Pharmaceutical Composition Useful as Acetylcholinesterase Inhibitors

Abstract

The present invention relates to pharmaceutical composition comprising the naturally occurring compounds selected from (±) Marrnesin, Columbianetin, Dihydroxanthyletin and substituted coumarin derivatives of 7-allyloxy coumarin, 7-benzyloxy coumarin, 7 -methoxycoumarin, 7-acetyloxy coumarin, 4-methyl-7-hydroxy coumarin and 4-methyl-7-acetyloxy coumarin. The said compositions possess a high degree of acetylcholinesterase inhibitory (AChE) property.

1 . A pharmaceutical composition comprising an effective amount of compound of formula 1, analogs and pharmaceutically acceptable salts thereof; 
       
         
           
           
               
               
           
         
         (i) wherein R1 and R2 is linked with each other via following moiety and collectively makes fused system, and R3 is H; 
       
       
         
           
           
               
               
           
         
         (ii) wherein R1 and R3 is linked with each other via following moiety and collectively makes fused system, and R1 is H; 
       
       
         
           
           
               
               
           
         
         (iii) wherein R1 and R2 is linked with each other via following moiety and collectively makes fused system, and R3 is H; 
       
       
         
           
           
               
               
           
         
         (iv) wherein the value of R, R1, R2, and R3 is selected from the group consisting of: 
         a. R=R2=R3=H; R1=OH; 
         b. R=R2=R3=H; R1=Prenyl; 
         c. R=R2=R3=H; R1=Allyl; 
         d. R=R2=R3=H; R1=2,2-dimethyl alkyne; 
         e. R=R2=R3=H; R1=2,2-dimethyl alkene; 
         f. R=R2=R3=H; R1=Benzyl; 
         g. R=R2=R3=H; R1=Acetyl; 
         h. R=R2=R3=H; R1=Methyl; 
         i. R=R1=R3=H; R2=Prenyl; 
         j. R=R3=H; R1=R2=Prenyl; 
         k. R=R1=R2=H; R3=Prenyl; 
         l. R=Methyl; R1=R2=R3=H; 
         m. R=R1=Methyl; R2=R3=H; 
         n. R=R1=Acetyl; R2=R3=H; 
         o. R=Methyl; R1=R3=H; R2=OH; 
         p. R=Methyl; R1=Benzyl, R2=Benzyloxy, R3=H; 
         q. R=Methyl; R1=Methyl, R2=Methyloxy, R3=H; and 
         r. R=Methyl; R1=Acetyl, R2=Acetyloxy, R3=H, 
         optionally along with the pharmaceutically acceptable carrier, or diluents, wherein the effective dose of composition is ranging between 50 to 100 mg/kg body weight. 
       
     
     
         2 . A composition as claimed in  claim 1 , wherein the compound of general formula I further comprising: 
       
         
           
           
               
               
           
         
       
     
     
         3 . A composition as claimed in  claim 1 , wherein the compound of general formula 1 further comprising: 
       
         
           
           
               
               
           
         
       
     
     
         4 . A composition as claimed in  claim 1 , wherein the compound of general formula 1 further comprising: 
       
         
           
           
               
               
           
         
       
     
     
         5 . A composition as claimed in  claim 1 , wherein the compound of general formula 1 further comprising: 
       
         
           
           
               
               
           
         
       
     
     
         6 . A composition as claimed in  claim 1 , wherein the compound of general formula 1 further comprising: 
       
         
           
           
               
               
           
         
         wherein the value of R, R1, R2, and R3 is selected from the group consisting of: 
         a. R=R2=R3=H; R1=OH; 
         b. R=R2=R3=H; R1=Prenyl; 
         c. R=R2=R3=H; R1=Allyl; 
         d. R=R2=R3=H; R1=2,2-dimethyl alkyne; 
         e. R=R2=R3=H; R1=2,2-dimethyl alkene; 
         f. R=R2=R3=H; R1=Benzyl; 
         g. R=R2=R3=H; R1=Acetyl; 
         h. R=R2=R3=H; R1=Methyl; 
         i. R=R1=R3=H; R2=Prenyl; 
         j. R=R3=H; R1=R2=Prenyl; 
         k. R=R1=R2=H; R3=Prenyl; 
         l. R=Methyl; R1=R2=R3=H; 
         m. R=R1=Methyl; R2=R3=H; 
         n. R=R1=Acetyl; R2=R3=H; 
         o. R=Methyl; R1=R3=H; R2=OH; 
         p. R=Methyl; R1=Benzyl, R2=Benzyloxy, R3=H; 
         q. R=Methyl; R1=Methyl, R2=Methyloxy, R3=H; and 
         r. R=Methyl; R1=Acetyl, R2=Acetyloxy, R3=H. 
       
     
     
         7 . A composition as claimed in  claim 1 , wherein the compound used for the preparation of composition is selected from the group consisting of (±) Marmesin, Columbianetin, dihydroxanthyletin, 7-methoxy coumarin, 7-acetyloxy coumarin, 4-methyl-7-hydroxy coumarin, 7-Allyloxycoumarin, and 7-Benzyloxycoumarin. 
     
     
         8 . A composition as claimed in  claim 1 , wherein the compounds used for the preparation of composition may be from natural source or synthesized. 
     
     
         9 . A composition as claimed in  claim 1 , wherein the composition exhibit more percent memory retention than standard drug Donepezil, in scopolamine induced memory deficit mice. 
     
     
         10 . A composition as claimed in  claim 1 , wherein the composition inhibits cholinesterase up to 49%. 
     
     
         11 . A composition as claimed in  claim 1 , wherein the composition is administered by oral route using a carrier selected from gum acacia and Methyl cellulose. 
     
     
         12 .- 15 . (canceled)