Two copper(II) complexes containing diplacone (H4dipl), a naturally occurring C-geranylated flavanone derivative, in combination with bathophenanthroline (bphen) or 1,10-phenanthroline (phen) with the composition [Cu3(bphen)3(Hdipl)2]⋅2H2O (1) and {[Cu(phen)(H2dipl)2]⋅1.25H2O}n (2) were prepared and characterized. As compared to diplacone, the complexes enhanced in vitro cytotoxicity against A2780 and A2780R human ovarian cancer cells (IC50 ≈ 0.4-1.2 μM), human lung carcinoma (A549, with IC50 ≈ 2 μM) and osteosarcoma (HOS, with IC50 ≈ 3 μM). Cellular effects of the complexes in A2780 cells were studied using flow cytometry, covering studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/superoxide production. These results uncovered a possible mechanism of action characterized by the G2/M cell cycle arrest. The studies on human endothelial cells revealed that complexes 1 and 2, as well as their parental compound diplacone, do possess anti-inflammatory activity in terms of NF-κB inhibition. As for the effects on PPARα and/or PPARγ, complex 2 reduced the expression of leukocyte adhesion molecules VCAM-1 and E-selectin suggesting its dual anti-inflammatory capacity. A wide variety of Cu-containing coordination species and free diplacone ligand were proved by mass spectrometry studies in water-containing media, which might be responsible for multimodal effect of the complexes.
- Klíčová slova
- Anti-cancer, Cellular effects, Copper(II), Diplacone, In vitro cytotoxicity, Inflammation,
- MeSH
- antiflogistika farmakologie chemie MeSH
- antitumorózní látky * farmakologie chemie chemická syntéza MeSH
- autofagie účinky léků MeSH
- flavanony * farmakologie chemie MeSH
- komplexní sloučeniny * farmakologie chemická syntéza chemie MeSH
- lidé MeSH
- měď * chemie farmakologie MeSH
- nádorové buněčné linie MeSH
- proliferace buněk * účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiflogistika MeSH
- antitumorózní látky * MeSH
- flavanony * MeSH
- komplexní sloučeniny * MeSH
- měď * MeSH
- reaktivní formy kyslíku MeSH
Six organotin(IV) complexes, viz., [Me2Sn(L)] (1), [n-Bu2Sn(L)] (2), [n-Oct2Sn(L)] (3), [Bz2Sn(L)]·0.5C7H8 (4), [n-BuSn(L)Cl] (5), and [PhSn(L)Cl] (6), were synthesized using a 2,6-diacetylpyridine bis(2-hydroxybenzoylhydrazone), H2L. Compounds were characterized by Fourier transform infrared (FT-IR), High-resolution mass spectrometry (HRMS), and solutions Fourier transform nuclear magnetic resonance (FT-NMR) spectroscopies. The structures 1-6 were established by single-crystal X-ray diffraction (SC-XRD) analysis. Diffraction results evidenced that complexes 1-6 were seven-coordinated mononuclear species with the equatorial plane comprising the pentagonal N3O2 chelate ring of the doubly deprotonated L and two axial ligands, either R (R = Me, n-Bu, n-Oct, Bz) or R (n-Bu or Ph) and Cl ligands. Additionally, the photophysical properties were examined due to the enhanced conjugation and rigidity of the molecules while thermogravimetric analysis was carried out to evaluate the thermal stabilities of compounds. The anti-proliferative activity of the complexes 1-6 was tested against prostate cancer cells (DU-145) and normal human embryonic kidney cells (HEK-293). Among the compounds, dibutyltin compound 2 exhibited increased anti-proliferative activity, with an IC50 value of 6.16 ± 1.56 μM. The investigation of its mechanism of action involves using AO/EB (acridine orange/ethidium bromide) and ROS (reactive oxygen species) generation assays. This likely detects apoptotic morphological alterations in the nucleus of the cells, with ROS generation ultimately leading to apoptosis and cell death. The superior activity of 2 may be attributed to the C···H contacts and respective higher de outside and di inside distances from the Hirshfeld surface. Thus, these compounds could be a promising alternative to classical chemotherapy agents.
