Antileishmanial compositions and methods of use

Abstract

In one aspect, the invention relates methods and compositions for treating parasitic diseases, for example, leishmaniasis. In a further aspect, the compounds of the methods and compositions are isolated from Pentalinon andrieuxii . This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

What is claimed is: 
     
         1 . A method for the treatment of a parasitic disease in a mammal diagnosed with the disease, the method comprising the step of administering to the mammal a therapeutically effective amount of at least one compound having a structure represented by a formula: 
       
         
           
           
               
               
           
         
         wherein each ---- is independently an optional covalent bond, wherein valence is satisfied; 
         wherein R 1 , when present, is selected from C1-C12 alkyl and C1-C12 alkenyl; 
         wherein R 2 , when present, is selected from C1-C12 alkyl and C1-C12 alkenyl; 
         wherein R 7  is selected from hydrogen, hydroxyl, amino, and halogen; and 
         wherein R 8  is selected from hydrogen and C1-C6 alkyl; 
         or a pharmaceutically acceptable salt, solvate, or polymorph thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the parasitic disease is associated with infection of the mammal by  Leishmania  spp. 
     
     
         3 . The method of  claim 2 , wherein  Leishmania  spp. is selected from  Leishmania donovani, Leishmannia brasiliensis, Leishmania mexicana, Leishmania amazonensis, Leishmania aethiopica, Leishmania major, Leishmania chagasi, Leishmania panamensis, Leishmania infantum , and  Leishmania tropica.    
     
     
         4 . The method of  claim 1 , wherein the parasitic disease is a leishmaniases. 
     
     
         5 . The method of  claim 4 , wherein the leishmaniases is cutaneous leishmaniasis. 
     
     
         6 . The method of  claim 4 , wherein the leishmaniases is visceral leishmaniasis. 
     
     
         7 . The method of  claim 1 , wherein the mammal is human. 
     
     
         8 . The method of  claim 1 , wherein R 1  is selected from: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The method of  claim 1 , wherein R 2  is selected from: 
       
         
           
           
               
               
           
         
       
     
     
         10 . The method of  claim 1 , wherein the compound has a structure represented by a formula: 
       
         
           
           
               
               
           
         
         wherein each of R 4a  and R 4b  is independently selected from hydrogen and C1-C12 alkyl; 
         or a pharmaceutically acceptable salt, solvate, or polymorph thereof. 
       
     
     
         11 . The method of  claim 1 , wherein the compound has a structure represented by a formula: 
       
         
           
           
               
               
           
         
         wherein each of R 6a  and R 6b  is independently selected from hydrogen and C1-C12 alkyl; 
         or a pharmaceutically acceptable salt, solvate, or polymorph thereof. 
       
     
     
         12 . The method of  claim 1 , wherein the compound is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         13 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound represented by a formula: 
       
         
           
           
               
               
           
         
         wherein each ---- is independently an optional covalent bond, wherein valence is satisfied; 
         wherein R 1 , when present, is selected from C1-C12 alkyl and C1-C12 alkenyl; 
         wherein R 2 , when present, is selected from C1-C12 alkyl and C1-C12 alkenyl; 
         wherein R 7  is selected from hydrogen, hydroxyl, amino, and halogen; and 
         wherein R 8  is selected from hydrogen and C1-C6 alkyl; 
         or a pharmaceutically acceptable salt, solvate, or polymorph thereof. 
       
     
     
         14 . The composition of  claim 13 , wherein the pharmaceutically acceptable carrier is a liposome. 
     
     
         15 . The composition of  claim 14 , wherein the liposome comprises a phospholipid. 
     
     
         16 . The composition of  claim 14 , wherein the liposome comprises one or more lipids selected from phosphatidylcholine, tocopherol, cholesterol, and 1,2-distearoyl-phosphatidyl ethanolamine-methyl-polyethyleneglycol conjugate. 
     
     
         17 . The composition of  claim 14 , wherein the liposome comprises phosphatidylcholine and tocopherol. 
     
     
         18 . A kit comprising at least one compound represented by a formula: 
       
         
           
           
               
               
           
         
         wherein each ---- is independently an optional covalent bond, wherein valence is satisfied; 
         wherein R 1 , when present, is selected from C1-C12 alkyl and C1-C12 alkenyl; 
         wherein R 2 , when present, is selected from C1-C12 alkyl and C1-C12 alkenyl; 
         wherein R 7  is selected from hydrogen, hydroxyl, amino, and halogen; and 
         wherein R 8  is selected from hydrogen and C1-C6 alkyl; 
         or a pharmaceutically acceptable salt, solvate, or polymorph thereof, and one or more of: 
         a) at least one agent known to increase the likelihood of a parasitic disease in a mammal; 
         b) at least one agent known to decrease the likelihood of a parasitic disease in a mammal; 
         c) at least one agent known to treat a parasitic disease in a mammal; or 
         d) instructions for treating a parasitic disease. 
       
     
     
         19 . The kit of  claim 18 , wherein the at least one compound and the at least one agent are co-formulated. 
     
     
         20 . The kit of  claim 18 , wherein the at least one compound and the at least one agent are co-packaged.