Synthesis, modeling, and biological evaluation of anti-tubulin indole-substituted furanones.
Antiproliferative
Antitubulin
Heterocyclic
Indole
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 06 2023
15 06 2023
Historique:
received:
18
04
2023
revised:
12
05
2023
accepted:
19
05
2023
medline:
9
6
2023
pubmed:
27
5
2023
entrez:
26
5
2023
Statut:
ppublish
Résumé
Due to the central role of tubulin in various cellular functions, it is a validated target for anti-cancer therapeutics. However, many of the current tubulin inhibitors are derived from complex natural products and suffer from multidrug resistance, low solubility, toxicity issues, and/or the lack of multi-cancer efficacy. As such, there is a continued need for the discovery and development of new anti-tubulin drugs to enter the pipeline. Herein we report on a group of indole-substituted furanones that were prepared and tested for anti-cancer activity. Molecular docking studies showed positive correlations between favorable binding in the colchicine binding site (CBS) of tubulin and anti-proliferative activity, and the most potent compound was found to inhibit tubulin polymerization. These compounds represent a promising new structural motif in the search for small heterocyclic CBS cancer inhibitors.
Identifiants
pubmed: 37236376
pii: S0960-894X(23)00225-1
doi: 10.1016/j.bmcl.2023.129347
pii:
doi:
Substances chimiques
Tubulin
0
Antineoplastic Agents
0
Tubulin Modulators
0
Colchicine
SML2Y3J35T
Indoles
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
129347Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.