Synthesis, Structural
Characterization, Solution Behavior,
and in Vitro Antiproliferative Properties of a Series of Gold Complexes
with 2-(2′-Pyridyl)benzimidazole as Ligand: Comparisons of
Gold(III) versus Gold(I) and Mononuclear versus Binuclear Derivatives
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Abstract
A variety of gold(III) and gold(I) derivatives of 2-(2′-pyridyl)benzimidazole
(pbiH) were synthesized and fully characterized and their antiproliferative
properties evaluated in a representative ovarian cancer cell line.
The complexes include the mononuclear species [(pbi)AuX<sub>2</sub>] (X = Cl, <b>1</b>; OAc, <b>2</b>), [(pbiH)AuCl] (<b>3</b>), [(pbiH)Au(PPh<sub>3</sub>)][PF<sub>6</sub>] (<b>4</b>-PF<sub>6</sub>), and [(pbi)Au(L)] (L = PPh<sub>3</sub>, <b>5</b>; TPA, <b>6</b>), and the binuclear gold(I)/gold(I) and gold(I)/gold(III)
derivatives [(PPh<sub>3</sub>)<sub>2</sub>Au<sub>2</sub>(μ<sub>2</sub>-pbi)][PF<sub>6</sub>] (<b>10</b>-PF<sub>6</sub>), [ClAu(μ<sub>3</sub>-pbi)AuCl<sub>2</sub>] (<b>7</b>), and [(PPh<sub>3</sub>)Au(μ<sub>3</sub>-pbi)AuX<sub>2</sub>][PF<sub>6</sub>] (X =
Cl, <b>8</b>-PF<sub>6</sub>; OAc, <b>9</b>-PF<sub>6</sub>). The molecular structures of <b>6</b>, <b>7</b>, and <b>10</b>-PF<sub>6</sub> were determined by X-ray diffraction analysis.
The chemical behavior of these compounds in solution was analyzed
both by cyclic voltammetry in DMF and absorption UV–vis spectroscopy
in an aqueous buffer. Overall, the stability of these gold compounds
was found to be acceptable for the cellular studies. For all complexes,
relevant antiproliferative activities in vitro were documented against
A2780 human ovarian carcinoma cells, either resistant or sensitive
to cisplatin, with IC<sub>50</sub> values falling in the low micromolar
or even in the nanomolar range. The investigated gold compounds were
found to overcome resistance to cisplatin to a large degree. Results
are interpreted and discussed in the frame of current knowledge on
cytotoxic and antitumor gold compounds
