Synthesis, Characterization and in Vitro Antitumor Activity of Platinum(II) Oxalato Complexes Involving 7-Azaindole Derivatives as Coligands

Abstract

The platinum(II) oxalato complexes [Pt(ox)(naza)2] (1–3) were synthesized and characterized by elemental analysis (C, H, N), multinuclear NMR spectroscopy (1H, 13C, 15N, 195Pt) and electrospray ionization mass spectrometry (ESI-MS); naza = 4-chloro-7-azaindole (4Claza; 1), 3-bromo-7-azaindole (3Braza; 2) or 4-bromo-7-azaindole (4Braza; 3). The prepared substances were screened for their in vitro antitumor activity on the osteosarcoma (HOS) and breast adenocarcinoma (MCF7) human cancer cell lines, where 2 showed moderate antitumor effect (IC50 = 27.5 μM, and 18.3 μM, respectively). The complex 2 was further tested on a panel of six others human cancer cell lines, including the malignant melanoma (G361), cervix carcinoma (HeLa), ovarian carcinoma (A2780), cisplatin-resistant ovarian carcinoma (A2780R), lung carcinoma (A549) and prostate adenocarcinoma (LNCaP). This substance was found to be moderate antitumor effective against G361 (IC50 = 17.3 μM), HeLa (IC50 = 31.8 μM) and A2780 (IC50 = 19.2 μM) cell lines. The complex 2 was also studied by NMR for its solution stability and by ESI-MS experiments for its ability to interact with biomolecules, such as cysteine, glutathione or guanosine 5'-monophosphate.

Keywords

• platinum(II) complexes
• oxalato complexes
• 7-azaindole derivatives
• multinuclear NMR
• antitumor activity