Inhibitors of oxidized low-density lipoprotein receptor 1 and methods of use thereof
Inhibitors of oxidized low-density lipoprotein receptor 1 (LOX-1), compositions comprising inhibitors of LOX-1, and methods of using thereof are described.
1. A method of inhibiting oxidized low-density lipoprotein receptor 1 (LOX-1) in a cell, the method comprising contacting the cell with an effective amount of a compound having a structure represented by a formula:
wherein:
X is selected from the group consisting of oxygen, sulfur, sulfoxide, sulfone, and NH;
R 1 is selected from the group consisting of hydrogen, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, aryl, halogen, aminoalkyl, amino, phosphoro, sulfhydryl, sulfino, sulfo, and cyano;
R 2 is selected from the group consisting of hydrogen, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, unsubstituted aryl, halogen, aminoalkyl, amino, phosphoro, sulfhydryl, sulfino, sulfo, and cyano;
R 3 is selected from the group consisting of hydrogen, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, aryl, halogen, aminoalkyl, amino, phosphoro, sulfhydryl, sulfino, sulfo, and cyano;
R 5 is hydroxyl; and
each of R 6 , R 7 , R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, aryl, halogen, phosphoro, sulfhydryl, sulfino, sulfo, and cyano, thereby inhibiting oxidized LOX-1.
2. The method of claim 1 , wherein X is oxygen.
3. The method of claim 1 , wherein R 1 is selected from the group consisting of hydrogen, amino, and C1-C5 alkyl.
4. The method of claim 1 , wherein R 2 is selected from the group consisting of hydrogen and C1-C5 alkyl.
5. The method of claim 1 , wherein R 3 is selected from the group consisting of hydrogen, C1-C5 alkyl, cyano, and halogen.
6. A method of inhibiting oxidized low-density lipoprotein receptor 1 (LOX-1) in a cell, the method comprising contacting the cell with an effective amount of a compound selected from:
thereby inhibiting oxidized LOX-1.
7. The method of claim 1 , wherein the compound is:
8. The method of claim 1 , wherein the cell is human.
9. The method of claim 1 , wherein the cell has been isolated from a subject prior to the administering step.
10. The method of claim 1 , wherein contacting is via administration to a subject.
11. The method of claim 10 , wherein the subject has been diagnosed with a need for treatment of a disorder associated with LOX-1 activity or elevated levels of ox-LDL.