Gamma-butyrolactone compound and pharmaceutical composition thereof

Abstract

A γ-butyrolactone compound as shown in Formula (I) and pharmaceutical composition thereof: wherein X═N, O, S, Se; and A and B are selected from substituents having the following formula: wherein R 1 , R 2 , R 3 , R 4 , and R 5 are selected from a hydrogen atom, a halogen atom, a hydroxyl group, a mercapto group, an amino group, an alkoxy group, and a nitro group. The γ-butyrolactone compound and pharmaceutical composition thereof butyrolactone have inhibitory effects on hepatoma, ovarian cancer, breast cancer, lung cancer, malignant glioblastoma or colorectal carcinoma, and are cytotoxic with high specificity to inhibit Paclitaxel-resistant tumour cells at later stage of chemotherapy without any damage on normal cells.

1 . A γ-butyrolactone compound as shown in Formula (I):  
       
         
           
           
               
               
           
         
       
       wherein X═N, O, S, Se; and A and B are selected from substituents having the following formula:  
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3 , R 4 , R 5  are selected from a hydrogen atom, a halogen atom, a hydroxyl group, a mercapto group, an amino group, an alkoxy group, and a nitro group.  
       
     
     
         2 . The γ-butyrolactone compound of  claim 1 , wherein the A and B substituents are selected from following substituent structures:  
       
         
           
           
               
               
           
         
       
     
     
         3 . The γ-butyrolactone compound of  claim 1 , wherein a carbon 2(5) position of the γ-butyrolactone compound is a heterocyclic compound having a Z configuration.  
     
     
         4 . The γ-butyrolactone compound of  claim 1 , wherein a carbon 2(5) position of the γ-butyrolactone compound is a heterocyclic compound having an E configuration.  
     
     
         5 . The γ-butyrolactone compound of  claim 1 , wherein the γ-butyrolactone compound is shown in Formula (II) and is named Chaihulactone  
       
         
           
           
               
               
           
         
         wherein R represents an alkoxy group.  
       
     
     
         6 . The γ-butyrolactone compound of  claim 1 , wherein the γ-butyrolactone compound is shown in Formula (III) and is named Isochaihulactone  
       
         
           
           
               
               
           
         
         wherein R represents hydrogen atom, an alkoxy group or aromatic group.  
       
     
     
         7 . A use of any one compound of claims  1 - 6 , wherein the compound is used to manufacture a medicine.  
     
     
         8 . A method for preparing extracts from  Bupleurum scorzonerifolium , which comprising a γ-butyrolactone compound shown in Formula (I) as an active ingredient:  
       
         
           
           
               
               
           
         
         (wherein X═N, O, S, Se; and A and B are selected from substituents having the following formula:  
         
           
             
             
                 
                 
             
           
         
         wherein R 1 , R 2 , R 3 , R 4 , R 5  are selected from a hydrogen atom, a halogen atom, a hydroxyl group, a mercapto group, an amino group, an alkoxy group, and a nitro group),  
         the method comprising steps of:  
         extracting a lignan mixture from  Bupleurum scorzonerifolium  wherein the lignan mixture further comprises at least one antineoplastic component; and  
         isolating a  Bupleurum scorzonerifolium  extract from the lignan mixture.  
       
     
     
         9 . The method of  claim 7 , wherein the step of extracting a lignan mixture from  Bupleurum scorzonerifolium  further comprising steps of: 
 dissolving  Bupleurum scorzonerifolium  powder using a first solution to obtain a first extract and residues;    extracting from the residues using a second solution to obtain a second extract;    extracting the first extract using a third solution to obtain a third extract and an alcohol portion, and dehydrating alcohol in the alcohol portion to obtain an aqueous portion; and    extracting and concentrating the aqueous portion using a fourth solution, wherein the first, second, third, and fourth solution have different polarity from each other.    
     
     
         10 . The method of  claim 7 , wherein the first solution is acetone.  
     
     
         11 . The method of  claim 7 , wherein the second solution is methanol.  
     
     
         12 . The method of  claim 7 , wherein the third solution is 95% methanol solution.  
     
     
         13 . The method of  claim 7 , wherein the fourth solution is chloroform.  
     
     
         14 . The method of  claim 7 , wherein the γ-butyrolactone compound is shown in Formula (II) and is named Chaihulactone:  
       
         
           
           
               
               
           
         
         where R represents a methoxyl group.  
       
     
     
         15 . The method of  claim 7 , wherein the γ-butyrolactone compound is shown in Formula (III) and is named Isochaihulactone:  
       
         
           
           
               
               
           
         
         where R represents a hydrogen atom, a methoxyl group, or an aromatic group.  
       
     
     
         16 . The method of any one of claims  7 - 14 , wherein the A and B substituents are selected from following substituent structures:  
       
         
           
           
               
               
           
         
       
     
     
         17 . The method of any one of claims  7 - 14 , wherein a carbon 2(5) position of the γ-butyrolactone compound is a heterocyclic compound having a Z configuration.  
     
     
         18 . The method of any one of claims  7 - 14 , wherein a carbon 2(5) position of the γ-butyrolactone compound is a heterocyclic compound having an E configuration.  
     
