TY - JOUR
T1 - Phosphinogold(I) dithiocarbamate complexes
T2 - Effect of the nature of phosphine ligand on anticancer properties
AU - Keter, Frankline K.
AU - Guzei, Ilia A.
AU - Nell, Margo
AU - Zyl, Werner E.Van
AU - Darkwa, James
PY - 2014/2/17
Y1 - 2014/2/17
N2 - The reactions of potassium salts of the dithiocarbamates L {where L = pyrazolyldithiocarbamate (L1), 3,5-dimethylpyrazolyldithiocarbamate (L2), or indazolyldithiocarbamate (L3)} with the gold precursors [AuCl(PPh3)], [Au2Cl2(dppe)], [Au2Cl2(dppp)], or [Au2Cl2(dpph)] lead to the new gold(I) complexes [AuL(PPh3)] (1-3), [Au2L2(dppe)] (4-6), [(Au2L2)(dppp)] (7-9), and [Au2(L) 2(dpph)] (10-12) {where dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, and dpph = 1,6-bis(diphenylphosphino) hexane}. These gold compounds were characterized by a combination of NMR and infrared spectroscopy, microanalysis, and mass spectrometry; and in selected cases by single-crystal X-ray crystallography. Compounds 4-6, which have dppe ligands, are unstable in solution for prolonged periods, with 4 readily transforming to the Au18 cluster [Au18S 8(dppe)6]Cl2 (4a) in dichloromethane. Compounds 1-3 and 7-12 are all active against human cervical epithelioid carcinoma (HeLa) cells, but the most active compounds are 10 and 11, with IC50 values of 0.51 μM and 0.14 μM, respectively. Compounds 10 and 11 are more selective toward HeLa cells than they are toward normal cells, with selectivities of 25.0 and 70.5, respectively. Further tests, utilizing the 60-cell-line Developmental Therapeutics Program at the National Cancer Institute (U.S.A.), showed 10 and 11 to be active against nine other types of cancers.
AB - The reactions of potassium salts of the dithiocarbamates L {where L = pyrazolyldithiocarbamate (L1), 3,5-dimethylpyrazolyldithiocarbamate (L2), or indazolyldithiocarbamate (L3)} with the gold precursors [AuCl(PPh3)], [Au2Cl2(dppe)], [Au2Cl2(dppp)], or [Au2Cl2(dpph)] lead to the new gold(I) complexes [AuL(PPh3)] (1-3), [Au2L2(dppe)] (4-6), [(Au2L2)(dppp)] (7-9), and [Au2(L) 2(dpph)] (10-12) {where dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, and dpph = 1,6-bis(diphenylphosphino) hexane}. These gold compounds were characterized by a combination of NMR and infrared spectroscopy, microanalysis, and mass spectrometry; and in selected cases by single-crystal X-ray crystallography. Compounds 4-6, which have dppe ligands, are unstable in solution for prolonged periods, with 4 readily transforming to the Au18 cluster [Au18S 8(dppe)6]Cl2 (4a) in dichloromethane. Compounds 1-3 and 7-12 are all active against human cervical epithelioid carcinoma (HeLa) cells, but the most active compounds are 10 and 11, with IC50 values of 0.51 μM and 0.14 μM, respectively. Compounds 10 and 11 are more selective toward HeLa cells than they are toward normal cells, with selectivities of 25.0 and 70.5, respectively. Further tests, utilizing the 60-cell-line Developmental Therapeutics Program at the National Cancer Institute (U.S.A.), showed 10 and 11 to be active against nine other types of cancers.
UR - http://www.scopus.com/inward/record.url?scp=84894359294&partnerID=8YFLogxK
U2 - 10.1021/ic4025926
DO - 10.1021/ic4025926
M3 - Article
C2 - 24476103
AN - SCOPUS:84894359294
SN - 0020-1669
VL - 53
SP - 2058
EP - 2067
JO - Inorganic Chemistry
JF - Inorganic Chemistry
IS - 4
ER -
