Use of psoralen derivatives and combination therapy for treatment of cell proliferation disorders

Abstract

Methods for the treatment of a cell proliferation disease or disorder in a subject, involving applying a psoralen derivative lacking a DNA cross-linking motif to cancer cells, applying a psoralen or a derivative thereof and lapatinib, or applying a psoralen or derivative thereof and neratinib, to a subject and further applying initiation radiation energy form an energy source.

1 . A pharmaceutical composition for treatment of a cell proliferation disorder or disease, comprising:
 a psoralen derivative lacking a DNA cross-linking motif; and   a pharmaceutically acceptable carrier,   wherein the psoralen derivative lacking a DNA cross-linking motif is represented by the formula (1):   
       
         
           
           
               
               
           
         
         wherein R 1  is hydrogen, lower alkyl, or lower alkoxy; 
         R 2  and R 3  are each, independently, hydrogen, C 1 -C 6  alkyl, or C 1 -C 6  alkoxy, or R 2  and R 3  may join to form a substituted or unsubstituted, condensed 5 to 7 membered aliphatic or aromatic ring, optionally containing at least one heteroatom selected from N, S, and O; 
         R 4  and R 5  are each, independently, hydrogen, C 1 -C 6  alkyl, or C 1 -C 6  alkoxy, or R 4  and R 5  may join to form a substituted or unsubstituted, condensed 5 to 7 membered aliphatic or aromatic ring, optionally containing at least one heteroatom selected from N, S, and O; 
         with the proviso that at least one of R 2  and R 3  or R 4  and R 5  are joined to form a substituted or unsubstituted, condensed 5 to 7 membered aliphatic or aromatic ring, optionally containing at least one heteroatom selected from N, S, and O. 
       
     
     
         2 . The pharmaceutical composition of  claim 1 , further comprising at least one substituted psoralen compound selected from the group consisting of 8-Methoxypsoralen (8-MOP) and 4′-aminomethyl-4,5′,8-trimethylpsoralen (AMT). 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the psoralen derivative lacking a DNA cross-linking motif is SMSF032310. 
     
     
         4 . The pharmaceutical composition of  claim 1 , further comprising at least one energy modulation agent that converts an initiation energy to an energy that activates the psoralen lacking the DNA cross-linking motif. 
     
     
         5 . The pharmaceutical composition of  claim 2 , further comprising at least one energy modulation agent that converts an initiation energy to an energy that activates one or both of the psoralen lacking the DNA cross-linking motif or the substituted psoralen compound. 
     
     
         6 . The pharmaceutical composition of  claim 3 , further comprising at least one energy modulation agent that converts an initiation energy to an energy that activates SMSF032310. 
     
     
         7 . The pharmaceutical composition of  claim 4 , wherein the at least one energy modulation agent is one or more members selected from the group consisting of biocompatible fluorescing metal nanoparticles, fluorescing dye molecules, gold nanoparticles, water soluble quantum dots encapsulated by polyamidoamine dendrimers, a luciferase, biocompatible phosphorescent molecules, combined electromagnetic energy harvester molecules, and lanthanide chelates capable of intense luminescence. 
     
     
         8 . The pharmaceutical composition of  claim 5 , wherein the at least one energy modulation agent is one or more members selected from the group consisting of biocompatible fluorescing metal nanoparticles, fluorescing dye molecules, gold nanoparticles, water soluble quantum dots encapsulated by polyamidoamine dendrimers, a luciferase, biocompatible phosphorescent molecules, combined electromagnetic energy harvester molecules, and lanthanide chelates capable of intense luminescence. 
     
     
         9 . The pharmaceutical composition of  claim 6 , wherein the at least one energy modulation agent is one or more members selected from the group consisting of biocompatible fluorescing metal nanoparticles, fluorescing dye molecules, gold nanoparticles, water soluble quantum dots encapsulated by polyamidoamine dendrimers, a luciferase, biocompatible phosphorescent molecules, combined electromagnetic energy harvester molecules, and lanthanide chelates capable of intense luminescence. 
     
     
         10 . The pharmaceutical composition of  claim 7 , wherein the at least one energy modulation agent is one or more members selected from the group consisting of biocompatible phosphorescent molecules. 
     
     
         11 . The pharmaceutical composition of  claim 8 , wherein the at least one energy modulation agent is one or more members selected from the group consisting of biocompatible phosphorescent molecules. 
     
     
         12 . The pharmaceutical composition of  claim 9 , wherein the at least one energy modulation agent is one or more members selected from the group consisting of biocompatible phosphorescent molecules.