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Molecular Structure and Activity Toward DNA of Baicalein, a Flavone Constituent of the Asian Herbal Medicine “Sho-saiko-to”

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journal contribution
posted on 18.11.2000, 00:00 by Miriam Rossi, Ryan Meyer, Pamela Constantinou, Francesco Caruso, Deborah Castelbuono, Megan O'Brien, Vasantha Narasimhan
Baicalein (5,6,7-trihydroxyflavone, 1) is of interest because of its broad spectrum of biological activity. It is a constituent of the east Asian herbal remedy, “Sho-saiko-to”. The 3D structure of 1 was determined using X-ray diffraction. The compound exists in an almost planar conformation with a C-2C-1‘ bond distance of 1.476(5) Å. Hydrogen-bonding interactions predominate in the crystal structure. The position of the three hydroxyl groups maximizes intramolecular hydrogen bonding, and each of the hydroxyl hydrogen atoms is a donor in a three-center hydrogen bond. The carbonyl oxygen, O-4, is an acceptor in an intramolecular hydrogen bond (with OH-5). Two molecules of 1 exist as hydrogen-bonded dimers related by inversion center (−x + 1, −y, −z + 1). O-4 is also an acceptor in an intermolecular hydrogen bond with OH-6. The planarity of the flavone framework is dependent on structural and/or electronic forces that stabilize the negative charge on the exocyclic oxygen atom, O-4. Compound 1, therefore, is planar in any situation where forces can stabilize the negative charge on O-4. Consistent with this, UV absorbance studies performed on 1−DNA complexes with varying concentrations of 1 strongly suggest intercalation of 1 within the double helix, followed by possible interstrand cross-links.