Bioactive depside and anthocyanin compounds, compositions, and methods of use

Abstract

Methods for modulating the level of a chemokine in a cell by administering to a cell an effective amount of a depside or an anthocyanin are provided. More particularly, a method for modulating the level of a chemokine in a cell by administering to a cell an effective amount of a depside having the structure of formula (IV): Formula (IV) wherein R is selected from H or CH 3 or an anthocyanin selected from cyanidin 3-glucoside, delphinidin 3-glucoside, or combinations thereof, or an enantiomer, optical isomer, diastereomer, N-oxide, crystalline form, hydrate, or pharmaceutically acceptable salt thereof is provided. Also provided are compounds according to Formulas I-IV, pharmaceutical compositions, unit dosage forms, and food or feed supplements containing such compounds. Methods for treating a condition in a mammal and for treating or ameliorating a condition, such as for example, chronic obstructive pulmonary disease (COPD) by administering an effective amount of a composition containing such compounds are also provided. Further provided is an extract obtained from the fruit of Myrciaria cauliflora containing at least one compound of the present invention in substantially pure form.

1 .- 39 . (canceled) 
     
     
         40 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R 1 , R 2 , and R 3  are independently selected from H, hydroxy, C 1-8 alkoxy, C 1-8 aralkyl, 3- to 8-membered carbocyclic, 3- to 8-membered heterocyclic, 3- to 8-membered aryl, or 3- to 8-membered heteroaryl, acyl, alkylsulfonyl, and arylsulfonyl, wherein each alkyl, alkoxy, aralkyl, carbocyclic, heterocyclic, aryl, heteroaryl, acyl, alkylsulfonyl, and arylsulfonyl is optionally substituted with at least one substituent; 
         R 4  is selected from H, C 1-8 alkyl, C 1-8 alkoxy, 3- to 8-membered carbocyclic, 3- to 8-membered heterocyclic, 3- to 8-membered aryl, or 3- to 8-membered heteroaryl, carboxylate, ester, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, alditol, NR 7 R 8 , OC(R 7 ) 2 COOH, SC(R 7 ) 2 COOH, NHCHR 7 COOH, COR 8 , CO 2 R 8 , sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, thioalkyl, thioester, and thioether, wherein each alkyl, alkoxy, carbocyclic, heterocyclic, aryl, heteroaryl, carboxylate, ester, amide, carbohydrate, amino acid, acyl, alkoxy-substituted acyl, alditol, NR 7 R 8 , OC(R 7 ) 2 COOH, SC(R 7 ) 2 COOH, NHCHR 7 COOH, COR 8 , CO 2 R 8 , sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, thioalkyl, thioester, and thioether is optionally substituted with at least one substituent; 
         R 7  is selected from H, C 1-8 alkyl, carbocycle, aryl, heteroaryl, heterocycle, alkylaryl, alkylheteroaryl, and alkylheterocycle, wherein each alkyl, carbocycle, aryl, heteroaryl, heterocycle, alkylaryl, alkylheteroaryl, and alkylheterocycle may be optionally substituted with at least one substituent; 
         R 8  is selected from H, C 1-8 alkenyl, C 1-8 alkynyl, aryl, carbocycle, heteroaryl, heterocycle, alkylaryl, alkylheteroaryl, alkylheterocycle, and heteroaromatic, wherein each alkyl, alkenyl, alkynyl, aryl, carbocycle, heteroaryl, heterocycle, alkylaryl, alkylheteroaryl, alkylheterocycle, and heteroaromatic may be optionally substituted with at least one substituent; 
         and n is from 1 to 5, 
         with the proviso that R 1  and R 4  cannot both be H and that when R 1  is OCH 3 , R 4  cannot be CH 3 ; or an enantiomer, optical isomer, diastereomer, N-oxide, crystalline form, hydrate, or pharmaceutically acceptable salt thereof. 
       
     
     
         41 . A pharmaceutical composition comprising a compound according to  claim 40  and a pharmaceutically acceptable carrier. 
     
     
         42 . (canceled) 
     
     
         43 . A compound of formula (II): 
       
         
           
           
               
               
           
         
         wherein 
         R 1 , R 2 , and R 3  are independently selected from H, hydroxy, C 1-3 alkyl, and C 1-3 alkoxy, wherein each alkyl and alkoxy is optionally substituted with at least one substituent; 
         R 4  is selected from H, C 1-3 alkyl, and C 1-3 alkoxy wherein each alkyl and alkoxy, is optionally substituted with at least one substituent; 
         R 7  is selected from H, C 1-8 alkyl, carbocycle, aryl, heteroaryl, heterocycle, alkylaryl, alkylheteroaryl, and alkylheterocycle, wherein each alkyl, carbocycle, aryl, heteroaryl, heterocycle, alkylaryl, alkylheteroaryl, and alkylheterocycle may be optionally substituted with at least one substituent; 
         R 8  is selected from H, C 1-8 alkenyl, C 1-8 alkynyl, aryl, carbocycle, heteroaryl, heterocycle, alkylaryl, alkylheteroaryl, alkylheterocycle, and heteroaromatic, wherein each alkyl, alkenyl, alkynyl, aryl, carbocycle, heteroaryl, heterocycle, alkylaryl, alkylheteroaryl, alkylheterocycle, and heteroaromatic may be optionally substituted with at least one substituent; 
         and n is from 1 to 5, 
         with the proviso that R 1  and R 4  cannot both be H and that when R 1  is OCH 3 , R 4  cannot be CH 3 ; or an enantiomer, optical isomer, diastereomer, N-oxide, crystalline form, hydrate, or pharmaceutically acceptable salt thereof. 
       
     
     
         44 . A pharmaceutical composition comprising a compound according to  claim 43  and a pharmaceutically acceptable carrier. 
     
     
         45 . (canceled) 
     
     
         46 . A compound of formula (III): 
       
         
           
           
               
               
           
         
         wherein n is 1-5. 
       
     
     
         47 . A pharmaceutical composition comprising a compound according to  claim 46  and a pharmaceutically acceptable carrier. 
     
     
         48 . (canceled) 
     
     
         49 . A compound of the formula: