Phosphinogold(I) complexes and methods of treating cancer
Mixed ligand phosphinogold(I) complexes as anticancer agents. The gold(I) ion of the complexes is coordinated to a phosphine and a dithiocarbamate or halogen ligand. Also described are a pharmaceutical composition incorporating the phosphinogold(I) complex, a method of synthesizing the phosphinogold(I) complex, and a method of treating cancer. The phosphinogold(I) complexes exhibit potent cytotoxicity against lung, cervical, and liver cancer cells.
1. A gold(I) complex of formula (I)
or a salt thereof, a solvate thereof, a tautomer thereof, a stereoisomer thereof, or a mixture thereof,
wherein:
R 1 and R 2 are each independently an optionally substituted aryl;
R 3 is selected from the group consisting of —OH, —OCH 3 , —NH 2 , and —N(CH 3 ) 2 ;
R 4 is a halogen or
and
n is an integer in a range of 1-3,
wherein R 5 and R 6 are each independently selected from the group consisting of a hydrogen, an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted arylalkyl, and an optionally substituted aryl.
2. The gold(I) complex of formula (I) of claim 1 , wherein R 1 and R 2 are each independently an optionally substituted phenyl.
3. The gold(I) complex of formula (I) of claim 1 , wherein R 1 and R 2 are each phenyl.
4. The gold(I) complex of formula (I) of claim 1 , wherein R 3 is —NH 2 .
5. The gold(I) complex of formula (I) of claim 1 , wherein n is 1.
6. The gold(I) complex of formula (I) of claim 1 , wherein R 4 is chloro.
7. The gold(I) complex of formula (I) of claim 1 , wherein R 4 is
and wherein R 5 and R 6 are each independently a C 1 to C 8 alkyl or a C 7 to C 12 arylalkyl.
8. The gold(I) complex of formula (I) of claim 7 , wherein R 5 and R 6 are each methyl, ethyl, or benzyl.
9. The gold(I) complex of formula (I) of claim 1 , which is selected from the group consisting of:
10. The gold(I) complex of formula (I) of claim 1 , which is selected from the group consisting of:
11. A pharmaceutical composition, comprising:
the gold(I) complex of formula (I) of claim 1 ; and
a pharmaceutically acceptable carrier and/or excipient.
12. The pharmaceutical composition of claim 11 , which comprises 0.5-50 μM of the gold(I) complex of formula (I) relative to a total volume of the pharmaceutical composition.
13. The pharmaceutical composition of claim 11 , wherein the pharmaceutically acceptable carrier and/or excipient is at least one selected from the group consisting of a buffer, an inorganic salt, a fatty acid, a vegetable oil, a synthetic fatty ester, a surfactant, and a polymer.
14. The pharmaceutical composition of claim 11 , wherein the gold(I) complex of formula (I) is selected from the group consisting of:
15. A method for treating a proliferative disorder, the method comprising:
administering the pharmaceutical composition of claim 11 to a subject in need of therapy.
16. The method of claim 15 , wherein 0.01-50 mg/kg of the gold(I) complex of formula (I) is administered per body weight of the subject.
17. The method of claim 15 , wherein the proliferative disorder is cancer.
18. The method of claim 17 , wherein the cancer is at least one selected from the group consisting of lung cancer, cervical cancer, and liver cancer.
19. The method of claim 17 , wherein the cancer is resistant to at least one platinum-based chemotherapy drug.
20. The method of claim 19 , wherein the platinum-based chemotherapy drug is cisplatin.