One‐Pot Synthesis of Benzopyran‐4‐ones with Cancer Preventive and Therapeutic Potential. Issue 5 (15th January 2016)

• Record Type: Journal Article
• Authors: Talhi, Oualid; Brodziak‐Jarosz, Lidia; Panning, Jana; Orlikova, Barbora; Zwergel, Clemens; Tzanova, Tzvetomira; Philippot, Stéphanie; Pinto, Diana C. G. A.; Paz, Filipe A. Almeida; Gerhäuser, Clarissa; Dick, Tobias P.; Jacob, Claus; Diederich, Marc; Bagrel, Denyse; Kirsch, Gilbert; Silva, Artur M. S.
• Is Part Of: European journal of organic chemistry. Issue 5(2016)
• Page Start: 965
• Page End: 975
• Publication Date: 2016-01-15
• Subjects: Medicinal chemistry -- Drug discovery -- Anticancer agents -- Oxygen heterocycles -- Domino reactions -- Michael addition -- Antioxidants; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201501278
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: A one‐pot synthesis of novel benzopyran‐4‐ones is described. In a tandem reaction, organobase‐catalysed Michael addition of R 1 COCH2 COR 2 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 chromanones3o –r (2.1–3.1 µmol Trolox equiv./µmol compound in the DPPH assay). Chromanones3p and3r and 2‐styrylchromone3k were also most potent in inducing the cytoprotective Keap1‐Nrf2 signalling pathway in a reporter gene assay (fivefold induction at concentrations <3 µM ). Of the seven compounds evaluated for antiproliferative activities, 3k and3r were the most active, inhibiting leukaemia K562 cell proliferation by 50 % after 72 h at concentrations of 4.5 and 7.9 µM, whereas normal peripheral blood mononuclear cells were not affected. Abstract : Chromanones3p and3r and 2‐styrylchromones3k potently activate the Nrf2 response in the AREc32 cell line at low micromolar concentrations (C5 <3 µM ). Compounds3k and3r are also the most active in inhibiting cell proliferation by 50 % after 72 h incubation at concentrations of 4.5 and 7.7 µM, whereas normal peripheral blood mononuclear cells were not affected.