Novel fluorinated benzimidazole-based scaffolds and their anticancer activity in vitro
journal contributionposted on 04.07.2016, 13:25 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.
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.