Phosphinogold(I) Dithiocarbamate Complexes: Effect of the Nature of Phosphine Ligand on Anticancer Properties

The reactions of potassium salts of the dithiocarbamates <b>L</b> {where <b>L</b> = pyrazolyldithiocarbamate (<b>L1</b>), 3,5-dimethylpyrazolyldithiocarbamate (<b>L2</b>), or indazolyldithiocarbamate (<b>L3</b>)} with the gold precursors [AuCl­(PPh<sub>3</sub>)], [Au<sub>2</sub>Cl<sub>2</sub>­(dppe)], [Au<sub>2</sub>Cl<sub>2</sub>­(dppp)], or [Au<sub>2</sub>Cl<sub>2</sub>­(dpph)] lead to the new gold­(I) complexes [Au<b>L</b>(PPh<sub>3</sub>)] (<b>1</b>–<b>3</b>), [Au<sub>2</sub><b>L</b><sub>2</sub>­(dppe)] (<b>4</b>–<b>6</b>), [(Au<sub>2</sub><b>L</b><sub>2</sub>)­(dppp)] (<b>7</b>–<b>9</b>), and [Au<sub>2</sub>(<b>L</b>)<sub>2­</sub>(dpph)] (<b>10</b>–<b>12</b>) {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 <b>4</b>–<b>6</b>, which have dppe ligands, are unstable in solution for prolonged periods, with <b>4</b> readily transforming to the Au<sub>18</sub> cluster [Au<sub>18</sub>S<sub>8</sub>­(dppe)<sub>6</sub>]­Cl<sub>2</sub> (<b>4a</b>) in dichloromethane. Compounds <b>1</b>–<b>3</b> and <b>7</b>–<b>12</b> are all active against human cervical epithelioid carcinoma (HeLa) cells, but the most active compounds are <b>10</b> and <b>11</b>, with IC<sub>50</sub> values of 0.51 μM and 0.14 μM, respectively. Compounds <b>10</b> and <b>11</b> 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 <b>10</b> and <b>11</b> to be active against nine other types of cancers.