Phenylahistin and the phenylahistin analogs, a new class of anti-tumor compounds

Abstract

Methods of using a compound, its pharmaceutically acceptable salts, and/or its pro-drug esters, in isolated form, to treat cancer, and methods for isolating, for formulating, and for administering the compound, salt, and/or pro-drug ester as an antitumor agent, wherein the compound, salt, or pro-drug ester has the following structure: wherein: R 1 , R 2 , R 5 , R 7 , and R 8 are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 24 alkyl, unsaturated C 1 -C 24 alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, substituted nitro, phenyl, and substituted phenyl groups, R 3 , R 4 , and R 6 are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 12 alkyl, unsaturated C 1 -C 12 alkenyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, and substituted nitro groups, X 1 and X 2 are separately selected from the group consisting of an oxygen atom, and a sulfur atom, and the dashed bond represents a bond selected from the group consisting of a carbon-carbon single bond and a carbon-carbon double bond. Most preferably, R 3 and R 4 are hydrogen, and each are involved in hydrogen bonds, and/or the dashed bond is a double bond, such that the chemical backbone of the compound substantially retains a substantially planar conformation.

1 . A method of preventing at least one fungal infection in a mammal afflicted with at least one fungal infection which comprises administering an antifungally effective amount of a compound sufficient for such treating or preventing, and wherein the compound has the following structure:  
     
       
         
         
             
             
         
       
       wherein:  
       R 1 , R 2 , R 5 , R 7 , and R 8  are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 24  alkyl, unsaturated C 1 -C 24  alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, substituted nitro, phenyl, and substituted phenyl groups,  
       R 3 , R 4 , and R 6  are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 12  alkyl, unsaturated C 1 -C 12  alkenyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, and substituted nitro groups,  
       X 1  and X 2  are separately selected from the group consisting of an oxygen atom, and a sulfur atom, and  
       the dashed bond represents a bond selected from the group consisting of a carbon-carbon single bond and a carbon-carbon double bond.  
     
   
   
       2 . The method of  claim 1 , wherein the fungal infection is selected from the group consisting of an Aspergillosis infection, blastomycosis infection, Candidiasis infection, Coccidioidomycosis infection, Cryptococcosis infection, Histopolasmosis infection, Paracoccidioidomycosis, Sporotrichosisand, and Mucormycosis infection.  
   
   
       3 . The method of  claim 2 , wherein the Aspergillosis infection is invasive pulmonary aspergillosis.  
   
   
       4 . The method of  claim 2 , wherein the Mucormycosis infection is craniofacial mucormycosis or pulmonary mucormycosis.  
   
   
       5 . The method of  claim 2 , wherein the Candidiasis infection is retrograde candidiasis of the urinary tract.  
   
   
       6 . A pharmaceutical composition for preventing fungal infection comprising an antifungally effective amount of a pharmaceutically acceptable carrier and a compound having the structure:  
     
       
         
         
             
             
         
       
       wherein:  
       R 1 , R 2 , R 5 , R 7 , and R 8  are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 24  alkyl, unsaturated C 1 -C 24  alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, substituted nitro, phenyl, and substituted phenyl groups,  
       R 3 , R 4 , and R 6  are each separately selected from the group consisting of a hydrogen atom, a halogen atom, and saturated C 1 -C 12  alkyl, unsaturated C 1 -C 12  alkenyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, nitro, and substituted nitro groups,  
       X 1  and X 2  are separately selected from the group consisting of an oxygen atom, and a sulfur atom, and  
       the dashed bond represents a bond selected from the group consisting of a carbon-carbon single bond and a carbon-carbon double bond.  
     
   
   
       7 . The composition of  claim 6 , wherein the fungal infection is selected from the group consisting of an Aspergillosis infection, blastomycosis infection, Candidiasis infection, Coccidioidomycosis infection, Cryptococcosis infection, Histopolasmosis infection, Paracoccidioidomycosis, Sporotrichosisand, and Mucormycosis infection.  
   
   
       8 . The composition of  claim 7 , wherein the Aspergillosis infection is invasive pulmonary aspergillosis.  
   
   
       9 . The composition of  claim 7 , wherein the Mucormycosis infection is craniofacial mucormycosis or pulmonary mucormycosis.  
   
   
       10 . The composition of  claim 7 , wherein the Candidiasis infection is retrograde candidiasis of the urinary tract.