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US 2025/0057959 A1Published application
Phosphane gold(i)-n-heterocyclic carbene complexes for treating cancer
AssigneeKing Fahd University of Petroleum and Minerals
InventorsAdam Ahmed Abdallah SULAIMAN, Anvarhusien A. ISAB
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Abstract
A complex for treating a cancer includes gold, a 1,3-bis(2,6-di-isopropylphenyl)imidazole-2-ylidene ligand, and at least one phosphane ligand selected from the group consisting of bis(2-cyanoethyl)phenylphosphane, (1R,2R)-2-diphenylphosphano)-1 aminocyclohexane, (1R,2R)-2-diphenylphosphano)-1,2-diphenylethylamine, (R)-2 (diphenylphosphano)-1-phenylethylamine, (R)-1-(diphenylphosphano)-2-amino-3,3 dimethylbutane, tricyclohexylphosphane, and 3-(diphenylphosphano)propylamine), wherein the 1,3-bis(2,6-di-isopropylphenyl)imidazole-2-ylidene ligand and the at least one phosphane ligand are bonded to the gold.
Claims20
1:
- A complex, comprising:
- gold;
- a 1,3-bis(2,6-di-isopropylphenyl)imidazole-2-ylidene ligand;
- and at least one phosphane ligand selected from the group consisting of bis(2-cyanoethyl)phenylphosphane, (1R,2R)-2-diphenylphosphano)-1-aminocyclohexane, (1R,2R)-2-diphenylphosphano)-1,2-diphenylethylamine, (R)-2-(diphenylphosphano)-1-phenylethylamine, (R)-1-(diphenylphosphano)-2-amino-3,3-dimethylbutane, tricyclohexylphosphane, and 3-(diphenylphosphano)propylamine),
- wherein the 1,3-bis(2,6-di-isopropylphenyl)imidazole-2-ylidene ligand and the at least one phosphane ligand are bonded to the gold.
2 more elements
2:
- The complex of claim 1, wherein the phosphane ligand is tricyclohexylphosphane.
3:
- The complex of claim 1, having a half maximal inhibitory concentration of 0.1 to 2.5 μM in a first ovarian cancer cell line, A2780.
4:
- The complex of claim 1, having a half maximal inhibitory concentration of 0.1 to 4.0 μM in a first ovarian cancer cell line resistant to cisplatin, A2780cis.
5:
- The complex of claim 1, having a fold resistance of 0.5 to 2, wherein the fold resistance is based on a ratio of a half maximal inhibitory concentration in the first ovarian cancer cell line resistant to cisplatin, A2780cis, to a half maximal inhibitory concentration in the first ovarian cancer cell line, A2780.
6:
- The complex of claim 2, having a half maximal inhibitory concentration of 0.10 to 0.20 μM in the first ovarian cancer cell line, A2780.
7:
- The complex of claim 2, having a half maximal inhibitory concentration of 0.10 to 0.15 μM in the first ovarian cancer cell line resistant to cisplatin, A2780cis.
8:
- The complex of claim 2, having a fold resistance of less than 1, wherein the fold resistance is based on a ratio of a half maximal inhibitory concentration in the first ovarian cancer cell line resistant to cisplatin, A2780cis, to a half maximal inhibitory concentration in the first ovarian cancer cell line, A2780.
9:
- The complex of claim 2, having a half maximal inhibitory concentration of 0.55 to 0.65 μM in a second ovarian cancer cell line, SKOV3.
10:
- A pharmaceutical composition comprising the complex of claim 1 in an amount effective for treating a patient having ovarian cancer, and at least one pharmaceutical additive or adjuvant.
11:
- The complex of claim 1, made by a process comprising:
- mixing a silver hexafluorophosphate salt in a polar protic solvent with a 1,3-bis(2,6-diisopropylphenyl-imidazole-2-ylidene) gold chloride salt in a polar aprotic solvent to form a reaction mixture;
- reacting the reaction mixture with the phosphane ligand in a polar aprotic solvent to form the complex,
- wherein the silver hexafluorophosphate salt, the 1,3-bis(2,6-diisopropylphenyl-imidazole-2-ylidene) gold chloride salt, and the phosphane ligands are in an equimolar amount.
1 more element
12:
- A method for treating ovarian cancer, comprising:
- administering the complex of claim 2 to a patient in need of treatment for ovarian cancer,
- wherein during the administering the complex is contacted with an ovarian cancer in the form of at least one of a monolayer of cells, a multicellular tumor spheroid (MCTS), and an in vivo xenograft tumor.
13:
- The method of claim 12, wherein administering the complex induces apoptosis in A2780, A2780cis, and a multicellular tumor spheroid sample of the second ovarian cancer cell line, SKOV3.
14:
- The method of claim 12, wherein the complex administered at a concentration of 1 μM decreases the volume of SKOV3-MCTSs by 85 to 95% based on volume after 7 days.
15:
- The method of claim 12, wherein the complex administered at a concentration of 0.50 μM generates mitochondrial reactive oxygen species (mitROS) in SKOV3-MCTSs of 50 to 60% based on a cell count after 24 hours.
16:
- The method of claim 12, wherein the complex administered to the sample at a concentration of 0.1 to 0.6 μM has an amount of cells in the S phase from 15 to 35% compared to the sample in the absence of the complex having an amount of cells in the S phase from 40 to 50% based on a cell count after a time of 24 hours.
17:
- The method of claim 12, wherein the complex administered to the sample at a concentration of 0.1 to 0.6 μM has an amount of cells in the G1 phase from 60 to 80% compared to the sample in the absence of the complex having an amount of cells in the G1 phase from 45 to 55% based on a cell count after a time of 24 hours.
18:
- The method of claim 12, wherein the complex administered to the sample at a concentration of 0.5 μM decreases a proteasome activity by 30 to 70% after 24 hours based on a 20S-proteasome assay compared to the sample in the absence of the complex.
19:
- The method of claim 12, wherein the sample is in vivo xenograft tumor and the complex administered to the sample showed a reduction of the sample of more than 80% based on sample volume after 35 days of a treatment of 2 milligrams of the complex per kilogram of a body weight of a host of the sample two times a week.
20:
- A pharmaceutical composition comprising the complex of claim 1 or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent, or excipient.