Chemical inhibitor of p53-snail binding and pharmaceutical composition for treating cancer disease containing same as its active ingredient

Abstract

Provided are compounds for inhibiting Snail-p53 binding and therapeutic agents for cancer including the compounds as an effective component. The Snail-p53 binding inhibitors induce expression of p53 in K-Ras mutant cell lines, thereby enabling effective treatment or prevention of K-Ras mutant cancer, such as, pancreatic cancer, lung cancer, cholangioma, and colon cancer, of which diagnosis or treatment is not easy.

1 . A compound represented by Formula 1 below or salt thereof: 
       
         
           
           
               
               
           
         
         wherein in Formula 1, 
         m is an integer of 0 to 10, n and p each are an integer of 0 or 1, 
         Z is selected from the group consisting of —NH(CH 2 ) q CH 3 , —OH, 4-phenylpiperidin group, 4-phenylpiperazine group, isobutylamino group, and isobutyloxy group, and q is an integer of 0 to 9. 
       
     
     
         2 . The compound or salt thereof of  claim 1 , wherein the compound is selected from the group consisting of 2-nonylamino-5,8-dimethoxy-1,4-naphtoquinone; 2-decylamino-5,8-dimethoxy-1,4-naphtoquinone; 3-(5,8-dimethoxy-1,4-dioxo-naphthalene-2-ylthio)propanoic acid; 11-(5,8-dimethoxy-1,4-dioxo-naphthalene-2-ylthio)undecanoic acid; isobutyl-11-(5,8-dimethoxy-1,4-dioxo-1,4-dihydronaphthalene-2-ylthio)-undecanoate; 11-(5,8-dimethoxy-1,4-dioxo-1,4-dihydronaphthalene-2-ylthio)-N-isobutyl undecanamide; and isobutyl 11-(5,8-dimethoxy-1,4-dioxo-1,4-dihydronaphthalene-2-ylsulfinyl)undecanoate. 
     
     
         3 . A therapeutic agent for cancer, comprising a compound for inhibiting Snail-p53 binding as an effective component. 
     
     
         4 . The therapeutic agent of  claim 3 , wherein the compound is a compound represented by Formula 1 below or salt thereof: 
       
         
           
           
               
               
           
         
         wherein in Formula 1, 
         m is an integer of 0 to 10, n and p each are an integer of 0 or 1, 
         Z is selected from the group consisting of —NH(CH 2 ) q CH 3 , —OH, 4-phenylpiperidin group, 4-phenylpiperazine group, isobutylamino group, and isobutyloxy group, and q is an integer of 0 to 9. 
       
     
     
         5 . The therapeutic agent of  claim 3 , wherein the cancer is a K-Ras mutant cancer. 
     
     
         6 . The therapeutic agent of  claim 5 , wherein the K-Ras mutant cancer is any one selected from the group consisting of pancreatic cancer, lung cancer, cholangioma, and colon cancer. 
     
     
         7 . A method of screening a therapeutic agent for K-Ras mutant cancer, the method comprising:
 culturing Snail and a candidate drug on a plate on which p53 is immobilized; and   screening a candidate drug for inhibiting Snail-p53 binding by using an ELISA leader.   
     
     
         8 . A K-Ras mutant cells specific drug delivery method, comprising delivering a target drug specifically to K-Ras mutant cells by using endocytosis of a DNA binding domain of p53. 
     
     
         9 . The K-Ras mutant cells specific drug delivery method of  claim 8 , wherein the DNA binding domain comprises a sequence of 90-280 of a human p53 amino acid sequence. 
     
     
         10 . The K-Ras mutant cells specific drug delivery method of  claim 8 , the method comprising:
 treating a DNA binding domain of p53 and a target drug into a cell; and   delivering the target drug to neighboring K-Ras mutant cells by endocytosis of the DNA binding domain of p53.   
     
     
         11 . A method of early diagnosing K-Ras mutant cancer, the method comprising detecting expression of a Snail antibody. 
     
     
         12 . The method of  claim 11 , wherein the expression of Snail antibody is detected in a serum of a patient having K-Ras mutant cancer. 
     
     
         13 . The method of  claim 11 , wherein the K-Ras mutant cancer is any one selected from the group consisting of pancreatic cancer, lung cancer, cholangioma, and colon cancer. 
     
     
         14 . The therapeutic agent of  claim 4 , wherein the cancer is a K-Ras mutant cancer. 
     
     
         15 . The K-Ras mutant cells specific drug delivery method of  claim 9 , the method comprising:
 treating a DNA binding domain of p53 and a target drug into a cell; and   delivering the target drug to neighboring K-Ras mutant cells by endocytosis of the DNA binding domain of p53.   
     
     
         16 . The method of  claim 12 , wherein the K-Ras mutant cancer is any one selected from the group consisting of pancreatic cancer, lung cancer, cholangioma, and colon cancer.