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Novel fluorinated benzimidazole-based scaffolds and their anticancer activity in vitro

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posted on 04.07.2016 by Avninder S. Bhambra, Mark Edgar, Mark Elsegood, Lynne Horsburgh, Vladimir Krystof, Paul D. Lucas, Mariam Mojally, Simon J. Teat, Thomas G. Warwick, George Weaver, Fatemeh Zeinali
A small library of twelve, structurally diverse, fluoroaryl benzimidazoles was prepared using a simple synthetic strategy employing SNAr reactions. This allowed rapid assembly of heterocyclic structures containing linked and tethered fluoroaryl benzimidazoles. X-ray crystal structures of seven compounds were obtained including those of two macrocyclic compounds containing 21- and 24-membered rings. Three tethered fluoroaryl benzimidazole derivatives demonstrated micromolar inhibition against K-562 and MCF-7 cell lines. These compounds, in addition to 1-tetrafluoropyrid-4-yl-2-tetrafluoropyrid-4-ylsulfanyl-1H-benzimidazole, also demonstrated micromolar inhibition against G361 and HOS cell lines. Two of the compounds were found to activate caspases leading to apoptosis.

Funding

The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. We thank the EPSRC UK National Mass Spectrometry Facility at Swansea University for mass spectra. We are grateful to Mr J. Alastair Daley and Mrs P. King for technical support. V. Kryštof gratefully acknowledges support from the Czech Science Foundation (15-15264S). We thank Umm Al-Qura University, Saudi Arabia, Loughborough University, UK, and De Montfort University, UK, for financial support.

History

School

  • Science

Department

  • Chemistry

Published in

Journal of Fluorine Chemistry

Citation

BHAMBRA, A.S. ... et al, 2016. Novel fluorinated benzimidazole-based scaffolds and their anticancer activity in vitro. Journal of Fluorine Chemistry, 188, pp. 99-109.

Publisher

© Elsevier

Version

AM (Accepted Manuscript)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Acceptance date

17/06/2016

Publication date

2016

Notes

This paper was accepted for publication in the journal Journal of Fluorine Chemistry and the definitive published version is available at http://dx.doi.org/doi:10.1016/j.jfluchem.2016.06.009

ISSN

1873-3328

Language

en

Exports