Design, synthesis and biological evaluation of conformationnally-restricted analogues of E7010 as inhibitors of tubulin assembly (ITA) and vascular disrupting agents (VDA) - Université Clermont Auvergne Accéder directement au contenu
Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2022

Design, synthesis and biological evaluation of conformationnally-restricted analogues of E7010 as inhibitors of tubulin assembly (ITA) and vascular disrupting agents (VDA)

Résumé

Vascular-disrupting agents (VDA) specifically target established neovasculature which results in vascular shutdown. This therapeutic strategy could improve the outcome of pathologies involving aberrant angiogenesis. Although several classes of VDA exist, inhibitors of tubulin assembly (ITA) represent the main category. A series of 21 conformationnally-restricted analogues of E7010, a known ITA-VDA, were designed and synthesised as novel inhibitors of tubulin assembly (ITA) and vascular-disrupting agents (VDA). Among them, indole 4j exhibited good potency against HUVEC and HIG-82 cell lines, as well as a good ability to inhibit tubulin assembly. Furthermore, indole 4j reduced HUVEC migration in a dose-dependent manner, indicating a vascular disrupting activity comparable to that of the gold standard, Combretastatin A4 (CA4).

Domaines

Chimie
Fichier non déposé

Dates et versions

hal-03959739 , version 1 (27-01-2023)

Identifiants

Citer

Vassili Prudhomme, Mélissa Cucca, Lionel Nauton, Elsa Andrieu, Mathilde Fereyrolles, et al.. Design, synthesis and biological evaluation of conformationnally-restricted analogues of E7010 as inhibitors of tubulin assembly (ITA) and vascular disrupting agents (VDA). European Journal of Medicinal Chemistry, 2022, 244, pp.114809. ⟨10.1016/j.ejmech.2022.114809⟩. ⟨hal-03959739⟩
43 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More