title: In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-Azaindoles.
abstract: 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). TheN1-deprotonated anions of 7-azaindole or its derivatives (naza) are coordinated to the metal centre through theN1 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 complexes1-8was studied against both thecisplatin-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 complexes4,5, and8, 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) thancisplatin(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 complexes1and5, which is indicative of a different mechanism of action fromcisplatin(induced S-cell cycle phase arrest). The stability of the representative complex8in 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 and31P-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 theN-donor azaindole-based ligand in the presence of the used biomolecules.
authors.affiliation: Department of Inorganic Chemistry, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic. pavel.starha@upol.cz.
authors.forename: Pavel
authors.initials: P
authors.lastname: Štarha
authors.affiliation: Department of Inorganic Chemistry, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic. zdenek.travnicek@upol.cz.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Trávníček
authors.affiliation: Department of Inorganic Chemistry, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic. bohuslav.drahos@upol.cz.
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Drahoš
authors.affiliation: Department of Cell Biology and Genetics, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University Olomouc, Šlechtitelů 27, 783 71 Olomouc, Czech Republic. zdenek.dvorak@upol.cz.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Dvořák
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006046:Gold / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010720:Phosphines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D014867:Water / Q000737:chemistry
chemical_list: C023422:7-azaindole dimer; D000970:Antineoplastic Agents; D007211:Indoles; D010720:Phosphines; D014867:Water; D006046:Gold
keywords: 7-azaindole; antitumor activity; crystal structures; gold(I) complexes; in vitro; triphenylphosphane