Pharmaceutical compositions for inhibiting angiogenesis comprising plant-derived natural compound

Abstract

The present invention provides a pharmaceutical composition for inhibiting angiogenesis containing a plant-derived natural compound which can be effective for preventing or treating disorders or diseases associated with angiogenesis. The compound used as an active ingredient in the pharmaceutical composition of the present invention suppresses VEGF-induced angiogenic responses without cytotoxicity at a low concentration by inhibiting the expression of an anti-angiogenic factor (for example, VEGF), and thus remarkably improves the safety of a drug.

1 - 13 . (canceled) 
     
     
         14 . A method for inhibiting angiogenesis, the method comprising administering to a subject a composition comprising as an active ingredient a compound represented by Chemical Formula 1 below: 
       
         
           
           
               
               
           
         
         wherein, R 1 , R 2 , and R 3  each are independently hydrogen, C 1-12  alkyl, C 1-12  alkoxy, hydroxy, CN, CONH 2 , halo, oxazolyl, C 1-12  alkylthio, or trifluoro(C 1-2 )alkyl. 
       
     
     
         15 . The method of  claim 14 , wherein R 1 , R 2 , and R 3  each are independently hydrogen, halo, or C 1-12  alkyl. 
     
     
         16 . The method of  claim 14 , wherein the compound inhibits the proliferation of human umbilical vascular endothelial cells (HUVECs). 
     
     
         17 . The method of  claim 16 , wherein the proliferation of HUVECs is inhibited through the inhibition of hypoxia-inducible factor-1α (HIF-1α) expression. 
     
     
         18 . The method of  claim 14 , wherein the compound inhibits tumor cell-induced angiogenesis. 
     
     
         19 . The method of  claim 14 , wherein the compound inhibits hypoxia- or vascular endothelial growth factor (VEGF)-induced angiogenesis. 
     
     
         20 . The method of  claim 14 , wherein the compound inhibits nicotine-induced angiogenesis. 
     
     
         21 . The method of  claim 14 , wherein the composition inhibits the expression of angiogenic factors. 
     
     
         22 . The method of  claim 21 , wherein angiogenic factors include VEGF. 
     
     
         23 . The method of  claim 14 , wherein the composition is used for prevention or treatment of cancers, diabetic retinopathy, retinopathy of prematurity, corneal graft rejection, neovascular glaucoma, erythema, proliferative retinopathy, psoriasis, hemophiliac joints, capillary proliferation within atherosclerotic plaques, keloids, wound granulation, vascular adhesions, rheumatoid arthritis, osteoarthritis, autoimmune diseases, Crohn's disease, restenosis, atherosclerosis, intestinal adhesions, cat scratch disease, ulcers, liver cirrhosis, glomerulonephritis, diabetic nephropathy, malignant nephrosclerosis, thrombotic microangiopathy, organ transplant rejection, glomerulopathy, diabetes, inflammation, neurodegenerative diseases, or nicotine addiction-related vessel diseases. 
     
     
         24 . The method of  claim 14 , wherein the compound is represented by Chemical Formula 2 below: 
       
         
           
           
               
               
           
         
       
     
     
         25 . A method for preventing or treating cancers, diabetic retinopathy, retinopathy of prematurity, corneal graft rejection, neovascular glaucoma, erythema, proliferative retinopathy, psoriasis, hemophiliac joints, capillary proliferation within atherosclerotic plaques, keloids, wound granulation, vascular adhesions, rheumatoid arthritis, osteoarthritis, autoimmune diseases, Crohn's disease, restenosis, atherosclerosis, intestinal adhesions, cat scratch disease, ulcers, liver cirrhosis, glomerulonephritis, diabetic nephropathy, malignant nephrosclerosis, thrombotic microangiopathy, organ transplant rejection, glomerulopathy, diabetes, inflammation, neurodegenerative diseases, or nicotine addiction-related vessel diseases, the method comprising administering a subject a composition comprising as an active ingredient a compound represented by Chemical Formula 1 below: 
       
         
           
           
               
               
           
         
         wherein, R 1 , R 2 , and R 3  each are independently hydrogen, C 1-12  alkyl, C 1-12  alkoxy, hydroxy, CN, CONH 2 , halo, oxazolyl, C 1-12  alkylthio, or trifluoro(C 1-2 )alkyl. 
       
     
     
         26 . The method of  claim 25 , wherein R 1 , R 2 , and R 3  each are independently hydrogen, halo, or C 1-12  alkyl. 
     
     
         27 . The method of  claim 25 , wherein the compound is represented by Chemical Formula 2 below: