Antifungal and antiparasitic polyene macrolides

Abstract

In certain aspects, the present disclosure provides for novel, water-soluble polyene macrolides and salts or solvates thereof and methods of making the water-soluble polyene macrolides. Also provided are compositions and methods for inhibiting, preventing, and/or treating fungal and parasitic diseases in a subject.

1 - 27 . (canceled) 
     
     
         28 . A method of treating or inhibiting a parasitic infection in a subject, the method comprising administering to the subject an effective amount of a compound of Structure (III): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable isomer thereof, wherein:
 X is sodium. 
 
     
     
         29 - 36 . (canceled) 
     
     
         37 . The method of  claim 28 , wherein the parasitic infection is a protozoal infection. 
     
     
         38 . The method of  claim 37 , wherein the parasitic infection is leishmaniasis. 
     
     
         39 . The method of  claim 38 , wherein the parasitic infection is visceral leishmaniasis. 
     
     
         40 . The method of  claim 38 , wherein the parasitic infection is cutaneous leishmaniasis. 
     
     
         41 . The method of  claim 37 , wherein the parasitic infection is primary amoebic meningoencephalitis. 
     
     
         41 - 49 . (canceled) 
     
     
         51 . The method of  claim 28  the compound has Structure (IV): 
       
         
           
           
               
               
           
         
       
     
     
         51 - 63 . (canceled) 
     
     
         65 . A pharmaceutical composition comprising a compound having Structure (III) 
       
         
           
           
               
               
           
         
       
       wherein X is sodium together with one or more pharmaceutically acceptable vehicle(s). 
     
     
         66 . The pharmaceutical composition of  claim 65 , wherein the pharmaceutically acceptable excipient is a permeation enhancer excipient. 
     
     
         66 - 67 . (canceled) 
     
     
         69 . The pharmaceutical composition of  claim 65 , wherein the pharmaceutical composition further comprises a polycation that is chitosan, a quaternary ammonium derivative of chitosan, poly-L-arginine, aminated gelatin, dimethylaminoethyl methacrylate-methyl methacrylate copolymer, a polyvinyl acetal diethylaminoacetate, or a combination thereof. 
     
     
         70 . The pharmaceutical composition of  claim 69 , wherein the polycation is chitosan. 
     
     
         70 - 73 . (canceled) 
     
     
         75 . The pharmaceutical composition of  claim 65 , wherein the pharmaceutically acceptable vehicle comprises glutathione. 
     
     
         75 - 94 . (canceled) 
     
     
         96 . The method of  claim 28 , wherein the parasitic infection is a fungal infection.