Retinobenzoic acids. 2. Structure-activity relationships of chalcone-4-carboxylic acids and flavone-4'-carboxylic acids.

Abstract

The structure-activity relationships of (E)-chalcone-4-carboxylic acids, which are retinoidal benzoic acids represented by R-Ph-X-Ph-COOH (4, X = -COCH = CH-), are discussed on the basis of differentiation-inducing activity on human promyelocytic leukemia cells HL-60. The activity was increased by the substitution of a bulky alkyl group(s) (R), and among such compounds, (E)-4-[3-(3,5-di-tert-butylphenyl)-3-oxo-1-propenyl]benzoic acid (Ch55) and (E)-4-[3-oxo-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1 -propenyl]benzoic acid (Ch80) are several times more active than retinoic acid. Though the stable conformer of chalcone derivatives is linear (s-cis form), the conformationally restricted analogue 4-(6,7,8,9-tetrahydro-6,6,9,9-tetramethyl-4H-4-oxonaphtho[2,3-b]py ran-2-yl)benzoic acid (Fv80) is more active than Ch80. While the effect of introduction of an oxygen atom varied, 4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl-2 - naphthalenyl)-1-propenyl]benzoic acid (Re80), regarded as a derivative of Ch80 with two additional hydroxyl groups, has very strong activity.

• Authors: H Kagechika, E Kawachi, Y Hashimoto, K Shudo
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 32 Issue 4 Pg. 834-40 (Apr 1989) ISSN: 0022-2623 [Print] United States
• PMID: 2704028 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carboxylic Acids
• Flavonoids
• Propiophenones
• Chalcone

Topics

• Carboxylic Acids (pharmacology)
• Cell Differentiation (drug effects)
• Chalcone (analogs & derivatives, pharmacology)
• Chemical Phenomena
• Chemistry
• Chemistry, Physical
• Flavonoids (pharmacology)
• Humans
• Leukemia, Promyelocytic, Acute (pathology)
• Molecular Conformation
• Molecular Structure
• Propiophenones (analogs & derivatives, pharmacology)
• Structure-Activity Relationship
• Tumor Cells, Cultured