur Yvette, France.

Hélène Levaique (H)

CIBI Platform, Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Avenue de la Terrasse, F-91198, Gif sur Yvette, France.

Maria Concepcion Garcia Alvarez (MC)

CIBI Platform, Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Avenue de la Terrasse, F-91198, Gif sur Yvette, France.

Joëlle Dubois (J)

CIBI Platform, Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Avenue de la Terrasse, F-91198, Gif sur Yvette, France.

Olivier Provot (O)

BioCIS, Univ. Paris-Sud, CNRS, Université Paris-Saclay, 92290, Châtenay-Malabry, France. Electronic address: olivier.provot@u-psud.fr.

Mouad Alami (M)

BioCIS, Univ. Paris-Sud, CNRS, Université Paris-Saclay, 92290, Châtenay-Malabry, France. Electronic address: mouad.alami@u-psud.fr.

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Classifications MeSH