Please use this identifier to cite or link to this item:
Title: Synthesis and Antitumor Molecular Mechanism of Agents Based on Amino 2-(3',4',5'-Trimethoxybenzoyl)benzo[b]furan: Inhibition of Tubulin and Induction of Apoptosis
Authors: Romagnoli, Romeo
Baraldi, Pier Giovanni
Lopez-Cara, Carlota
Cruz-Lopez, Olga
Carrion, Maria Dora
KimatraiSalvador, Maria
Bermejo, Jaime
Estévez, Sara 
Estévez, Francisco 
Balzarini, Jan
Brancale, Andrea
Ricci, Antonio
Chen, Longchuan
Kim, Jae Gwan
Hamel, Ernest
UNESCO Clasification: 32 Ciencias médicas
2403 Bioquímica
Keywords: Alpha-Halogenoacrylic Derivatives
Vascular Disrupting Agent
Blood-Flow Stasis
Combretastatin Analogs, et al
Issue Date: 2011
Project: Evaluación de Potenciales Compuestos Antileucémicos. 
Journal: ChemMedChem 
Abstract: Induction of apoptosis is a promising strategy that could lead to the discovery of new molecules active in cancer chemotherapy. This property is generally observed when cells are treated with agents that target microtubules, dynamic structures that play a crucial role in cell division. Small molecules such as benzo[b]furans are attractive as inhibitors of tubulin polymerization. A new class of inhibitors of tubulin polymerization based on the 2-(3',4',5'-trimethoxybenzoyl)benzo[b]furan molecular skeleton, with the amino group placed at different positions on the benzene ring, were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell-cycle effects. The methoxy substitution pattern on the benzene portion of the benzo[b]furan moiety played an important role in affecting antiproliferative activity. In the series of 5-amino derivatives, the greatest inhibition of cell growth occurred if the methoxy substituent is placed at the C6 position, whereas C7 substitution decreases potency. The most promising compound in this series is 2-(3', 4', 5'-trimethoxybenzoyl)-3-methyl-5-amino-6-methoxybenzo[b]furan (3h), which inhibits cancer cell growth at nanomolar concentrations (IC(50)=16-24 nm), and interacts strongly with tubulin by binding to the colchicine site. Sub-G(1) apoptotic cells in cultures of HL-60 and U937 cells were observed by flow cytometric analysis after treatment with 3h in a concentration-dependent manner. We also show that compound 3h induces apoptosis by activation of caspase-3, -8, and -9, and this is associated with cytochrome c release from mitochondria. The introduction of an alpha-bromoacryloyl group increased antiproliferative activity with respect to the parent amino derivatives.
ISSN: 1860-7179
DOI: 10.1002/cmdc.201100279
Source: ChemMedChem[ISSN 1860-7179],v. 6, p. 1841-1853
Appears in Collections:Artículos
Show full item record


checked on Sep 24, 2023


checked on Jul 9, 2023

Page view(s)

checked on May 6, 2023

Google ScholarTM




Export metadata

Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.