In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-Azaindoles

A series of gold(I) complexes of the general composition [Au(naza)(PPh(3))] (1–8) was prepared and thoroughly characterized (e.g., electrospray ionization (ESI) mass spectrometry and multinuclear nuclear magnetic resonance (NMR) spectroscopy). The N1-deprotonated anions of 7-azaindole or its derivatives (naza) are coordinated to the metal centre through the N1 atom of their pyrrole ring, as proved by a single crystal X-ray analysis of the complexes [Au(3I5Braza)(PPh(3))] (7) and [Au(2Me4Claza)(PPh(3))]·½H(2)O (8′). The in vitro cytotoxicity of the complexes 1–8 was studied against both the cisplatin-sensitive and -resistant variants of the A2780 human ovarian carcinoma cell line, as well as against the MRC-5 human normal fibroblast cell line. The complexes 4, 5, and 8, containing deprotonated 3-iodo-7-azaindole, 5-bromo-7-azaindole, and 2-methyl-4-chloro-7-azaindole (2Me4Claza), respectively, showed significantly higher potency (IC(50) = 2.8–3.5 µM) than cisplatin (IC(50) = 20.3 µM) against the A2780 cells and markedly lower effect towards the MRC-5 non-cancerous cells (IC(50) = 26.0–29.2 µM), as compared with the mentioned A2780 cancer cells. The results of the flow cytometric studies of the A2780 cell cycle perturbations revealed a G(2)-cell cycle phase arrest of the cells treated by the representative complexes 1 and 5, which is indicative of a different mechanism of action from cisplatin (induced S-cell cycle phase arrest). The stability of the representative complex 8 in the water-containing solution as well as its ability to interact with the reduced glutathione, cysteine and bovine serum albumin was also studied using (1)H and (31)P-NMR spectroscopy (studied in the 50% DMF-d(7)/50% D(2)O mixture) and ESI+ mass spectrometry (studied in the 50% DMF/50% H(2)O mixture); DMF = dimethylformamide. The obtained results are indicative for the release of the N-donor azaindole-based ligand in the presence of the used biomolecules.