Anti-cancer agents
Described herein are compounds that may be selectively activated to produce active anti-cancer agents in tumor cells. Also disclosed are pharmaceutical compositions comprising the compounds, and methods of treating cancer using the compounds.
1. A compound of formula (111a):
wherein:
each R 1 is independently selected from selected from the group consisting of:
each R 2 is independently selected from an electron-withdrawing group;
each X is independently halo;
each R 4 is independently selected from the group consisting of —H and —COO(alkyl), and
each R 5 is independently selected from optionally substituted alkyl;
wherein if the compound of formula (III) bears a positive charge, it further comprises at least one counterion Z ⊖ .
2. The compound of claim 1 , wherein each R 1 is —CH 2 X.
3. The compound of claim 2 , wherein each X is chloro.
4. The compound of claim 1 , wherein each R 1 is —CH(X)—R 4 .
5. The compound of claim 4 , wherein X is chloro.
6. The compound of claim 4 wherein R 4 is —C(O)OC(CH 3 ) 3 .
7. The compound of claim 1 , wherein each R 1 is —CH 2 —N(R a ) 3 ⊕ .
8. The compound of claim 7 , wherein each R a is methyl.
9. The compound of claim 1 , wherein each R 2 is independently selected from the group consisting of nitro, cyano and carboxy.
10. The compound of claim 1 , wherein each R 2 is nitro.
11. The compound of claim 1 , wherein the compound is selected from the group consisting of:
12. A method of treating cancer in a subject in need of treatment, comprising administering the subject a therapeutically effective amount of a compound of claim 1 , wherein the cancer is selected from the group consisting of leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer.
13. The method of claim 12 , wherein the subject is a human.
14. The method of claim 12 , further comprising administering an additional chemotherapeutic agent.
15. The method of claim 12 , further comprising administering radiation.
16. A method of reducing the proliferation of a cancer cell, comprising contacting the cancer cell with an effective amount of a compound of claim 1 , wherein the cancer cell is selected from the group consisting of leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer.