Potent indole-3-carbinol-derived antitumor agents
View Patent ↗Compounds and methods for treating cancer and inducing apoptosis in unwanted rapidly proliferating cells. The compounds are shown in formula I: wherein X is hydroxyl or amino; Y is carboxyl or sulfonyl; R 1 , R 2 , R 3 , and R 4 can be the same or different and are selected from hydrogen, halogen, methoxy, trifluoromethyl, hydroxyl and combinations thereof, R 5 , R 6 , and R 7 may be the same or different and are selected from hydrogen, chloro, bromo, nitro, phenyl, amino, methoxy, and combinations thereof, and derivatives or metabolites thereof.
1. A compound of formula I:
wherein
X is selected from hydroxyl and amino;
Y is carboxyl;
R 1 , R 2 , R 3 , and R 4 are selected from hydrogen, halogen, methoxy, trifluoromethyl, hydroxyl and combinations thereof; and
R 5 , R 6 , and R 7 are selected from hydrogen, chloro, bromo, nitro, phenyl, amino, methoxy, and combinations thereof.
2. The compound of claim 1 , wherein R 1 , R 2 , R 3 , and R 4 are hydrogen, and X is hydroxyl.
3. The compound of claim 2 , wherein the compound is selected from:
4. A compound selected from:
5. The compound of claim 1 , wherein R 1 , R 2 , R 3 , and R 4 are hydrogen, and X is amino.
6. The compound of claim 5 , wherein the compound is selected from:
7. A compound selected from:
8. The compound of claim 1 , wherein R 5 is hydrogen, R 6 is nitro, R 7 is chloro, and X is hydroxyl.
9. The compound of claim 8 , wherein the compound is selected from:
10. A compound of formula I:
wherein X is hydroxy; Y is sulfonyl;
R 1 , R 2 , R 3 , and R 4 are selected from hydrogen, halogen, methoxy, trifluoromethyl, hydroxyl and combinations thereof;
R 5 is hydrogen, R 6 is nitro, and R 7 is chloro.
11. The compound of claim 10 , wherein the compound is selected from:
12. The compound of claim 1 , wherein R 5 is hydrogen, R 6 is nitro, R 7 is chloro, and X is amino.
13. The compound of claim 12 , wherein the compound is selected from:
14. A compound of formula I:
wherein X is amino; Y is sulfonyl;
R 1 , R 2 , R 3 , and R 4 are selected from hydrogen, halogen, methoxy, trifluoromethyl, hydroxyl and combinations thereof;
R 5 is hydrogen, R 6 is nitro, and R 7 is chloro.
15. The compound of claim 14 , wherein the compound is selected from:
16. A method of inducing apoptosis in rapidly proliferating cells, the method comprising the steps of contacting the rapidly proliferating cells with an effective amount of a compound of formula I:
wherein
X is selected from hydroxyl and amino;
Y is selected from carboxyl and sulfonyl;
R 1 , R 2 , R 3 , and R 4 are selected from hydrogen, halogen, methoxy, trifluoromethyl, hydroxyl and combinations thereof; and
R 5 , R 6 , and R 7 are selected from hydrogen, chloro, bromo, nitro, phenyl, amino, methoxy, and combinations thereof.
17. The method of claim 16 , wherein the rapidly proliferating cells are in vitro cells.
18. The method of claim 16 , wherein the rapidly proliferating cells are prostate cancer cells.
19. A method for treating, inhibiting, or delaying the onset of cancer in a subject in need of such treatment, wherein the method comprises administering a therapeutically effective amount of a compound of formula I:
wherein
X is selected from hydroxyl and amino;
Y is selected from carboxyl and sulfonyl;
R 1 , R 2 , R 3 , and R 4 are selected from hydrogen, halogen, methoxy, trifluoromethyl, hydroxyl and combinations thereof; and
R 5 , R 6 , and R 7 are selected from hydrogen, chloro, bromo, nitro, phenyl, amino, methoxy, and combinations thereof; to the subject in need of such treatment, wherein the cancer is prostate cancer.