Molecular structure and activity toward DNA of baicalein, a flavone constituent of the Asian herbal medicine "Sho-saiko-to".
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) A. 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.
Rossi
M
M
Department of Chemistry, Vassar College, Poughkeepsie, New York 12604, Istituto di Strutturistica Chimica, CNR, 00016, Monterotondo Stazione, Rome, Italy. rossi@vassar.edu
Meyer
R
R
Constantinou
P
P
Caruso
F
F
Castelbuono
D
D
O'Brien
M
M
Narasimhan
V
V
D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D004247:DNA / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044950:Flavanones; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D059005:Topoisomerase II Inhibitors
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D059005:Topoisomerase II Inhibitors; C006680:baicalein; C018142:saiko-keishi-to; D004247:DNA