In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-Azaindoles
A series of gold(I) complexes of the general composition [Au(naza)(PPh3)] (1–8) was prepared and thoroughly characterized (e.g., electrospray ionization (ESI) mass spectrometry and multinuclear nuclear magnetic resonance (NMR) spectroscopy). The N1-deprotonated anions of 7-azaindole or its derivativ...
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doaj-0d2229f1efe64560a4ccb8419b2684a12020-11-24T22:22:24ZengMDPI AGInternational Journal of Molecular Sciences1422-00672016-12-011712208410.3390/ijms17122084ijms17122084In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-AzaindolesPavel Štarha0Zdeněk Trávníček1Bohuslav Drahoš2Zdeněk Dvořák3Department of Inorganic Chemistry, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech RepublicDepartment of Inorganic Chemistry, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech RepublicDepartment of Inorganic Chemistry, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech RepublicDepartment of Cell Biology and Genetics, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University Olomouc, Šlechtitelů 27, 783 71 Olomouc, Czech RepublicA series of gold(I) complexes of the general composition [Au(naza)(PPh3)] (1–8) was prepared and thoroughly characterized (e.g., electrospray ionization (ESI) mass spectrometry and multinuclear nuclear magnetic resonance (NMR) spectroscopy). The N1-deprotonated anions of 7-azaindole or its derivatives (naza) are coordinated to the metal centre through the N1 atom of their pyrrole ring, as proved by a single crystal X-ray analysis of the complexes [Au(3I5Braza)(PPh3)] (7) and [Au(2Me4Claza)(PPh3)]·½H2O (8′). The in vitrocytotoxicity of the complexes 1–8 was studied against both the cisplatin-sensitive and -resistant variants of the A2780 human ovarian carcinoma cell line, as well as against the MRC-5 human normal fibroblast cell line. The complexes 4, 5, and 8, containing deprotonated 3-iodo-7-azaindole, 5-bromo-7-azaindole, and 2-methyl-4-chloro-7-azaindole (2Me4Claza), respectively, showed significantly higher potency (IC50 = 2.8–3.5 µM) than cisplatin (IC50 = 20.3 µM) against the A2780 cells and markedly lower effect towards the MRC-5 non-cancerous cells (IC50 = 26.0–29.2 µM), as compared with the mentioned A2780 cancer cells. The results of the flow cytometric studies of the A2780 cell cycle perturbations revealed a G2-cell cycle phase arrest of the cells treated by the representative complexes 1 and 5, which is indicative of a different mechanism of action from cisplatin (induced S-cell cycle phase arrest). The stability of the representative complex 8 in the water-containing solution as well as its ability to interact with the reduced glutathione, cysteine and bovine serum albumin was also studied using 1H and 31P-NMR spectroscopy (studied in the 50% DMF-d7/50% D2O mixture) and ESI+ mass spectrometry (studied in the 50% DMF/50% H2O mixture); DMF = dimethylformamide. The obtained results are indicative for the release of the N-donor azaindole-based ligand in the presence of the used biomolecules.http://www.mdpi.com/1422-0067/17/12/2084gold(I) complexes7-azaindoletriphenylphosphanecrystal structuresantitumor activityin vitro |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pavel Štarha Zdeněk Trávníček Bohuslav Drahoš Zdeněk Dvořák |
spellingShingle |
Pavel Štarha Zdeněk Trávníček Bohuslav Drahoš Zdeněk Dvořák In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-Azaindoles International Journal of Molecular Sciences gold(I) complexes 7-azaindole triphenylphosphane crystal structures antitumor activity in vitro |
author_facet |
Pavel Štarha Zdeněk Trávníček Bohuslav Drahoš Zdeněk Dvořák |
author_sort |
Pavel Štarha |
title |
In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-Azaindoles |
title_short |
In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-Azaindoles |
title_full |
In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-Azaindoles |
title_fullStr |
In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-Azaindoles |
title_full_unstemmed |
In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-Azaindoles |
title_sort |
in vitro antitumor active gold(i) triphenylphosphane complexes containing 7-azaindoles |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2016-12-01 |
description |
A series of gold(I) complexes of the general composition [Au(naza)(PPh3)] (1–8) was prepared and thoroughly characterized (e.g., electrospray ionization (ESI) mass spectrometry and multinuclear nuclear magnetic resonance (NMR) spectroscopy). The N1-deprotonated anions of 7-azaindole or its derivatives (naza) are coordinated to the metal centre through the N1 atom of their pyrrole ring, as proved by a single crystal X-ray analysis of the complexes [Au(3I5Braza)(PPh3)] (7) and [Au(2Me4Claza)(PPh3)]·½H2O (8′). The in vitrocytotoxicity of the complexes 1–8 was studied against both the cisplatin-sensitive and -resistant variants of the A2780 human ovarian carcinoma cell line, as well as against the MRC-5 human normal fibroblast cell line. The complexes 4, 5, and 8, containing deprotonated 3-iodo-7-azaindole, 5-bromo-7-azaindole, and 2-methyl-4-chloro-7-azaindole (2Me4Claza), respectively, showed significantly higher potency (IC50 = 2.8–3.5 µM) than cisplatin (IC50 = 20.3 µM) against the A2780 cells and markedly lower effect towards the MRC-5 non-cancerous cells (IC50 = 26.0–29.2 µM), as compared with the mentioned A2780 cancer cells. The results of the flow cytometric studies of the A2780 cell cycle perturbations revealed a G2-cell cycle phase arrest of the cells treated by the representative complexes 1 and 5, which is indicative of a different mechanism of action from cisplatin (induced S-cell cycle phase arrest). The stability of the representative complex 8 in the water-containing solution as well as its ability to interact with the reduced glutathione, cysteine and bovine serum albumin was also studied using 1H and 31P-NMR spectroscopy (studied in the 50% DMF-d7/50% D2O mixture) and ESI+ mass spectrometry (studied in the 50% DMF/50% H2O mixture); DMF = dimethylformamide. The obtained results are indicative for the release of the N-donor azaindole-based ligand in the presence of the used biomolecules. |
topic |
gold(I) complexes 7-azaindole triphenylphosphane crystal structures antitumor activity in vitro |
url |
http://www.mdpi.com/1422-0067/17/12/2084 |
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