Design, synthesis, and biological evaluation of a new class of benzo[b]furan derivatives as antiproliferative agents, with in silico predicted antitubulin activity

6533b82afe1ef96bd128c2bf

RESEARCH PRODUCT

Design, synthesis, and biological evaluation of a new class of benzo[b]furan derivatives as antiproliferative agents, with in silico predicted antitubulin activity

Antonio Palumbo-piccionello Silvestre Buscemi Francesco Mingoia Roberta Bartolotta Carla Gentile Riccardo Delisi Antonino Lauria Annamaria Martorana

subject

0301 basic medicine Cell cycle checkpoint induced fit docking studie antitubulin agents 01 natural sciences Biochemistry HeLa and MCF-7 cell lines HeLa chemistry.chemical_compound Tubulin Furan Drug Discovery Imidazole Moiety biology HeLa and MCF-7 cell line G2/M phase Tubulin Modulators Molecular Docking Simulation Antiproliferative Agents MCF-7 Cells Molecular Medicine VLAK protocol antitubulin agent Stereochemistry In silico Substituent 3-benzoylamino-5-(1H-imidazol-4-yl)methylaminobenzo[b]furans Antineoplastic Agents induced fit docking studies antitumor agents 03 medical and health sciences Humans colchicine binding site Benzofurans Cell Proliferation Pharmacology Binding Sites 010405 organic chemistry Organic Chemistry Cell Cycle Checkpoints 3-benzoylamino-5-(1H-imidazol-4-yl)methylaminobenzo[b]furan biology.organism_classification 0104 chemical sciences Protein Structure Tertiary 030104 developmental biology chemistry antitumor agent Drug Design Colchicine HeLa Cells

description

A new series of 3-benzoylamino-5-(1H-imidazol-4-yl)methylaminobenzo[b]furans were synthesized and screened as antitumor agents. As a general trend, tested compounds showed concentration-dependent antiproliferative activity against HeLa and MCF-7 cancer cell lines, exhibiting GI50 values in the low micromolar range. In most cases, insertion of a methyl substituent on the imidazole moiety improved the antiproliferative activity. Therefore, methyl-imidazolyl-benzo[b]furans compounds were tested in cell cycle perturbation experiments, producing cell cycle arrest with proapoptotic effects. Their core similarity to known colchicine binding site binders led us to further study the structure features as antitubulin agents by in silico protocols. This article is protected by copyright. All rights reserved.

year	journal	country	edition	language
2018-01-01

10.1111/cbdd.13052 https://dx.doi.org/10.1111/cbdd.13052