Cytotoxin Compound And Method of Isolation

Abstract

The present invention concerns compounds derived from tunicates of the species Synoicum adareanum , as well as to pharmaceutical compositions comprising these compounds and methods of use. Extracts from tunicates show selective toxicity against several different cancer cell lines in the NCI 60 cell line panel. These compounds are useful in the effective treatment of cancers, particularly malignant melanomas, colon cancer, and renal cancer cell lines.

1 . A method of treating a subject with cancer or a cell proliferation disorder, comprising administering to the subject a therapeutically effective amount of at least one isolated compound obtained from extracts of a  Synoicum  species, or a composition comprising said compound. 
   
   
       2 . The method of  claim 1 , wherein said  Synoicum  species is  S. adareanum.    
   
   
       3 . The method of  claim 1 , wherein said isolated compound obtained from the  Synoicum  species is a Palmerolide. 
   
   
       4 . The method of  claim 3 , wherein said Palmerolide comprises the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, isomer, racemate, or racemic mixture thereof. 
   
   
       5 . The method of  claim 4 , wherein said salt is an acid salt of acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrochloride hydrobromide, hydroiodide, 2-hydroxyethane-sulfonate, lactate, maleate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, oxalate, thiocyanate, tosylate or undecanoate. 
   
   
       6 . The method of  claim 4 , wherein said salt is a base salt of ammonium salts, alkali metal salts, alkaline earth metal salts, salts with organic bases, N-methyl-D-glucamine, or salts with amino acids. 
   
   
       7 . The method of  claim 3 , wherein said Palmerolide comprises the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, isomer, racemate, or racemic mixture thereof. 
   
   
       8 . The method of  claim 7 , wherein said salt is an acid salt of acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrochloride hydrobromide, hydroiodide, 2-hydroxyethane-sulfonate, lactate, maleate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, oxalate, thiocyanate, tosylate or undecanoate. 
   
   
       9 . The method of  claim 7 , wherein said salt is a base salt of ammonium salts, alkali metal salts, alkaline earth metal salts, salts with organic bases, N-methyl-D-glucamine, or salts with amino acids. 
   
   
       10 . The method of  claim 3 , wherein said Palmerolide comprises the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, isomer, racemate, or racemic mixture thereof. 
   
   
       11 . The method of  claim 10 , wherein said salt is an acid salt of acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrochloride hydrobromide, hydroiodide, 2-hydroxyethane-sulfonate, lactate, maleate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, oxalate, thiocyanate, tosylate or undecanoate. 
   
   
       12 . The method of  claim 10 , wherein said salt is a base salt of ammonium salts, alkali metal salts, alkaline earth metal salts, salts with organic bases, N-methyl-D-glucamine, or salts with amino acids. 
   
   
       13 . The method of  claim 3 , wherein said Palmerolide comprises the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, isomer, racemate, or racemic mixture thereof. 
   
   
       14 . The method of  claim 13 , wherein said salt is an acid salt of acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrochloride hydrobromide, hydroiodide, 2-hydroxyethane-sulfonate, lactate, maleate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, oxalate, thiocyanate, tosylate or undecanoate. 
   
   
       15 . The method of  claim 13 , wherein said salt is a base salt of ammonium salts, alkali metal salts, alkaline earth metal salts, salts with organic bases, N-methyl-D-glucamine, or salts with amino acids. 
   
   
       16 . The method of  claim 1 , wherein the cancer is melanoma, colon cancer, or renal cancer. 
   
   
       17 . The method of  claim 1 , wherein said composition comprises a pharmaceutically acceptable carrier. 
   
   
       18 . The method of  claim 17 , wherein said pharmaceutically acceptable carrier comprises one or more of a diluent, excipient, wetting agent, buffering agent, suspending agent, lubricating agent, adjuvant, vehicle, delivery system, emulsifier, disintegrant, absorbent, preservative, surfactant, colorant, flavorant, or sweetener. 
   
   
       19 . The method of  claim 1 , wherein said compound or composition is administered to the subject parenterally, intravenously, intradermally, subcutaneously, orally, transdermally, topically, transmucosally, rectally, or by inhalation. 
   
   
       20 . The method of  claim 1 , wherein said compound or composition is provided as a controlled release formulation. 
   
   
       21 . A composition comprising an isolated compound obtained from extracts of a  Synoicum  species. 
   
   
       22 . The composition according to  claim 21 , wherein said compound comprises the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, isomer, racemate, or racemic mixture thereof. 
   
   
       23 . The composition according to  claim 21 , wherein said compound comprises the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, isomer, racemate, or racemic mixture thereof. 
   
   
       24 . The composition according to  claim 21 , wherein said compound comprises the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, isomer, racemate, or racemic mixture thereof. 
   
   
       25 . The composition according to  claim 21 , wherein said compound comprises the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, isomer, racemate, or racemic mixture thereof. 
   
   
       26 . A method for inhibiting the proliferation of a cell, comprising contacting said cell with an effective amount of an isolated compound obtained from extracts of a  Synoicum  species, or a composition comprising said compound. 
   
   
       27 . The method of  claim 26 , wherein said isolated compound is a Palmerolide. 
   
   
       28 . The method of  claim 26 , wherein said compound comprises the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, isomer, racemate, or racemic mixture thereof. 
   
   
       29 . The method of  claim 26 , wherein said compound comprises the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, isomer racemate, or racemic mixture thereof. 
   
   
       30 . The method of  claim 26 , wherein said compound comprises the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, isomer, racemate, or racemic mixture thereof. 
   
   
       31 . The method of  claim 26 , wherein said compound comprises the formula: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, isomer, racemate, or racemic mixture thereof. 
   
   
       32 . The method of  claim 26 , wherein said cell is a cancer cell. 
   
   
       33 . The method of  claim 32 , wherein said cancer cell is a melanoma cell, a colon cancer cell, or renal cancer cell.