- Klíčová slova
- Crystal structure, Cytotoxicity, Heptacoordinate complexes, N(3)O(2)-pentadentate ligand, Organotin, Spectroscopy,
- Publikační typ
- časopisecké články MeSH
A bis(chalcone) molecule (H2L) was synthesized via Aldol's condensation from terephthalaldehyde and 2'-hydroxyacetophenone and it was used as bridging ligand for the preparation of five dinuclear copper(II) complexes of the composition [Cu(NN)(μ-L)Cu(NN)](NO3)2⋅nH2O (n = 0-2) (1-5), where NN stands for a bidentate N-donor ligand such as phen (1,10-phenanthroline, 1), bpy (2,2'-bipyridine, 2), mebpy (5,5'-dimethyl-2,2'-dipyridine, 3), bphen (bathophenanthroline, 4) and nphen (5-nitro-1,10-phenanthroline, 5). The compounds were characterized by different suitable techniques to confirm their purity, composition, and structure. Moreover, the products were evaluated for their in vitro cytotoxicity on a panel of human cancer cell lines: ovarian (A2780), ovarian resistant to cisplatin (A2780R), prostate (PC3), osteosarcoma (HOS), breast (MCF7) and lung (A549), and normal fibroblasts (MRC-5), showing significant cytotoxicity in most cases, with IC50 ≈ 0.35-7.8 μM. Additionally, the time-dependent cytotoxicity and cellular uptake of copper, together with flow cytometric studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/superoxide production in A2780 cells, were also performed. The results of biological testing on A2780 cells pointed out a possible mechanism of action characterized by the G2/M cell cycle arrest and induction of apoptosis by triggering the intrinsic signalling pathway associated with the damage of mitochondrial structure and depletion of mitochondrial membrane potential. SYNOPSIS: Dinuclear Cu(II) complexes bearing a bridging bis(chalcone) ligand revealed high in vitro cytotoxicity, initiated A2780 cell arrest at G2/M phase and efficiently triggered intrinsic pathway of apoptosis.
- Klíčová slova
- Bis(chalcone), Cancer, Cell cycle, Copper(II), Dinuclear complexes, In vitro cytotoxicity,
- MeSH
- antitumorózní látky * farmakologie chemie MeSH
- apoptóza MeSH
- chalkon * farmakologie MeSH
- chalkonoidy * farmakologie MeSH
- komplexní sloučeniny * farmakologie chemie MeSH
- lidé MeSH
- ligandy MeSH
- měď chemie MeSH
- nádorové buněčné linie MeSH
- nádory vaječníků * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antitumorózní látky * MeSH
- chalkon * MeSH
- chalkonoidy * MeSH
- komplexní sloučeniny * MeSH
- ligandy MeSH
- měď MeSH
Anionic cyclopentadienyl (Cp) and its pentamethyl-substituted derivative (Cp*) serve as crucial ligands for creating stable π-coordinated materials, including catalysts. From a structural perspective, the π-extended analog of Cp, known as an N-fused porphyrin (NFP), is recognized as an intriguing 18π aromatic chromophore, offering near-infrared (NIR) optical properties that can be fine-tuned through metal complexation. When coordinated with rhodium at the central NFP core, it forms a sandwich binuclear rhodium(III) complex along with terminal and bridging chloride ligands, denoted as Rh-1, and its bromo derivative, Rh-1-Br. In contrast to the bis-NFP complex of iron(II) reported previously by our team, both Rh-1 and Rh-1-Br complexes exhibit strong NIR optical properties and narrow HOMO-LUMO energy gaps, attributed to minimal orbital interactions between the two co-facial NFP ligands. Leveraging these NIR absorption properties, we assessed the photothermal conversion properties of Rh-1 and ligand 1, revealing high conversion efficiency. This suggests their potential application as photothermal agents for use in photothermal therapy.
