Synthesis and Cytotoxic Activity of Novel 9-[Hydroxy(Substitutedphenyl) Methyl]-2,2-Dimethyl-2,3,8,9-Tetrahydro-4H,10H-Pyrano [2,3-f ]Chromene-4,10-Diones

Abstract

Chromanone derivatives demonstrate remarkable cytotoxity against a varieties of cancer cell lines. Novel 9-[hydroxy(substitutedphenyl)methyl]-2,2-dimethyl-2,3,8,9- tetrahydro-4H,10H-pyrano[2,3-f]chromene-4,10-diones as Glyasperin analogues were synthesized in four steps from known 4-chromone 1. The key step was the preparation of chromane dione 5a by regioselective intramolecular cyclization reaction in 85% yield. Condensation of 5a with substituted aromatic aldehydes afforded corresponding alpha hydroxybenzyl analogues 6a-6e. The cytotoxic study of the synthesized compounds against breast cancer human cell line (T47D) showed moderate cytotoxic activities (IC50=16-40 μM) compared to the positive control drug vincristin (IC50=2.5 μM).

Keywords

• chromane
• aldol reaction
• cytotoxicity
• chromanone
• glyasperin analogues