Naphthalimide compositions and uses thereof

Abstract

A method of treatment of a host with a cellular proliferative disease, comprising contacting the host with a naphthalimide and an antiproliferative agent, each in an amount sufficient to modulate said cellular proliferative disease, is described. In some embodiments, the naphthalimide comprises amonafide (5-amino-2-[2-(dimethylamine)ethyl]-1H-benz[de-]isoquinoline-1,3-(2H)-dione). Antiproliferative agents of the invention comprise alkylating agents, intercalating agents, metal coordination complexes, pyrimidine nucleosides, purine nucleosides, inhibitors of nucleic acid associated enzymes and proteins, and agents affecting structural proteins and cytoplasmic enzymes. The invention comprises the described methods as well as compositions and kits comprising a naphthalimide and an antiproliferative agent.

1 . A method of treatment of a host with a cellular proliferative disease, comprising contacting said host with a naphthalimide in conjunction with an antiproliferative agent, each in an amount sufficient to modulate said cellular proliferative disease, wherein said cellular proliferative disease is a solid tumor.  
   
   
       2 . The method according to  claim 1 , wherein said naphthalimide comprises amonafide and said antiproliferative agent is cisplastin.  
   
   
       3 . The method according to  claim 1 , wherein said naphthalimide comprises amonafide and said antiproliferative agent is 5-FU.  
   
   
       4 . The method according to  claim 1 , wherein said naphthalimide comprises amonafide and said antiproliferative agent is genistein.  
   
   
       5 . The method according to  claim 1 , wherein said naphthalimide comprises amonafide and said antiproliferative agent is rosmarinic acid.  
   
   
       6 . The method according to  claim 1 , wherein said naphthalimide comprises amonafide and said antiproliferative agent is camptothecin.  
   
   
       7 . The method according to  claim 1 , wherein said naphthalimide comprises an amonafide analog.  
   
   
       8 . The method according to  claim 1 , wherein said antiproliferative agent comprises an agent that interacts with nucleic acids.  
   
   
       9 . The method according to  claim 1 , wherein said antiproliferative agent comprises an alkylating agent, an intercalating agent, a metal coordination complex, a pyrimidine nucleoside, a purine nucleoside, an inhibitor of nucleic acid associated enzymes, or an inhibitor of nucleic acid associated proteins.  
   
   
       10 . The method according to  claim 1 , wherein said host is a human.  
   
   
       11 . The method according to  claim 1 , wherein said naphthalimide is administered before the administration of said antiproliferative agent.  
   
   
       12 . The method according to  claim 1 , wherein said naphthalimide is administered during the administration of said antiproliferative agent.  
   
   
       13 . The method according to  claim 1 , wherein said naphthalimide is administered after the administration of said antiproliferative agent.  
   
   
       14 . The method according to  claim 11 , wherein said naphthalimide is administered less than 4 hours before the administration of said antiproliferative agent.  
   
   
       15 . The method according to  claim 13 , wherein said naphthalimide is administered less than 4 hours after the administration of said antiproliferative agent.  
   
   
       16 . The method according to  claim 1 , wherein the modulation of said disease with said composition is greater than that for said antiproliferative agent alone.  
   
   
       17 . A composition comprising a naphthalimide and an antiproliferative agent, wherein said antiproliferative agent is genistein.  
   
   
       18 . A composition comprising a naphthalimide and an antiproliferative agent, wherein said antiproliferative agent is rosmarinic acid.  
   
   
       19 . A composition comprising a naphthalimide and an antiproliferative agent, wherein said antiproliferative agent is camptothecin.