- Klíčová slova
- N-fused porphyrin, NIR absorption, Photothermal conversion, Rhodium, Sandwich metal complex,
- MeSH
- chloridy MeSH
- katalýza MeSH
- ligandy MeSH
- porfyriny * chemie MeSH
- rhodium * chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chloridy MeSH
- ligandy MeSH
- porfyriny * MeSH
- rhodium * MeSH
Two silver(I) complexes with biologically relevant heterocyclic ligands, pyrrole and furan-2- carboxylic acid, were synthesized and their composition was confirmed using elemental, spectral, thermal and structural analyses. The {[Ag(Py2c)]}n (AgPy2c, Py2c = pyrrole-2-carboxylate) and {[Ag(Fu2c)]}n (AgFu2c, Fu2c = furan-2-carboxylate) solubility and stability in biological test stock solution were confirmed by 1H NMR spectroscopy. The X-ray analysis has enabled us to determine typical argentophilic interactions and bridging carboxylate coordination mode of both ligands. Potentiometric data analysis by BSTAC program resulted in the determination of the stability constant of only one species, i.e., the ML (M = Ag+, L = Fu2c-), log βML = 0.59 ± 0.04. Antimicrobial and anticancer tests were performed against selected microorganisms and cell lines with new silver(I) complexes and compared with AgSD (silver(I) sulfadiazine) and cisplatin. From their microbial toxicity point of view, selectivity was determined against lactobacilli (AgPy2c is 8× more effective against S. aureus and E. coli and AgFu2c is 8× more effective against E. coli and 4× against S. aureus). AgFu2c significant anticancer activity was determined against Jurkat cell lines (IC50 = 8.00 μM) and was similar to cisPt (IC50 = 6.3 μM) similarly to its selectivity (SI (AgFu2c) = 7.3, SI (cisPt) = 6.4, SI = selectivity index). In addition, cell cycle arrest was observed already in the Sub-G0 phase during a flow cytometry experiment. To evaluate the AgPy2c and AgFu2c bioavailability we also discuss their Lipinski's Rule of Five.
- Klíčová slova
- Anticancer, Antimicrobial, Cell cycle, Crystallography, Lipophilicity, Potentiometry, Selectivity, Silver(I) complexes, Stability,
- MeSH
- antibakteriální látky farmakologie chemie MeSH
- antiinfekční látky * farmakologie chemie MeSH
- Escherichia coli MeSH
- furany farmakologie MeSH
- komplexní sloučeniny * farmakologie chemie MeSH
- ligandy MeSH
- mikrobiální testy citlivosti MeSH
- Staphylococcus aureus MeSH
- stříbro farmakologie chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 2-furoic acid MeSH Prohlížeč
- antibakteriální látky MeSH
- antiinfekční látky * MeSH
- furany MeSH
- komplexní sloučeniny * MeSH
- ligandy MeSH
- stříbro MeSH
A new heteroleptic copper(II) compound named C0-UDCA was prepared by reaction of [Cu(phen)2(OH2)](ClO4)2 (C0) with the bile ursodeoxycholic acid (UDCA). The resulting compound is able to inhibit the lipoxygenase enzyme showing more efficacy than the precursors C0 and UDCA. Molecular docking simulations clarified the interactions with the enzyme as due to allosteric modulation. The new complex shows antitumoral effect on ovarian (SKOV-3) and pancreatic (PANC-1) cancer cells at the Endoplasmic Reticulum (ER) level by activating the Unfolded Protein Response. In particular, the chaperone BiP, the pro-apoptotic protein CHOP and the transcription factor ATF6 are upregulated in the presence of C0-UDCA. The combination of Intact Cell MALDI-MS and statistical analysis have allowed us to discriminate between untreated and treated cells based on their mass spectrometry fingerprints.
