Small molecules for treating cancer, inhibiting chemokine activity and/or inducing cell death
Compounds capable of, or usable in, inducing death of cancer cells and/or modulating a biological activity of a chemokine e.g., cell migration, and/or treating diseases and disorders associated with a biological activity of a chemokine and/or cell migration, and/or in treating cancer, are provided herein. The compounds are collectively represented by Formulae Ia or Ib: wherein A, B, D, E, G and R 1 -R 5 are as defined in the specification, with one or more of D, E and G, preferably E, is hydroxy.
1. A compound represented by Formula Ia and/or Ib:
wherein:
A is an alkyl being at least 4 carbon atoms in length;
B is selected from hydroxy and alkoxy;
D and G are each independently selected from hydrogen, hydroxy, alkoxy and alkyl, provided that at least one of D and G is hydrogen;
E is hydroxy;
R 1 is selected from hydrogen and alkyl; and
each of R 2 -R 5 is independently selected from hydrogen, hydroxy, halo, alkoxy, thioalkoxy, thiol, thioalkoxy and amine.
2. The compound of claim 1 , wherein B is alkoxy.
3. The compound of claim 1 , wherein one of D and G is alkoxy.
4. The compound of claim 1 , wherein when one of D and G is alkyl, said alkyl is at least 4 carbon atoms in length.
5. The compound of claim 1 , wherein each of R 1 -R 5 is hydrogen.
6. The compound of claim 1 , represented by Formula IIa or IIb:
wherein:
A is an alkyl being at least 4 carbon atoms in length;
B is selected from hydroxy and alkoxy;
D and G are each independently selected from hydrogen, hydroxy, alkoxy and alkyl, provided that at least one of D and G is hydrogen;
R 1 is selected from hydrogen and alkyl; and
each of R 2 -R 5 is independently selected from hydrogen, hydroxy, halo, alkoxy, thioalkoxy, thiol, thioalkoxy and amine.
7. The compound of claim 6 , wherein each of R 1 -R 5 is hydrogen.
8. The compound of claim 6 , wherein at least one of D and G is alkoxy.
9. The compound of claim 6 , wherein B is alkoxy.
10. The compound of claim 1 , being:
11. The compound of claim 1 , being capable of inducing cells death and/or of inducing apoptosis in cells.
12. The compound of claim 11 , wherein said cells are cancer cells.
13. The compound of claim 12 , wherein said cancer cells are drug-resistant cancer cells.
14. The compound of claim 1 , being capable of inducing arrest of cancer cell growth at the G2M phase of cancer cells.
15. The compound of claim 1 , being capable of inhibiting chemokine-induced cell migration.
16. A method of treating cancer in a subject in need thereof the method comprising administering to the subject a therapeutically effective amount of the compound of claim 1 .
17. The method of claim 16 , wherein said cancer is selected from a leukemia, a melanoma, a lung cancer, a lymphoma, a myeloma, a pancreatic cancer, an ovarian cancer, a liver cancer, a brain cancer, a colorectal cancer and a prostate cancer.
18. The method of claim 16 , wherein said cancer is characterized by expression of CXCR4.
19. The method of claim 16 , wherein said cancer is a drug-resistant cancer.
20. The method of claim 16 , further comprising administering to the subject an additional anti-cancer agent.
21. A method of modulating a biological activity of a chemokine in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound of claim 1 .
22. The method of claim 21 , being for treating a condition treatable by modulating said biological activity of said chemokine.
23. The method of claim 22 , wherein said chemokine is SDF-1.
24. A method of inducing cell death and/or of inducing apoptosis in cells, the method comprising contacting the cell with the compound of claim 1 .
25. The method of claim 24 , wherein said cells are cancer cells.
26. The method of claim 24 , wherein said cells are drug-resistant cells.
27. A method of inducing arrest of cancer cell growth at the G2M phase of cancer cells the method comprising contacting the cancer cells with the compound of claim 1 .