How to modify 7-azaindole to form cytotoxic Pt(II) complexes: Highly in vitro anticancer effective cisplatin derivatives involving halogeno-substituted 7-azaindole

Published: JOURNAL OF INORGANIC BIOCHEMISTRY 115, 57-63 Authors: Starha, P., Travnicek, Z., Popa, A., Popa, I., Muchova, T., Brabec, V. Year: 2012


The platinum(II) dichlorido and oxalato complexes of the general formula cis-[PtCl2(nHaza)(2)] (1-3) [Pt(ox)(nHaza)(2)] (4-6) involving 7-azaindole halogeno-derivatives (nHaza) were prepared and thoroughly characterized. A single-crystal X-ray analysis of cis-[PtCl2(3C/Haza)(2)]center dot DMF (1 center dot DMF: 3C/Haza symbolizes 3-chloro-7-azaindole) revealed a distorted square-planar arrangement with both the 3C/Haza molecules coordinated through their N7 atoms in a cis fashion. In vitro cytotoxicity of the complexes was evaluated by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay against the HOS (osteosarcoma), MCF7 (breast adenocarcinoma) and LNCaP (prostate adenocarcinoma) human cancer cell lines. The dichlorido complexes 1-3 (IC50 = 3.8, 3.9, and 2.5 mu M, respectively) showed significantly higher in vitro anticancer effect against HOS as compared with cisplatin, whose IC50 = 37.7 mu M. The biological effect of cisplatin against MCF7 (IC50 = 24.5 mu M) and LNCaP (IC50 = 3.8 mu M) was also exceeded by 1-3 (except for 2 against LNCaP), but the difference can be classified as significant only in the case of 1 (IC50 = 3.4 mu M) and 3 (IC50 = 2.0 mu M) against MCF7. The molecular pharmacological studies (RNA synthesis by T7 RNA polymerase in vitro) proved that 1-3 bind to DNA in a similar manner as cisplatin, since the RNA synthesis products of 1-3 and cisplatin showed a similar sequence profile of major bands. (C) 2012 Elsevier Inc. All rights reserved.