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

Document Type: Research Article

Authors

1 Iranian Research Institute of Plant Protection (IRIP), Tehran, I.R. IRAN

2 Department of Medicinal Chemistry, Faculty of Pharmacy, and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, I.R. IRAN

3 Department of Medicinal Chemistry, Faculty of Pharmacy, and Drug Design & Development Research Center, Tehran, Tehran University of Medical Sciences, I.R. IRAN

4 Department of Medicinal Chemistry, Faculty of Pharmacy, and Drug Design & Development Research Center, Tehran, Tehran University of Medical Sciences, I.R. IRAN

5 Institute of Biochemistry and Biophysics (IBB), University of Tehran, P.O. Box 13145-1384 Tehran, I.R. IRAN

6 Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran, Tehran University of Medical Sciences, I.R. IRAN

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).

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