Antibiotic sensitivity-restoring and photosensitive agents

Abstract

The present disclosure describes a method to treat conditions, including bacterial infections and cancer, using a photosensitive compound that, upon exposure to white light, can be activated. The photosensitive compound can also interact synergistically with antibiotics used concomitantly to kill drug-resistant bacteria. The photosensitive compounds can also be used to inhibit the proliferation of cancer cells.

1 - 52 . (canceled) 
     
     
         53 . A method of treating a condition, the method comprising administering to a subject in need thereof a therapeutically-effective amount of a compound and a therapeutically-effective amount of a second agent, wherein the compound is of the formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is hydrogen or an ester group; 
 R 2  is hydrogen, halogen, or L 1 -Ar 1 ; 
 R 3  is hydrogen, halogen, or L 2 -Ar 2 ; 
 each L 1  and L 2  is independently alkylene, alkenylene, O, S, SO 2 , CO, N 2  or a bond; 
 Ar 1  is a substituted or unsubstituted aryl group; 
 Ar 2  is a substituted or unsubstituted aryl group wherein Ar 2  is not substituted with an amide, amine, nitro, imine, or ester group; 
 each A 1 , A 2 , A 3 , and A 4  is independently C(R 1a ), C(R 1a )(R 1b ), N, or N(R 1a ); 
 each R 1a  and R 1b  is independently hydrogen, halogen, hydroxyl, sulfhydryl, nitro, nitroso, cyano, azido, a sulfoxide group, a sulfone group, a sulfonamide group, a sulfonic acid group, an imine group, an acyl group, an acyloxy group, alkyl, alkenyl, alkynyl, an alkoxy group, an ether group, a carboxylic acid group, a carboxaldehyde group, an ester group, an amine group, an amide group, a carbonate group, a carbamate group, a thioether group, a thioester group, a thioacid group, aryl, aryloxy, arylalkyl, arylalkoxy, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl, any of which is substituted or unsubstituted; and 
 each   is independently a single or double bond, 
 
       or a pharmaceutically-acceptable salt thereof, wherein the compound is not: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         54 . The method of claim  1 , wherein the compound is of the formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is hydrogen; 
 R 2  is hydrogen or L 1 -Ar 1 ; 
 R 3  is L 2 -Ar 2 ; and 
 each A 1 , A 2 , A 3 , and A 4  is independently C(R 1a ) or N, 
 
       or a pharmaceutically-acceptable salt thereof. 
     
     
         55 . The method of  claim 53 , further comprising irradiating the compound with light having a wavelength of about 200 nm to about 800 nm. 
     
     
         56 . The method of  claim 53 , wherein the condition is an infection. 
     
     
         57 . The method of  claim 56 , wherein the infection is caused by a microbe. 
     
     
         58 . The method of  claim 57 , wherein the microbe is a bacterium. 
     
     
         59 . The method of  claim 57 , wherein the microbe is a Gram-positive bacterium. 
     
     
         60 . The method of  claim 57 , wherein the microbe is a Gram-negative bacterium. 
     
     
         61 . The method of  claim 57 , wherein the microbe is a drug resistant bacterium. 
     
     
         62 . The method of  claim 57 , wherein the microbe is methicillin-resistant  Staphylococcus aureus.    
     
     
         63 . The method of  claim 57 , wherein the microbe is  Acinetobacter baumannii.    
     
     
         64 . The method of  claim 53 , wherein the compound binds a biological structure. 
     
     
         65 . The method of  claim 64 , wherein the biological structure is an efflux pump. 
     
     
         66 . The method of  claim 53 , wherein the compound decreases an activity of a drug resistance mechanism in a microbe. 
     
     
         67 . The method of  claim 53 , wherein the second agent is polymyxin B or a pharmaceutically-acceptable salt thereof. 
     
     
         68 . The method of  claim 53 , wherein the compound and the second agent are administered in a common unit dosage form. 
     
     
         69 . The method of  claim 53 , wherein the administration is oral. 
     
     
         70 . The method of  claim 53 , wherein the administration is intravenous. 
     
     
         71 . The method of  claim 53 , wherein the administration is subcutaneous. 
     
     
         72 . The method of  claim 53 , wherein the administration is topical.