Delocalized lipophilic cation compounds and methods of use thereof
View Patent ↗Provided are delocalized lipophilic cation (DLC) compounds and methods of using such compounds. Also provided are pharmaceutical compositions that include a DLC compound. Provided methods include methods of killing cells and methods of fluorescently labeling mitochondria by contacting the cells with a DLC compound of the present disclosure. Also provided are methods of imaging cell mitochondria, methods of determining whether a patient has a mitochondria related disease, and methods of treating a patient for a mitochondria related disease. Kits that include compounds of the present disclosure are also provided.
1. A compound of formula (III):
wherein,
X − is a counterion;
R 1 and R 8 are each independently selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl;
R 2 and R 3 are each independently selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halogen, nitro and nitrile;
R 5 and R 6 are each independently selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halogen, nitro and nitrile; or R 5 and R 6 together with the carbon atoms to which they are attached form a fused ring selected from aryl, substituted aryl, heteroaryl and substituted heteroaryl;
R 4 is selected from substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, nitro and nitrile if R 6 is H; or R 4 is selected from H alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halogen, nitro and nitrile if R6 is not H and if R 4 is H or F then R 6 is not methyl; and
R 11 is selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl.
2. The compound of claim 1 , of the formula (IV):
wherein,
X − is a counterion;
R 1 is selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl;
R 2 and R 6 are each independently selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halogen, nitro and nitrile;
R 4 is selected from substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, nitro and nitrile if R 6 is H; or R 4 is selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halogen, nitro and nitrile if R 6 is not H;
and
R 11 is selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl.
3. The compound of claim 1 , selected from the structures:
4. The compound of claim 1 , wherein the compound is selectively cytotoxic to cancer cells.
5. A pharmaceutical composition, comprising:
a) a compound of claim 1 ; and
b) a pharmaceutically acceptable excipient.
6. A method of killing a cell, the method comprising contacting the cell with an effective amount of a compound of claim 1 .
7. A method of fluorescently labeling the mitochondria of a cell, the method comprising contacting the cell with an effective amount of a compound of claim 1 .
8. A kit comprising the compound of claim 1 .
9. The compound of claim 3 , wherein the compound is:
10. The compound of claim 4 , wherein the compound has an IC50 value of 10 μM or less.