- Klíčová slova
- Copper complex, ER stress, Lipoxygenase, Mass spectrometry, Molecular docking, Solution equilibria,
- MeSH
- apoptóza MeSH
- buněčné linie MeSH
- fenantroliny chemie MeSH
- inhibitory enzymů farmakologie MeSH
- inhibitory lipoxygenas * farmakologie MeSH
- kyselina ursodeoxycholová farmakologie MeSH
- měď farmakologie chemie MeSH
- nádory slinivky břišní MeSH
- nádory * MeSH
- simulace molekulového dockingu MeSH
- stres endoplazmatického retikula MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fenantroliny MeSH
- inhibitory enzymů MeSH
- inhibitory lipoxygenas * MeSH
- kyselina ursodeoxycholová MeSH
- měď MeSH
The antioxidant properties of flavonoids are mediated by their functional hydroxyl groups, which are capable of both chelating redox active metals such as iron, copper and scavenging free radicals. In this paper, the antioxidant vs. prooxidant and DNA protecting properties of baicalein and Cu(II)-baicalein complexes were studied under the conditions of the Copper-Fenton reaction and of the Copper-Ascorbate system. From the relevant EPR spectra, the interaction of baicalein with Cu(II) ions was confirmed, while UV-vis spectroscopy demonstrated a greater stability over time of Cu(II)-baicalein complexes in DMSO than in methanol and PBS and Phosphate buffers. An ABTS study confirmed a moderate ROS scavenging efficiency, at around 37%, for both free baicalein and Cu(II)-baicalein complexes (in the ratios 1:1 and 1:2). The results from absorption titrations are in agreement with those from viscometric studies and confirmed that the binding mode between DNA and both free baicalein and Cu-baicalein complexes, involves hydrogen bonds and van der Waals interactions. The DNA protective effect of baicalein has been investigated by means of gel electrophoresis under the conditions of the Cu-catalyzed Fenton reaction and of the Cu-Ascorbate system. In both cases, it was found that, at sufficiently high concentrations, baicalein offers some protection to cells from DNA damage caused by ROS (singlet oxygen, hydroxyl radicals and superoxide radical anions). Accordingly, baicalein may be useful as a therapeutic agent in diseases with a disturbed metabolism of redox metals such as copper, for example Alzheimer's disease, Wilson's disease and various cancers. While therapeutically sufficient concentrations of baicalein may protect neuronal cells from Cu-Fenton-induced DNA damage in regard to neurological conditions, conversely, in the case of cancers, low concentrations of baicalein do not inhibit the pro-oxidant effect of copper ions and ascorbate, which can, in turn, deliver an effective damage to DNA in tumour cells.
- Klíčová slova
- Antioxidant, Baicalein, Copper(II), DNA damage, Gel electrophoresis, Prooxidant, Radical scavenging, Spectroscopy,
- MeSH
- antioxidancia * chemie MeSH
- DNA metabolismus MeSH
- flavonoidy MeSH
- hydroxylový radikál metabolismus MeSH
- kovy MeSH
- kyselina askorbová MeSH
- měď * chemie MeSH
- oxidace-redukce MeSH
- poškození DNA MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antioxidancia * MeSH
- baicalein MeSH Prohlížeč
- DNA MeSH
- flavonoidy MeSH
- hydroxylový radikál MeSH
- kovy MeSH
- kyselina askorbová MeSH
- měď * MeSH
- reaktivní formy kyslíku MeSH
The tumour suppressor p53 regulates the expression of a myriad of proteins that are important for numerous cellular processes, including apoptosis, cell cycle arrest, DNA repair, metabolism, and even autophagy and ferroptosis. Aside from DNA, p53 can interact with many types of partners including proteins and small organic molecules. The ability of p53 to interact with heme has been reported so far. In this study, we used various spectroscopic studies to conduct a thorough biophysical characterization of the interaction between p53 and heme concerning the oxidation, spin, coordination, and ligand state of heme iron. We found that the p53 oligomeric state and zinc biding ability are preserved upon the interaction with heme. Moreover, we described the effect of heme binding on the conformational dynamics of p53 by hydrogen/deuterium exchange coupled with mass spectrometry. Specifically, the conformational flexibility of p53 is significantly increased upon interaction with heme, while its affinity to a specific DNA sequence is reduced by heme. The inhibitory effect of DNA binding by heme is partially reversible. We discuss the potential heme binding sites in p53 with respect to the observed conformational dynamics changes and perturbed DNA-binding ability of p53 upon interaction with heme.
