Toggle Main Menu Toggle Search

ePrints

Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: Potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells

Lookup NU author(s): Dr Jane Renwick, Professor Gareth Veal, Dr Chris Redfern

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

The synthesis and potent inhibitory activity of novel 4-[(imidazol-1-yl and triazol-1-yl)(phenyl)methyl]aryl-and heteroaryl amines versus a MCF-7 CYP26A1 cell assay is described. Biaryl imidazole ([4-(imidazol-1-yl-phenyl-methyl)-phenyl]-naphthalen-2-yl-amine (8), IC50 = 0.5 μM; [4-(imidazol-1-yl-phenyl-methyl)-phenyl]-indan-5-yl-amine (9), IC50 = 1.0 μM) and heteroaryl imidazole derivatives ((1H-benzoimidazol-2-yl)-{4-[(5H-imidazol-1-yl)-phenyl-methyl]-phenyl}-amine (15), IC50 = 2.5 μM; benzooxazol-2-yl-{4-[(5H-imidazol-1-yl)-phenyl-methyl]-phenyl}-amine (16), IC50 = 0.9 μM; benzothiazol-2-yl-{4-[(5H-imidazol-1-yl)-phenyl-methyl]-phenyl}-amine (17), IC50 = 1.5 μM) were the most potent CYP26 inhibitors. Using a CYP26A1 homology model differences in activity were investigated. Incubation of SH-SY5Y human neuroblastoma cells with the imidazole aryl derivative 8, and the imidazole heteroaryl derivatives 16 and 17 potentiated the atRA-induced expression of CYP26B1. These data suggest that further structure-function studies leading to clinical development are warranted. © 2007 Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): Gomaa MS, Armstrong JL, Bobillon B, Veal GJ, Brancale A, Redfern CPF, Simons C

Publication type: Article

Publication status: Published

Journal: Bioorganic and Medicinal Chemistry

Year: 2008

Volume: 16

Issue: 17

Pages: 8301-8313

ISSN (print): 0968-0896

ISSN (electronic): 1464-3391

Publisher: Pergamon

URL: http://dx.doi.org/10.1016/j.bmc.2007.06.048

DOI: 10.1016/j.bmc.2007.06.048


Altmetrics

Altmetrics provided by Altmetric


Actions

    Link to this publication


Share