Mononuclear gold(iii) complexes with l-histidine-containing dipeptides: tuning the structural and biological properties by variation of the N-terminal amino acid and counter anion.
Gold(iii) complexes with different l-histidine-containing dipeptides, [Au(Gly-l-His-NA,NP,N3)Cl]Cl·3H2O (1a), [Au(Gly-l-His-NA,NP,N3)Cl]NO3·1.25H2O (1b), [Au(l-Ala-l-His-NA,NP,N3)Cl][AuCl4]·H2O (2a), [Au(l-Ala-l-His-NA,NP,N3)Cl]NO3·2.5H2O (2b), [Au(l-Val-l-His-NA,NP,N3)Cl]Cl·2H2O (3), [Au(l-Leu-l-His-NA,NP,N3)Cl]Cl (4a) and [Au(l-Leu-l-His-NA,NP,N3)Cl][AuCl4]·H2O (4b), have been synthesized and structurally characterized by spectroscopic (1H NMR, IR and UV-vis) and single-crystal X-ray diffraction techniques. The antimicrobial efficiency of these gold(iii) complexes, along with K[AuCl4] and the corresponding dipeptides, was evaluated against the broad panel of Gram-positive and Gram-negative bacteria and fungi, displaying their moderate inhibiting activity. Moreover, the cytotoxic properties of the investigated complexes were assessed against the normal human lung fibroblast cell line (MRC5) and two human cancer, cervix (HeLa) and lung (A549) cell lines. None of the complexes exerted significant cytotoxic activity; nevertheless complexes that did show selectivity in terms of cancer vs. normal cell lines (2a/b and 4a/b) have been evaluated using zebrafish (Danio rerio) embryos for toxicity and antiangiogenic potential. Although the gold(iii) complexes achieved an antiangiogenic effect comparable to the known angiogenic inhibitors auranofin and sunitinib malate at 30-fold higher concentrations, they had no cardiovascular side effects, which commonly accompany auranofin and sunitinib malate treatment. Finally, binding of the gold(iii) complexes to the active sites of both human and bacterial (Escherichia coli) thioredoxin reductases (TrxRs) was demonstrated by conducting a molecular docking study, suggesting that the mechanism of biological action of these complexes can be associated with their interaction with the TrxR active site.
Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89B, 61-614 Poznań, Poland. urszular@amu.edu.pl.
Beata
B
Warżajtis
Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, 34000 Kragujevac, Serbia. djuran@kg.ac.rs.
Biljana Đ
BĐ
Glišić
Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, 34000 Kragujevac, Serbia. djuran@kg.ac.rs.
Nada D
ND
Savić
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia. jasmina.nikodinovic@gmail.com.
Aleksandar
A
Pavic
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia. jasmina.nikodinovic@gmail.com.
Sandra
S
Vojnovic
Faculty of Medicine, Department of Chemistry, University of Niš, 18000 Niš, Serbia.
Aleksandar
A
Veselinović
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia. jasmina.nikodinovic@gmail.com.
Jasmina
J
Nikodinovic-Runic
Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89B, 61-614 Poznań, Poland. urszular@amu.edu.pl.
Urszula
U
Rychlewska
Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, 34000 Kragujevac, Serbia. djuran@kg.ac.rs.
Miloš I
http://orcid.org/0000-0003-2763-2852
MI
Djuran
D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D020134:Catalytic Domain; D004151:Dipeptides / Q000737:chemistry*; D004926:Escherichia coli / Q000201:enzymology; D006046:Gold / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000378:metabolism
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D004151:Dipeptides; D009942:Organometallic Compounds; D006639:Histidine; D006046:Gold; D013880:Thioredoxin-Disulfide Reductase