     
         19 . A pharmaceutical composition for treating cell proliferative disorder, which is characterized by comprising a γ-butyrolactone compound shown in Formula (I) as an active ingredient:  
       
         
           
           
               
               
           
         
       
       wherein X═N, O, S, Se; and A and B are selected from substituents having the following formula:  
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3 , R 4 , R 5  are selected from a hydrogen atom, a halogen atom, a hydroxyl group, a mercapto group, an amino group, an alkoxy group, and a nitro group.  
       
     
     
         20 . The pharmaceutical composition of  claim 18 , wherein the A and B substituents are selected from following substituent structures:  
       
         
           
           
               
               
           
         
       
     
     
         21 . The pharmaceutical composition of  claim 18 , wherein a carbon 2(5) position of the γ-butyrolactone compound is a heterocyclic compound having a Z configuration.  
     
     
         22 . The pharmaceutical composition of  claim 18 , wherein a carbon 2(5) position of the γ-butyrolactone compound is a heterocyclic compound having an E configuration.  
     
     
         23 . The pharmaceutical composition of  claim 18 , the γ-butyrolactone compound is shown in Formula (II) and is named Chaihulactone:  
       
         
           
           
               
               
           
         
       
       wherein R represents an alkoxy group.  
     
     
         24 . The pharmaceutical composition of  claim 18 , wherein the γ-butyrolactone compound is shown in Formula (III) and is named Isochaihulactone  
       
         
           
           
               
               
           
         
       
       wherein R represents hydrogen atom, alkoxy group or aromatic group.  
     
     
         25 . The pharmaceutical composition of  claim 18 , wherein the cell proliferative disorder is a malignant cancer.  
     
     
         26 . The pharmaceutical composition of  claim 24 , wherein the malignant cancer is one selected from a group consisting of hepatoma, ovarian cancer, breast cancer, human malignant glioblastoma, and human colorectal cancer.  
     
     
         27 . The pharmaceutical composition of  claim 18 , wherein the cell proliferative disorder develops drug-resistance when treated with Paclitaxel.  
     
     
         28 . A pharmaceutical composition for anti RNA virus, which is characterized by having a γ-butyrolactone compound shown in Formula (I) as an active ingredient:  
       
         
           
           
               
               
           
         
       
       wherein X═N, O, S, Se; and A and B are selected from substituents having the following formula:  
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3 , R 4 , R 5  are selected from a hydrogen atom, a halogen atom, a hydroxyl group, a mercapto group, an amino group, an alkoxy group, and a nitro group.  
       
     
     
         29 . The pharmaceutical composition of  claim 27 , wherein the A and B substituents are selected from following substituent structures:  
       
         
           
           
               
               
           
         
       
     
     
         30 . The pharmaceutical composition of  claim 27 , wherein a carbon 2(5) position of the γ-butyrolactone compound is a heterocyclic compound having a Z configuration.  
     
     
         31 . The pharmaceutical composition of  claim 27 , wherein a carbon 2(5) position of the γ-butyrolactone compound is a heterocyclic compound having an E configuration.  
     
     
         32 . The pharmaceutical composition of  claim 27 , the γ-butyrolactone compound is shown in Formula (II) and is named Chaihulactone:  
       
         
           
           
               
               
           
         
       
       wherein R represents an alkoxy group.  
     
     
         33 . The pharmaceutical composition of  claim 27 , wherein the γ-butyrolactone compound is shown in Formula (III) and is named Isochaihulactone  
       
         
           
           
               
               
           
         
       
       wherein R represents hydrogen atom, alkoxy group or aromatic group.  
     
     
         34 . The pharmaceutical composition of  claim 27 , wherein the RNA virus is HIV.  
     
     
         35 . The pharmaceutical composition of  claim 27 , wherein the RNA virus is a RNA virus except HIV.  
     
     
         36 . A pharmaceutical composition for treating disorders associated with abnormal telomerase activity, which is characterized by having a γ-butyrolactone compound shown in Formula (I) as an active ingredient:  
       
         
           
           
               
               
           
         
       
       wherein X═N, O, S, Se; and A and B are selected from substituents having the following formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 5  are selected from a hydrogen atom, a halogen atom, a hydroxyl group, a mercapto group, an amino group, an alkoxy group, and a nitro group.  
     
     
         37 . The pharmaceutical composition of  claim 35 , wherein the A and B substituents are selected from following substituent structures:  
       
         
           
           
               
               
           
         
       
     
     
         38 . The pharmaceutical composition of  claim 35 , wherein a carbon 2(5) position of the γ-butyrolactone compound is a heterocyclic compound having a Z configuration.  
     
     
         39 . The pharmaceutical composition of  claim 35 , wherein a carbon 2(5) position of the γ-butyrolactone compound is a heterocyclic compound having an E configuration.  
     
     
         40 . The pharmaceutical composition of  claim 35 , the γ-butyrolactone compound is shown in Formula (II) and is named Chaihulactone:  
       
         
           
           
               
               
           
         
         wherein R represents an alkoxy group.  
       
     
     
         41 . The pharmaceutical composition of  claim 35 , wherein the γ-butyrolactone compound is shown in Formula (III) and is named Isochaihulactone  
       
         
           
           
               
               
           
         
       
       wherein R represents hydrogen atom, alkoxy group or aromatic group.  
     
     
         42 . The pharmaceutical composition of  claim 35 , wherein the disorders are associated with a enhanced level of telomerase activity.  
     
     
         43 . Any one pharmaceutical composition of claims  18 - 42 , wherein the γ-butyrolactone compound is contained in an extract obtained by one method of claims  7 - 17 .