Molecular structures of 5,6- and 7,8-benzoflavones, inhibitors of aryl hydrocarbon hydroxylase

The crystal and molecular structures of two isomeric inhibitors of carcinogenesis by certain polycyclic aromatic hydrocarbons are described. The two compounds are 7,8-benzoflavone and 5,6-benzoflavone, which are shown by X-ray crystallographic studies to differ appreciably in their three-dimensional...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1980-08, Vol.40 (8 Pt 1), p.2774
Main Authors: Rossi, M, Cantrell, J S, Farber, A J, Dyott, T, Carrell, H L, Glusker, J P
Format: Article
Language:English
Subjects:
Aryl Hydrocarbon Hydroxylases - antagonists & inhibitors
Aryl Hydrocarbon Hydroxylases - biosynthesis
Benzoflavones - pharmacology
Crystallography
DNA - metabolism
Enzyme Induction - drug effects
Flavonoids - pharmacology
Molecular Conformation
Structure-Activity Relationship
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Summary:The crystal and molecular structures of two isomeric inhibitors of carcinogenesis by certain polycyclic aromatic hydrocarbons are described. The two compounds are 7,8-benzoflavone and 5,6-benzoflavone, which are shown by X-ray crystallographic studies to differ appreciably in their three-dimensional structures. Polycyclic aromatic hydrocarbons are metabolically activated by an enzyme system that is responsibe for the detoxification of many chemicals that enter the body. The two benzoflavones described here differ in their effect towards specific enzymes in the metabolizing system. Potential energy calculations predict that a nonplanar conformation is most probable for these flavone derivatives, as a result of the presence of a biphenyl-like system. Such a conformation is found for 7,8-benzoflavone with a torsion angle of 23 degrees between the phenyl group and the rest of the molecule. The isomeric 5,6-benzoflavone is, in contrast, found to be a predominantly flat molecule. There is an interaction between O(4) and a neighboring -C-H group which may explain the planarity of 5,6-benzoflavone. A comparison is made with structures of some common carcinogenic polycyclic aromatic hydrocarbons, the activities of which these two benzoflavones inhibit.
ISSN:0008-5472