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

0463793 - ÚEB 2017 RIV CH eng J - Journal Article
Bhambra, A.S. - Edgar, M. - Elsegood, M.R.J. - Horsburgh, L. - Kryštof, Vladimír - Lucas, P.D. - Mojally, M. - Teat, S. J. - Warwick, T.G. - Weaver, G.W. - Zeinali, F.
Novel fluorinated benzimidazole-based scaffolds and their anticancer activity in vitro.
Journal of Fluorine Chemistry. Roč. 188, AUG (2016), s. 99-109. ISSN 0022-1139. E-ISSN 1873-3328
R&D Projects: GA ČR(CZ) GA15-15264S
Institutional support: RVO:61389030
Keywords : Anticancer activity * Benzimidazole * C-F activation
Subject RIV: FR - Pharmacology ; Medidal Chemistry
Impact factor: 2.101, year: 2016

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-4ylsulfanyl-1H-benzimidazole, also demonstrated micromolar inhibition against G361 and HOS cell lines. Two of the compounds were found to activate caspases leading to apoptosis.
Permanent Link: http://hdl.handle.net/11104/0262889