Synthesis, characterization and in vitro antitumor activity of platinum(II) oxalato complexes involving 7-azaindole derivatives as coligands.

Pavel Štarha,Zdeněk Dvořák,Igor Popa,Zdeněk Trávníček

doi:10.3390/molecules190810832

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.

Highlights

Platinum carboxylates represent a notable group of transition metal complexes, which have been used for the treatment of various types of cancer for many years [1,2,3]
Search for novel antitumor active platinum complexes in terms of novel carrier (i.e., N-donor ligands) and leaving ligands is one of the crucial challenge of modern bioinorganic chemistry [11,12,13], those involved in clinically used drugs are still substantial part of this research, as exemplified by the NH3 carrier ligands involved in original platinum-based drug cisplatin, as well as in currently studied picoplatin [14]
As for the biologically effective platinum oxalato complexes, it is quite interesting that these complexes can be considered, thanks to clinically used anticancer drug oxaliplatin [15], as biologically perspective group of compounds [16], not many papers dealing with such compounds in connection with their biological effect have been reported in last five years [17,18,19,20,21,22,23,24]

Summary

Introduction

Platinum carboxylates represent a notable group of transition metal complexes, which have been used for the treatment of various types of cancer for many years [1,2,3]. As for the biologically effective platinum oxalato complexes, it is quite interesting that these complexes can be considered, thanks to clinically used anticancer drug oxaliplatin [15], as biologically perspective group of compounds [16], not many papers dealing with such compounds in connection with their biological effect have been reported in last five years [17,18,19,20,21,22,23,24]. Our research group reported the platinum(II) oxalato complexes involving variously substituted N6-benzyladenine derivatives [17,18,19], whose the most effective representatives showed IC50(HOS) = 3.6 μM ([Pt(ox)(L1)]; L1=2-chloro-N6-(2-methoxybenzyl)-9-isopropyladenine) and IC50(MCF7) = 3.6 μM ([Pt(ox)(L2)]; L2=2-chloro-N6-(2,4-dimethoxybenzyl)-9-isopropyladenine)

Methods

Results

Conclusion