Phosphinogold(I) dithiocarbamate complexes: effect of the nature of phosphine ligand on anticancer properties.
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 [Au18S8(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.
Department of Chemistry, University of Johannesburg , P.O. Box 524 , Auckland Park 2006, South Africa.
Frankline K
FK
Keter
Ilia A
IA
Guzei
Margo
M
Nell
Werner E van
WE
Zyl
James
J
Darkwa
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D005260:Female; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D010720:Phosphines / Q000737:chemistry*; D013859:Thiocarbamates / Q000737:chemistry*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D010720:Phosphines; D013859:Thiocarbamates; D006046:Gold; C044646:phosphine