One-Pot Synthesis of Benzopyran-4-ones with Cancer Preventive and Therapeutic Potential
authors Talhi, O; Brodziak-Jarosz, L; Panning, J; Orlikova, B; Zwergel, C; Tzanova, T; Philippot, S; Pinto, DCGA; Paz, FAA; Gerhauser, C; Dick, TP; Jacob, C; Diederich, M; Bagrel, D; Kirsch, G; Silva, AMS
nationality International
journal EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
author keywords Medicinal chemistry; Drug discovery; Anticancer agents; Oxygen heterocycles; Domino reactions; Michael addition; Antioxidants
keywords ANTIOXIDANT ACTIVITY; CARCINOMA-CELLS; 2-STYRYLCHROMONES; FLAVONOIDS; CHROMONES; AGENTS; CYTOTOXICITY; DERIVATIVES; XANTHOHUMOL; SCAVENGERS
abstract A one-pot synthesis of novel benzopyran-4-ones is described. In a tandem reaction, organobase-catalysed Michael addition of (RCOCH2COR2)-C-1 on chromone-3-carboxylic acid led to decarboxylation and pyran-4-one ring opening of the latter. This was followed by chromone- and/or chromanone ring closure of the resulting Michael adducts when R-1 is an ortho-hydroxyaryl group. Antioxidant testing of 14 derivatives identified strong antiradical properties of chromanones 3o-r (2.1-3.1 mu mol Trolox equiv./mu mol compound in the DPPH assay). Chromanones 3p and 3r and 2-styrylchromone 3k were also most potent in inducing the cytoprotective Keap1-Nrf2 signalling pathway in a reporter gene assay (fivefold induction at concentrations <3 mu M). Of the seven compounds evaluated for antiproliferative activities, 3k and 3r were the most active, inhibiting leukaemia K562 cell proliferation by 50% after 72 h at concentrations of 4.5 and 7.9 mu M, whereas normal peripheral blood mononuclear cells were not affected.
publisher WILEY-V C H VERLAG GMBH
issn 1434-193X
year published 2016
issue 5
beginning page 965
ending page 975
digital object identifier (doi) 10.1002/ejoc.201501278
web of science category Chemistry, Organic
subject category Chemistry
unique article identifier WOS:000370337700016
  ciceco authors
  impact metrics
journal analysis (jcr 2017):
journal impact factor 2.882
5 year journal impact factor 2.675
category normalized journal impact factor percentile 69.298
dimensions (citation analysis):
altmetrics (social interaction):



 


Apoio

1suponsers_list_ciceco.jpg