Mithramycin oxime derivatives having increased selectivity and anti-cancer activity
Compounds described herein are mithramycin (MTM) oxide (OX) derivatives and MTM Hydrazine (HY) derivatives. These compounds are useful for treatment of cancers and neuro-diseases.
1. A compound having the following formula:
or a pharmaceutically acceptable salt thereof, wherein
R is
R 2 is OH, alkyl excluding methyl, alkylaryl, aryl, acyl, alkene, alkylalkene, alkyne, alkylalkyne, acyl, acylaryl, amino acid, amino acid dipeptide, acyl-amino acid, acyl-amino acid dipeptide, so long as R 2 is not CH 2 COOH;
R 3 is OH; and
X is O.
2. The compound of claim 1 , wherein R 2 is acylaryl, acyl-amino acid, or acyl-amino acid dipeptide.
3. The compound of claim 2 , wherein R 2 is acylaryl comprising a quinolone, a benzothizole, a phenyl, a pyridine, or an indol group.
4. The compound of claim 1 , wherein R 2 comprises a quinolone, a benzothizole, a phenyl, a pyridine, or an indol group.
5. The compound of claim 1 , wherein R 2 comprises an amino acid or amino acid dipeptide group, or a substituted amino acid or amino acid dipeptide group.
6. A compound having the following formula:
or a pharmaceutically acceptable salt thereof, wherein R is selected from the group consisting of:
7. A method of treating cancer or neuro-disease in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the compound of claim 1 .
8. The method of claim 7 , wherein the method comprises treating Ewing sarcoma.
9. The method of claim 7 , wherein the method comprises treating prostate cancer.
10. The method of claim 7 , wherein the method comprises treating colon cancer.
11. The method of claim 7 , wherein the method comprises treating lung cancer.
12. The method of claim 7 , wherein the method comprises treating leukemia or lymphoma.
13. A method for selectively modulating the activity of a target ETS transcription factor in a patient in need thereof, including administering to the patient a therapeutically effective amount of the compound of claim 1 .