Identification of free-B-ring flavonoids as potent COX-2 inhibitors

Abstract

The present invention provides a novel method for inhibiting the cyclooxygenase COX-2. The method is comprised of administering a composition containing a Free-enzyme B-Ring flavonoid or a composition containing a mixture of Free-B-Ring flavonoids to a host in need thereof. The present also includes novel methods for the prevention and treatment of COX-2 mediated diseases and conditions. The method for preventing and treating COX-2 mediated diseases and conditions is comprised of administering to a host in need thereof an effective amount of a composition containing a Free-B-Ring flavonoid or a composition containing a mixture of Free-B-Ring flavonoids and a pharmaceutically acceptable carrier.

What is claimed is  
     
         1 . A method for inhibiting the cyclooxygenase enzyme COX-2 comprising administering a composition comprising a Free-B-Ring flavonoid or a composition containing a mixture of Free-B-Ring flavonoids.  
     
     
         2 . The method of  claim 1  wherein said Free-B-Ring flavonoid is selected from the group of compounds having the following structure:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1 , R 2 , R 3 , R 4 , and R 5  are independently selected from the group consisting of —H, —OH, —SH, —OR, —SR, —NH 2 , —NHR, —NR 2 , —NR 3   + X − , a carbon, oxygen, nitrogen or sulfur, glycoside of a single or a combination of multiple sugars including, aldopentoses, methyl-aldopentose, aldohexoses, ketohexose and their chemical derivatives thereof;  
 wherein 
 R is an alkyl group having between 1-10 carbon atoms; and  
 X is selected from the group of pharmaceutically acceptable counter anions including, hydroxyl, chloride, iodide, sulfate, phosphate, acetate, fluoride and carbonate:  
 
 
     
     
         3 . The method of  claim 1  wherein said Free-B-Ring flavonoid is obtained by organic synthesis.  
     
     
         4 . The method of  claim 1  wherein said Free-B-Ring flavonoid is isolated from a plant part.  
     
     
         5 . The method of  claim 4  wherein said plant is selected from a family consisting of Annonaceae, Asteraceae, Bignoniaceae, Combretaceae, Compositae, Euphorbiaceae, Labiatae, Lauranceae, Leguminosae, Moraceae, Pinaceae, Pteridaceae, Sinopteridaceae, Ulmaceae and Zingiberacea.  
     
     
         6 . The method of  claim 4  wherein said plant is selected from a genus consisting of Desmos, Achyrocline, Oroxylum, Buchenavia, Anaphalis, Cotula, Gnaphalium, Helichrysum, Centaurea, Eupatorium, Baccharis, Sapium, Scutellaria, Molsa, Colebrookea, Stachys, Origanum, Ziziphora, Lindera, Actinodaphne, Acacia, Derris, Glycyrrhiza, Millettia, Pongamia, Tephrosia, Artocarpus, Ficus, Pityrogramma, Notholaena, Pinus, Ulmus and Alpinia.  
     
     
         7 . The method of  claim 4  wherein the Free-B-Ring flavonoid is isolated from a plant part selected from the group consisting of stems, stem barks, twigs, tubers, roots, root barks, young shoots, seeds, rhizomes, flowers and other reproductive organs, leaves and other aerial parts.  
     
     
         8 . A method for preventing and treating COX-2 mediated diseases and conditions comprising administering to a host in need thereof an effective amount of a composition comprising a Free-B-Ring flavonoid or a composition containing a mixture of Free-B-Ring flavonoids and a pharmaceutically acceptable carrier.  
     
     
         9 . The method of  claim 8  wherein said Free-B-Ring flavonoid is selected from the group of compounds having the following structure:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1 , R 2 , R 3 , R 4 , and R 5  are independently selected from the group consisting of —H, —OH, —SH, —OR, —SR, —NH 2 , —NHR, —NR 2 , —NR 3   + X − , a carbon, oxygen, nitrogen or sulfur, glycoside of a single or a combination of multiple sugars including, aldopentoses, methyl-aldopentose, aldohexoses, ketohexose and their chemical derivatives thereof,  
 wherein 
 R is an alkyl group having between 1-10 carbon atoms; and  
 X is selected from the group of pharmaceutically acceptable counter anions including, hydroxyl, chloride, iodide, sulfate, phosphate, acetate, fluoride and carbonate.  
 
 
     
     
         10 . The method of  claim 8  wherein said Free-B-Ring flavonoid is obtained by organic synthesis.  
     
     
         11 . The method of  claim 8  wherein said Free-B-Ring flavonoid is isolated from a plant part.  
     
     
         12 . The method of  claim 11  wherein said plant is selected from a family consisting of Annonaceae, Asteraceae, Bignoniaceae, Combretaceae, Compositae, Euphorbiaceae, Labiatae, Lauranceae, Leguminosae, Moraceae, Pinaceae, Pteridaceae, Sinopteridaceae, Ulmaceae and Zingiberacea.  
     
     
         13 . The method of  claim 11  wherein said plant is selected from a genus consisting Desmos, Achyrocline, Oroxylum, Buchenavia, Anaphalis, Cotula, Gnaphalium, Helichrysum, Centaurea, Eupatorium, Baccharis, Sapium, Scutellaria, Molsa, Colebrookea, Stachys, Origanum, Ziziphora, Lindera, Actinodaphne, Acacia, Derris, Glycyrrhiza, Millettia, Pongamia, Tephrosia, Artocarpus, Ficus, Pityrogramma, Notholaena, Pinus, Ulmus and Alpinia.  
     
     
         14 . The method of  claim 11  wherein the Free-B-Ring flavonoid is isolated from the plant part selected from the group consisting of stems, stem barks, twigs, tubers, roots, root barks, young shoots, seeds, rhizomes, flowers and other reproductive organs, leaves and other aerial parts.  
     
     
         15 . The method of  claim 8  wherein the COX-2 mediated disease or condition is selected from the group consisting of inflammation associated with osteoarthritis, rheumatoid arthritis, menstrual cramps, Systemic Lupus Erythromatosis, psoriasis, chronic tension headache, migraine headaches, inflammatory bowel disease; topical wound and minor inflammation conditions selected from the group consisting of minor abrasions, sunburn and contact dermatitis; and solid cancers.  
     
     
         16 . The method of  claim 8  wherein the Free-B-Ring flavonoid composition is comprised of 0.01% to 100% of the Free-B-Ring flavanoid.  
     
     
         17 . The method of  claim 8  wherein the composition is administered in a dosage selected from 0.01 to 200 mg/kg of body weight.  
     
     
         18 . The method of  claim 8  wherein the routes of the administration are selected from the group consisting of oral, topical, suppository, intravenous, and intradermic, intragaster, intramusclar, intraperitoneal and intravenous administration in an appropriate pharmaceutical formula.