Gold(i) complexes with anticancer properties and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2017232012-A1
Application number	US-201715586333-A
Country	US
Kind code	A1
Filing date	May 4, 2017
Priority date	Jan 7, 2016
Publication date	Aug 17, 2017
Grant date	—

Abstract

Monomeric and dimeric gold(I) complexes as anticancer agents. The gold(I) complexes are coordinated to mixed ligands: one phosphine-based ligand that may be monodentate or bidentate and at least one dithiocarbamate-based ligand that is monodentate. Pharmaceutical compositions incorporating the gold(I) complexes, methods of synthesis, methods of treating cancer and methods of inhibiting cancer cell proliferation and inducing cancer cell apoptosis are also provided.

First claim

1 - 7 . (canceled)

8 . A method for inhibiting proliferation of cancer cells, comprising:
contacting the cancer cells with a cytotoxic effective amount of a gold(I) complex represented by Formula (1) or Formula (2) or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein the cancer cells are at least one selected from the group consisting of prostate cancer cells and gastrointestinal cancer cells, and Formula (1) and Formula (2) are:

where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 are each independently a linear or branched, substituted or unsubstituted C 1 -C 8 alkyl group or a substituted or unsubstituted C 6 -C 8 aryl group; and
R 14 is a methylene group or —CH 2 —CH 2 —.

9 . The method of claim 8 , wherein the cancer cells are human cells.

10 . (canceled)

11 . The method of claim 8 , wherein the cytotoxic effective amount of the gold(I) complex is from 5 to 50 μM.

12 . The method of claim 8 , wherein the gold(I) complex exhibits an IC 50 from 1 to 150 μM for inhibiting the proliferation and inducing the apoptosis of the cancer cells.

13 . The method of claim 8 , wherein the cancer cells are prostate cancer cells and are at least one selected from the group consisting of PC-3 cells and DU-145 cells.

14 . The method of claim 8 , wherein cancer cells are gastrointestinal cancer cells and are SGC7907 cells.

15 . The method of claim 8 , wherein:
R 1 , R 2 and R 3 are each selected from the group consisting of a methyl group, an ethyl group, a propyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isopropyl group, a neopentyl group, a sec-pentyl group; a tert-pentyl group, an n-hexyl group, an isohexyl group, and a neohexyl group; R 4 and R 5 are each selected from the group consisting of a methyl group, an ethyl group, a phenyl group, and a benzyl group; R 6 , R 7 , R 8 and R 9 are each selected from the group consisting of a phenyl group and a benzyl group; R 10 , R 11 , R 12 and R 13 are each selected from the group consisting of a methyl group, an ethyl group, a phenyl group and a benzyl group; and R 14 is a methylene group or —CH 2 —CH 2 —.

16 . The method of claim 8 , wherein the gold(I) complex has a formula selected from the group consisting of Formula (3), Formula (4), Formula (5), and Formula (6):

Assignees

• Univ King Fahd Pet & Minerals

Inventors

• Altaf Muhammad
• Monim-Ul-Mehboob Muhammad
• Isab Anvarhusein Abdulkadir
• Altuwaijri Saleh

Classifications

• A61K31/66 Primary

  Phosphorus compounds · CPC title

• A61K33/242

  Gold; Compounds thereof · CPC title

• C07F9/5045

  Complexes or chelates of phosphines with metallic compounds or metals · CPC title

• C07F1/12

  Gold compounds · CPC title

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title