vanadium complex
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The structures of two stereoisomers of the chiral anion [VO2(N-salicylidene-isoleucinato)](-) possessing three centers of chirality, the vanadium atom (configuration A/C) and the isoleucine moiety (configuration R/S on alpha and beta carbons), are presented. The absolute configuration of all available stereosiomers, CSS, ARR, CSR and ARS, was determined by electronic circular dichroism (ECD), which allows distinguishing between diastereomers, and by vibrational circular dichroism (VCD) capable of differentiating between all four stereoisomers. The comparison of experimental VCD and infrared (IR) spectra with simulated spectra for band assignment revealed the IR spectra of the diastereomers differing significantly in the CH stretching region of the aromatic part in the molecule. Crystallization from binary systems composed of equal ratio of two stereoisomers of isoleucine, unveiled the lower solubility of CSS and ARR stereoisomers, while a longer crystallization time of the CSR and ARS stereoisomers allowed proceeding the vanadium-catalyzed epimerization, leading to the subsequent presence of the CSS and ARR stereoisomers in the product obtained.
- MeSH
- isomerie MeSH
- komplexní sloučeniny chemie MeSH
- Schiffovy báze chemie MeSH
- vanad chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This work describes cytotoxic effect of non-platinum metal-based compounds on the human T-leukemic cells with different p53 status (p53 wild-type MOLT-4 and p53-deficient Jurkat cells). The cytotoxic and apoptosis-inducing effect of the vanadium complex [(η(5)-C5H5)2V(5-NH2-phen)]OTf (V1) and molybdenum complex [(η(3)-C3H5)Mo(CO)2(phen)Cl] (Mo1) were studied using flow cytometry, spectrophotometry and Western blotting. We found that the cytotoxic effect of both tested complexes after 24 h is higher against the both examined cell lines than that of cis-platin (cis-DDP). At later investigated time intervals of 48 and 72 h, the cytotoxic effect of the cis-DDP increased but the values of the cytotoxicity of the tested V1 and Mo1 complexes remained unchanged, with the cytotoxicity of V1 comparable to that of cis-DDP. Furthermore we observed that the apoptotic process was induced by the activation of the caspases 9 (intrinsic pathway) and 8 (extrinsic pathway) in cells exposed to evaluated complexes. In case of the p53 wild-type MOLT-4 cells, the expression of the tumor-suppressor protein p53 and its form phosphorylated at the serine 15 increased after both V1 and Mo1 treatment, similar to the effect of cis-DDP.
- MeSH
- apoptóza účinky léků MeSH
- fosforylace účinky léků MeSH
- kaspasy metabolismus MeSH
- leukemie T-buněčná farmakoterapie metabolismus patologie MeSH
- lidé MeSH
- molybden chemie farmakologie MeSH
- nádorové buněčné linie MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- organokovové sloučeniny chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- serin metabolismus MeSH
- vanad chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Komplexy kovov s biologickou aktivitou predstavujú perspektívnu a rýchle sa rozvíjajúcu oblasť farmakoterapie. Po prvej časti prehľadu o metalofarmakách venovanej antimikróbnym účinkom komplexov kovov a ich využitiu v diagnostike ochorení a druhej časti zaoberajúcej sa úlohou týchto zlúčenín v liečbe rakoviny sa táto tretia a záverečná časť prehľadu zameriava na vybrané ďalšie aplikácie kovov v terapii (predovšetkým na terapiu reumatoidnej artritídy, niektorých psychických ochorení, diabetu, ako aj na chelatačnú terapiu). Popri stručnom náčrte historického vývoja klinického využitia danej kategórie liečiv sú diskutované tiež ich chemické vlastnosti, toxicita, klinické aplikácie a mechanizmus účinku. Tento stručný prehľad má za cieľ poskytnúť základnú orientáciu v tejto problematike pre farmaceutov, chemikov a ostatných záujemcov o danú oblasť z radov odbornej verejnosti, ako aj motivovať k ďalšiemu štúdiu tejto atraktívnej oblasti farmaceutického výskumu.
Bioactive metal complexes represent a promising and rapidly evolving area of pharmacotherapy. After the first part of our survey on metallopharmaceuticals dealing with antimicrobial activity of metal complexes and their application in diagnostics and the second part dedicated to anticancer properties of these compounds, this third and last part of the review focuses on several other applications of metals in therapy (mainly on the therapy of rheumatoid arthritis, some mental diseases, diabetes, as well as on chelation therapy). Following a brief account of the historical development of clinical use of the respective category of drugs, their chemical properties, toxicity, clinical applications and mechanism of action are discussed. The aim of this brief survey is to provide basic outline of the area of metallopharmacy, aimed at specialists in pharmacy and chemistry as well as at the general educated public.
