4-Azaindole (1H-pyrrolo[3,2-b]pyridine; 4aza) and its N1-alkylated derivative N1-isopropyl-4-azaindole (1-(propan-2-yl)-1H-pyrrolo[3,2-b]pyridine; ip4aza) have been used for the preparation of the cis-diiodido-platinum(II) complexes cis-[Pt(4aza)2I2] (1), cis-[PtI2(ip4aza)2] (2), cis-[Pt(4aza)I2(NH3)] (3) and cis-[PtI2(ip4aza)(NH3)] (4). The prepared complexes were thoroughly characterized (e.g., multinuclear NMR spectroscopy and ESI mass spectrometry) and their in vitro cytotoxicity was assessed at human ovarian carcinoma (A2780), cisplatin-resistant ovarian carcinoma (A2780R) and colon carcinoma (HT-29) cell lines, where they showed, in some cases, significantly higher activity than the used reference-drug cisplatin. The results of in vitro cytotoxicity testing at the A2780 and A2780R cells indicated that alkylation of the 4-azaindole moiety at the position of the N1 atom had a positive biological effect, because the ip4aza-containing complexes 2 and 4 showed significantly (p < 0.005) higher cytotoxicity than 4aza-containing analogues 1 and 3. The resistance factors (A2780R/A2780 model) equalled 0.8-1.4, indicating the ability of complexes 1-4 to overcome the acquired resistance of the A2780 cells against cisplatin. Complexes 1 and 2 revealed low toxicity against primary culture of human hepatocytes. The flow cytometry studies of the A2780 cell cycle modification showed that complexes 1-4 induce different cell cycle perturbations as compared with cisplatin, thus suggesting a different mechanism of their antitumor action.
Keywords: 4-Azaindole; Cytotoxicity; In vitro; Iodido; Platinum(II) complexes.