ROS-activated compounds as selective anti-cancer therapeutics
Provided are compounds according to the following Formula I: The Formula I compounds are activated in the presence of reactive oxygen species (ROS) and are therefore selective anti-cancer therapeutics for cancers associated with elevated ROS. Also provided are methods and pharmaceutical compositions for treating cancers associated with increased ROS.
1. A compound according to Formula I:
wherein:
R 1 and R 2 are each independently selected from the group consisting of substituted or unsubstituted or branched alkyl and unsubstituted aryl wherein said alkyl and aryl optionally comprise one or more heteroatoms;
R 3 is selected from the group consisting of OH, NHC(O)CH 3 , piperidine and OC(O)CH 3 ; and n is 1-5,
wherein at least one of R 1 and R 2 is aryl.
2. The compound according to claim 1 , wherein alkyl substitutions are selected from the group consisting of alkoxyl, halo, OH, CN, carboxyl, carboxyl ester, and substituted or unsubstituted alkyl.
3. The compound according to claim 1 , wherein R 1 is alkyl when R 2 is aryl, and wherein R 2 is alkyl when R 1 is aryl.
4. The compound according to claim 1 , wherein R 1 and R 2 are each independently selected from the group consisting of substituted or unsubstituted C 1 -C 8 alkyl and unsubstituted phenyl; and R 3 is OH.
5. The compound according to claim 1 , wherein the compound is
6. A pharmaceutical composition for the treatment of a cancer associated with elevated ROS comprising:
(a) a therapeutically effective amount of a compound according to claim 1 ; and
(b) a pharmaceutically-acceptable carrier.
7. A compound selected from the group consisting of:
4-(2-(methyl(phenyl)amino)ethoxy)phenol;
4-(2-(ethyl(phenyl)amino)ethoxy)phenol;
4-(2-(isopropyl(phenyl)amino)ethoxy)phenol;
4-(3-(methyl(phenyl)amino)propoxy)phenol;
4-(3-(ethyl(phenyl)amino)propoxy)phenol;
4-(4-(methyl(phenyl)amino)butoxy)phenol;
4-(4-(ethyl(phenyl)amino)butoxy)phenol;
4-(5-(methyl(phenyl)amino)pentyloxy)phenol;
4-((5-(methyl(phenyl)amino)pentyl)oxy)phenol;
4,4′-(2,2′-(phenylazanediyl)bis(ethane-2,1-diyl)bis(oxy))diphenol; and
(((phenylazanediyl)bis(ethane-2,1-diyl))bis(oxy))bis(4,1-phenylene) diacetate.