- Klíčová slova
- Conformational dynamics, Heme interaction, Heme-responsive sensor, Intrinsically disordered regions, Signal transduction, p53 transcription factor,
- MeSH
- deuterium metabolismus MeSH
- DNA MeSH
- hem chemie MeSH
- hmotnostní spektrometrie metody MeSH
- konformace proteinů MeSH
- lidé MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- nádory * MeSH
- vodík * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- deuterium MeSH
- DNA MeSH
- hem MeSH
- nádorový supresorový protein p53 MeSH
- vodík * MeSH
A series of five decavanadates (V10) using a simple, one-pot synthesis, adhering to the model template: transition metal ion - decavanadate - ligands:(Hnicotinamide)2{[Co(H2O)3(nicotinamide)2]2[μ-V10O28]}.6H2O (1), {[Co(H2O)4(isonicotinamide)2]3}V10O28·4H2O (2), {[Co(H2O)4]2[Co(H2O)2(μ-pyrazinamide)2][μ-V10O28]}·4H2O (3) {[Co(H2O)4(μ-pyrazinamide)]3.V10O28}·4H2O (4), and (NH4)2{[Ni(H2O)4(2-hydroxyethylpyridine)]2}V10O28·2H2O (5) was synthesized. X-ray analysis reveals that 1 and 3 are decavanadato complexes, while 2, 4 and 5 are decavanadate complex salts. Moreover, 3 is the first example of a polymeric decavanadato complex, employing direct coordination with the metal center and the organic ligand, in toto. From the solution studies using 51V NMR spectroscopy, it was decoded that 1 and 3 stay stable in the model buffer solution and aqueous media. Binding to model proteins, cytotoxicity and water oxidation catalysis (WOC) was studied primarily for 1 and 3 and concluded that neither 1 nor 3 have an interaction with the model proteins thaumatin, lysozyme and proteinase K, because of the presence of the organic ligands in the Co(II) center, any further interplay with the proteins was blocked. Cytotoxicity studies reveal that 1 is 40% less toxic (0.05 mM) and 26% less toxic (0.1 mM) than the uncoordinated V10 with human cell lines A549 and HeLa respectively. In WOC, 1 performed superior activity, by evolving 143.37 nmol of O2 which is 700% (9-fold) increase than the uncoordinated V10.
- Klíčová slova
- Bioinorganic chemistry, Cell viability, Cytotoxicity, Decavanadate, Protein binding, Water oxidation catalysis,
- MeSH
- anionty MeSH
- katalýza MeSH
- kobalt * chemie MeSH
- lidé MeSH
- ligandy MeSH
- pyrazinamid MeSH
- vanadáty * chemie MeSH
- voda chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- anionty MeSH
- kobalt * MeSH
- ligandy MeSH
- pyrazinamid MeSH
- vanadáty * MeSH
- voda MeSH
In this work four vanadium complexes (compounds 1, 2, 3 and 4) and one molybdenum complex (compound 5) with hydrazone ligands derived from pyridoxal were synthesized and characterized. All compounds are mononuclear species, two of them (compounds 3 and 5) are dioxide complexes and the other three (compounds 1, 2 and 4) monoxide complexes. The vanadium atom of the compound 3 is five-coordinated and all the other compounds have a six coordinated environment polyhedron. The poses for the potential intercalation of the compounds 2 and 3 with DNA were obtained by using AutoDock software. Optimizations were also performed at PM6-D3H4 semi-empirical level whereas the study of the nature of the interaction was carried out by means of the Energy Decomposition Analysis and the Non-Covalent Interaction index by using in both cases Density Functional Theory computations. The cytotoxicity in lung cancer cells (A549 cell line) of all the compounds was also evaluated. After 24 h of treatment, vanadium complexes showed high values of IC50, between 419.93 ± 22.58 and 685.88 ± 46.55 μM. After 48 h, the results showed that the compound 3 had the lowest IC50 value, 65.32 ± 9.95 μM, and the compound 2 the highest value, 375.28 ± 32.09 μM. The molybdenum complex showed the lowest IC50 value at 48 h (11.22 ± 1.34 μM). The toxicity of the compounds 3, 4 and 5 was tested in vivo, using zebrafish model, and the molybdenum complex showed higher toxic effects than the studied vanadium complexes.
- Klíčová slova
- A549 cell line, Cytotoxicity, Intercalator, Stability, Vanadium, Zebrafish model,
- MeSH
- dánio pruhované MeSH
- ligandy MeSH
- molybden * chemie farmakologie MeSH
- pyridoxal farmakologie MeSH
- vanad * chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ligandy MeSH
- molybden * MeSH
- pyridoxal MeSH
- vanad * MeSH
