Design, synthesis and biological evaluation of novel vicinal diaryl-substituted 1H-Pyrazole analogues of combretastatin A-4 as highly potent tubulin polymerization inhibitors.
1H-pyrazole
Antiproliferative activity
Microtubules
Structure-activity relationship
Tubulin
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:
01 Nov 2019
01 Nov 2019
Historique:
received:
26
06
2019
revised:
30
07
2019
accepted:
30
07
2019
pubmed:
11
8
2019
medline:
26
11
2019
entrez:
11
8
2019
Statut:
ppublish
Résumé
A series of 3-(3',4',5'-trimethoxyphenyl)-4-substituted 1H-pyrazole and their related 3-aryl-4-(3',4',5'-trimethoxyphenyl)-1-H-pyrazole regioisomeric derivatives, prepared as cis-rigidified combretastatin A-4 (CA-4) analogues, were synthesized and evaluated for their in vitro antiproliferative against six different cancer cell lines and, for selected highly active compounds, inhibitory effects on tubulin polymerization, cell cycle effects and in vivo potency. We retained the 3',4',5'-trimethoxyphenyl moiety as ring A throughout the present investigation, and a structure-activity relationship (SAR) information was obtained by adding electron-withdrawing (OCF
Identifiants
pubmed: 31400707
pii: S0223-5234(19)30707-X
doi: 10.1016/j.ejmech.2019.111577
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Bibenzyls
0
Pyrazoles
0
Tubulin
0
Tubulin Modulators
0
combretastatin
7O62J06F18
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111577Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.