Dual small molecule inhibitors of cancer and angiogenesis

1. A method of treating cancer in a subject in need thereof, said method comprising administering to said subject a pharmaceutical composition comprising a therapeutically effective amount of at least one compound of having the general structure of formula I,

wherein R 1 , R 3 , and R 4 are independently selected from the group consisting of NO 2 , H, halo, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 5 -C 7 aryl, mono-, di- or tri-chloro, and mono-, di- or tri-methyl, R 2 is H, or R 3 and R 2 taken together with the atoms to which they are attached form an optionally substituted heterocyclic fused ring, or R 3 and R 4 taken together with the atoms to which they are attached form an optionally substituted cycloalkyl fused ring;

X is selected from the group consisting of NR 5 , and —(NH(CH 2 ) n )—; wherein n is 1 or 2;

Z is selected from the group consisting of a bond, CO, C 1 -C 4 alkyl, C 1 -C 4 alkenyl, and C 1 -C 4 alkynyl; and

R 5 is H, or R 3 and R 5 taken together with the atoms to which they are attached form an optionally substituted heterocyclic fused ring;

thereby treating cancer in a subject; and

wherein said cancer is colorectal cancer.

2. A method of treating cancer in a subject in need thereof, said method comprising administering to said subject a pharmaceutical composition comprising a therapeutically effective amount of at least one compound having the general structure,

wherein R 1 , R 3 and R 4 are independently selected from the group consisting of H, halo and C 1 -C 4 alkyl; and

R 2 and R 5 are H;

thereby treating cancer in a subject; and

wherein said cancer is colorectal cancer.

3. The method of claim 2 , wherein said subject is a human.

4. The method of claim 1 , wherein said subject is a human.

5. The method of claim 1 , wherein said at least one compound disrupts β-tubulin polymerization.

6. The method of claim 1 , wherein said at least one compound inhibits angiogenesis.

7. The method of claim 1 , wherein said at least one compound inhibits a P glycoprotein mediated multi-drug resistant cancer.

8. The method of claim 1 , wherein said cancer comprises a mutant p53 protein.

9. The method of claim 1 , wherein said pharmaceutical composition is administered via a route selected from the group consisting of topical, oral, buccal, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, sublingual, vaginal, ophthalmic, pulmonary, and rectal.

10. The method of claim 1 , wherein said pharmaceutical composition further comprises a therapeutically effective amount of a known chemotherapeutic agent.

11. The method of claim 1 , wherein said at least one compound inhibits cancer cell proliferation.

12. The method of claim 1 , wherein said at least one compound inhibits endothelial cell proliferation.

13. The method of claim 1 , wherein said compound having the general structure of formula I is

14. The method of claim 1 , wherein said compound having the general structure of formula I is selected from the group consisting of:

wherein R 1 is 2-Cl, 2-CH 3 , 3-Cl, 3-CH 3 , 4-Cl or 4-CH 3 ;

wherein n is 1 or 2;

wherein Z is CO, —CH 2 —, or —C 2 H 4 —;

wherein n is 1 or 2;

wherein R 3 is 2-Cl and R 4 is H, R 3 is 3-Cl and R 4 is H, R 3 is 2-CH 3 and R 4 is H, R 3 is 3-CH 3 and R 4 is H, R 3 is H and R 4 is 2,3,4-trichloro, or R 3 is H and R 4 is 2,3,4-trimethyl;

15. The method of claim 1 , wherein;

R 1 , R 3 and R 4 are independently selected from the group consisting of H, halo, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl and C 5 -C 6 aryl;

X is selected from the group consisting of NR 5 , and —(NH(CH 2 ) n ); wherein n is 1 or 2;

Z is selected from the group consisting of a bond, and CO; and

R 2 and R 5 are independently selected from the group consisting of H, halo, C 5 -C 6 aryl, C 1 -C 4 alkyl, C 1 -C 4 alkenyl, and C 1 -C 4 alkynyl.

16. The method of claim 1 , wherein;

R 1 , R 3 and R 4 are independently selected from the group consisting of H, halo and C 1 -C 4 alkyl;

X is NR 5 ;

Z is selected from the group consisting of a bond and CO; and

R 2 and R 5 are H.

17. The method of claim 1 , wherein the pharmaceutical composition comprises a pharmaceutically-acceptable carrier and a compound having the general structure of:

wherein R 1 , R 3 and R 4 are independently selected from the group consisting of H, halo and C 1 -C 4 alkyl;

X is NR 5 ; and

R 2 and R 5 are H.

18. The method of claim 1 , wherein the pharmaceutical composition comprises a pharmaceutically-acceptable carrier and a compound having the general structure of:

wherein R 1 , R 3 and R 4 are independently selected from the group consisting of H, halo and C 1 -C 4 alkyl;

X is NR 5 ; and

R 2 and R 5 are H.

19. The method of claim 1 , wherein the colorectal cancer is an adenocarcinoma.