- Klíčová slova
- metalofarmaka,
- MeSH
- chelátová terapie metody MeSH
- kovy * terapeutické užití MeSH
- lidé MeSH
- lithium terapeutické užití MeSH
- vanad terapeutické užití MeSH
- zlato terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Early phase diagnosis of human diseases has still been a challenge in the medicinal field, and one of the efficient non-invasive techniques that is vastly used for this purpose is magnetic resonance imaging (MRI). MRI is able to detect a wide range of diseases and conditions, including nervous system disorders and cancer, and uses the principles of NMR relaxation to generate detailed internal images of the body. For such investigation, different metal complexes have been studied as potential MRI contrast agents. With this in mind, this work aims to investigate two systems containing the vanadium complexes [VO(metf)2]·H2O (VC1) and [VO(bpy)2Cl]+ (VC2), being metformin and bipyridine ligands of the respective complexes, with the biological targets AMPK and ULK1. These biomolecules are involved in the progression of Alzheimer's disease and triple-negative breast cancer, respectively, and may act as promising spectroscopic probes for detection of these diseases. To initially evaluate the behavior of the studied ligands within the aforementioned protein active sites and aqueous environment, four classical molecular dynamics (MD) simulations including VC1 + H2O (1), VC2 + H2O (2), VC1 + AMPK + H2O (3), and VC2 + ULK1 + H2O (4) were performed. From this, it was obtained that for both systems containing VCs and water only, the theoretical calculations implied a higher efficiency when compared with DOTAREM, a famous commercially available contrast agent for MRI. This result is maintained when evaluating the system containing VC1 + AMPK + H2O. Nevertheless, for the system VC2 + ULK1 + H2O, there was observed a decrease in the vanadium complex efficiency due to the presence of a relevant steric hindrance. Despite that, due to the nature of the interaction between VC2 and ULK1, and the nature of its ligands, the study gives an insight that some modifications on VC2 structure might improve its efficiency as an MRI probe.
- Publikační typ
- časopisecké články MeSH
Ten new vanadocene complexes bearing N,N'-chelating ligands were prepared, characterized, and their cytotoxicity toward a panel of cancer cells was measured. Structures of four vanadocene compounds were determined by single crystal X-ray diffraction analysis. Complexes containing 1,2-bis(phenylimino)acenaphthene (bian) and 1,2-bis(4-methoxyphenylimino)acenaphthene (4-MeO-bian) exhibit higher cytotoxicity than those with dipyrido[3,2-a:2',3'-c]phenazine (dppz) and (E)-N-((pyridin-2-yl)methylene)benzenamine (pyma). In light of the finding, cytotoxic mechanisms of two highly effective complexes [(η5-C5H4Me)2V(bian)][OTf]2 (3b) and [(η5-C5H4Me)2V(4-MeO-bian)][OTf]2 (4b) against human A549 lung adenocarcinoma cells were investigated by following membrane leakage of intracellular lactate dehydrogenase, Trypan Blue staining and activation of tumor protein p53 (p53). Evaluated complexes have a potent dose-dependent antiproliferative activity, causing cell cycle redistribution by the increased accumulation of cells in the G2 and S phase. In accord with the observed cell cycle deceleration, cyclin-dependent kinase inhibitor-interacting protein 1 (p21WAF1/Cip1), extracellular signal-regulated kinases 1 and 2 (ERK1/2), Checkpoint kinase 1 (Chk1), Checkpoint kinase 2 (Chk2) and their phosphorylated forms Chk1 at serine 345 and Chk2 at threonine 68 increased. In the cells exposed to complexes, dose- and time-dependent apoptotic process is initiated by the activation of the initiator caspase 8, followed by activation of effector caspase 3/7 and phosphatidylserine externalization. Moreover, because of treatment, A549 cells activate prosurvival mitogen-activated protein kinases (MAPK) signaling and up-regulate antiapoptotic protein B-cell lymphoma (Bcl-2), thereby promoting evasion of cell death. Both complexes exhibited considerably higher cytotoxic effect than the reference anticancer drug cis-platin and the cytotoxicity was more pronounced at higher treatment time.
- MeSH
- apoptóza účinky léků MeSH
- chelátory chemická syntéza chemie farmakologie MeSH
- kaspasy metabolismus MeSH
- komplexní sloučeniny chemická syntéza chemie farmakologie MeSH
- kontrolní body fáze G2 buněčného cyklu účinky léků MeSH
- lidé MeSH
- ligandy MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- vanad chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Reaction of vanadocene dichlorides (Cp(2)VCl(2) and (eta(5)-C(5)H(4)Me)(2)VCl(2)) with amino acids containing secondary amino groups gives three types of complexes: a) compounds with N,O-bonded amino acid, b) O-bonded amino acids and c) O,O-bonded amino acid. The complexes with N,O-bonded amino acid and O-bonded amino acids were observed in the case of l-proline and N-methylglycine (NMG). Reactions with N-phenylglycine (NPG) give O,O-chelates as the sole products. All three types of the complexes were characterized by spectroscopic methods. Structures of [(eta(5)-C(5)H(4)Me)(2)V(O-Pro)][BPh(4)], [Cp(2)V(O-Pro)(2)][PF(6)](2), [Cp(2)V(N,O-NMG)][BPh(4)].MeOH, [(eta(5)-C(5)H(4)Me)(2)V(N,O-NMG)][BPh(4)].MeOH, [Cp(2)V(O-NMG)(2)][Cl](2).2H(2)O, [(eta(5)-C(5)H(4)Me)(2)V(O-NMG)(2)][Cl](2).H(2)O and [(eta(5)-C(5)H(4)Me)(2)V(O,O-NPG)][BPh(4)] were determined by X-ray crystallography.
