A comparative study on cisplatin analogs containing 7-azaindole (7AIH) and its seven halogeno-derivatives: Vibrational spectra, DFT calculations and in vitro antiproliferative activity. Crystal and molecular structure of cis-[PtCl2(4Br7AIH)2]·DMF

Abstract

Eight platinum(II) complexes of the general formula cis-[PtCl2(L)2] containing 7-azaindole (L = 7AIH) and its halogeno-derivatives: L = 3-chloro-7-azaindole (3Cl7AIH); 3-bromo-7-azaindole (3Br7AIH); 4-chloro-7-azaindole (4Cl7AIH); 4-bromo-7-azaindole (4Br7AIH); 5-bromo-7-azaindole (5Br7AIH); 3-bromo-4-chloro-7-azaindole (3Br4Cl7AIH) and 5-bromo-3-chloro-7-azaindole (5Br3Cl7AIH) were prepared. Two complexes, cis-[PtCl2(3Br4Cl7AIH)2] (2) and cis-[PtCl2(4Br7AIH)2]·DMF, are reported for the first time. Crystal structure of the latter compound has been determined with X-ray diffraction analysis (space group P43, with a = 14.775(2), c = 41.640(8) Å, V = 9090(3) Å3 and Z = 16). For all of these complexes, formation of the cis isomers in the solid state was confirmed by experimental vibrational (IR and Raman) spectroscopy combined with DFT calculations. A complete assignment of the IR and Raman spectra was made on the basis of the calculated potential energy distribution (PED). Stability of complex (2) in DMSO solution was investigated by FT-IR (ATR) spectroscopy. The in vitro antiproliferative activity of cis-[PtCl2(3Br4Cl7AIH)2], cis-[PtCl2(3Cl7AIH)2] and cis-[PtCl2(3Br7AIH)2] was evaluated on selected human cancer cell lines and towards normal mouse fibroblast cell line (BALB/3T3). All complexes are more toxic than cisplatin against Es-2 (ovarian cancer), LNCaP (prostate adenocarcinoma) and MCF7 (breast cancer). Moreover, complex (2) is significantly more active than the other complexes on A549 (lung carcinoma, IC50 = 3.9 μM). However, the three investigated Pt(II) complexes with 7-azaindoles have revealed higher cytotoxicity against a normal cell line (BALB/3T3), in comparison to cisplatin.