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

Abstract

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 ( 1 H, 13 C, 15 N, 195 Pt) 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 (IC 50 = 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 (IC 50 = 17.3 μM), HeLa (IC 50 = 31.8 μM) and A2780 (IC 50 = 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.

Rhodium-Catalyzed Regioselective C–H Chlorination of 7-Azaindoles Using 1,2-Dichloroethane

“…The azaindole skeleton is one of the most attractive frameworks as a bioisostere for indoles with a wide range of biological and pharmacological activities, and has been found in numerous biologically active natural products and marketed drugs . Due to their ability to act as both hydrogen-bond donor and acceptor, azaindoles have exhibited a broad spectrum of biological activities such as antitumor, antibacterial, and anti-inflammatory activity . The structural feature of electron-rich azole and electron-deficient azine rings in the 7-azaindoles makes them a unique structure in many therapeutic agents, such as marketed anticancer drug Vemurafenib, hNK1 receptor, and potent antimelanoma agent PLX4720 .…”

Anti-myeloma pro-apoptotic Pt(ii) diiodido complexes

“…17 For example, complex cis-[Pt (3Braza) 2 I 2 ] was more potent in MCF-7 breast carcinoma cell line than its dichlorido and oxalato analogues; 3Braza = 3-bromo-7-azaindole. [26][27][28] Thus, we hypothesized for this work that the known cytotoxicity of dichlorido complexes with various imidazole derivatives [23][24][25] could be improved for the new substituted-imidazole-based diiodidoplatinum(II) complexes, which could be, in contrast to cisplatin, potent against hard-to-treat human tumours (i.e. multiple myeloma in this work) as a consequence of their different MoA.…”

Synthesis, X-ray crystal structure and biological evaluation of zinc(II)-dichlorido complexes with 9-deazahypoxathine derivatives

“…90112714) and prostate adenocarcinoma (LNCaP; ECACC no. 89110211) by an MTT assay [25]. The human A2780, PC3 and LNCaP cancer cell lines were purchased from European Collection of Cell Cultures (ECACC).…”