The new diiron complexes [Fe2Cp2(CO)(L)(μ-CO){μ-CN(Me)(Cy)}]CF3SO3 (L = pyridine, 3a; 4-aminopyridine, 3b; 4-dimethylaminopyridine, 3c; 4-trifluoromethylpyridine, 3d; nicotinic acid, 4; Cp = η5-C5H5, Cy = C6H11 = cyclohexyl) were synthesized in moderate to high yields using two distinct synthetic routes from the precursors 1 (L = CO, for 4) and 2 (L = NCMe, for 3a-d), respectively. All products were characterized by IR and multinuclear NMR spectroscopy, and the structures of 3b and 3d were ascertained by X-ray diffraction studies. The behavior of the complexes in aqueous solutions (solubility, Log Pow, stability) was assessed using NMR and UV-Vis methods. The in vitro antiproliferative activity of 3a-c and 4 was evaluated against seven human cancer cell lines (A2780, A2780R, A549, MCF-7, PC3, HOS and HT-29) and one normal cell line (MRC-5), following 24 h of incubation (MTT test). Overall, 3-4 demonstrated stronger cytotoxicity than cisplatin, with 3c emerging as the most potent compound. The activity seems primarily linked to the inhibition of metabolic processes in the cancer cells, including depletion of reactive oxygen species (ROS) levels. However, subtle differences have been observed between the complexes, with 4 exerting its cytotoxicity through a distinct multimodal mechanism.

• Klíčová slova
• Bioorganometallic chemistry, Cellular effects, Diiron complexes, In vitro cytotoxicity, Metals in medicine, Pyridine ligand,
• MeSH
• antitumorózní látky * farmakologie   chemie   chemická syntéza   MeSH
• komplexní sloučeniny farmakologie   chemie   chemická syntéza   MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• proliferace buněk účinky léků   MeSH
• pyridiny * chemie   farmakologie   chemická syntéza   MeSH
• železo chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky * MeSH
• komplexní sloučeniny MeSH
• ligandy MeSH
• pyridine MeSH Prohlížeč
• pyridiny * MeSH
• železo MeSH

With the aim of tuning the magnetic anisotropy, a series of Co(ii) complexes with the general formula of complex cations [Co(L)X]+, where X = Br- (1); I- (2); NCO- (3); NCS- (4a); N3 - (5), and [Co(L)(NCS)2] (4b), (L = a 17-membered pyridine-based N3O2-macrocyclic ligand containing two pyridin-2-ylmethyl pendant arms) were prepared and thoroughly characterized. The molecular structures for all complexes showed strongly distorted geometry in between octahedral and trigonal prismatic. The magnetic studies confirmed substantial magnetic anisotropy with positive values of D, the axial zero-field splitting parameter, but E/D ratios close to 1/3. This was supported by theoretical CASSCF calculations showing no significant effect of the co-ligands. Complex 4b was found to behave as a field-induced SMM.

• Publikační typ
• časopisecké články MeSH

The replacement of one of the acetate pendant arms with a 2-methylpyridine-N-oxide group in the molecule of H4dota significantly alters the coordination properties of the ligand in Ln(III) complexes. The structural properties of the complexes are investigated both in solution and in the solid state. The variable-temperature 1H NMR spectra of Nd(III), Eu(III), and Yb(III) complexes show that the twisted-square-antiprismatic (TSA) isomer is strongly destabilized and suppressed in solution and the complexes exist mostly as the square-antiprismatic (SA) isomers (98% for Eu(III) at -35 degrees C). The exchange between the TSA and SA isomers is fast at room temperature compared to that of the NMR time scale. The flexibility of the six-membered chelate ring formed by coordination of the 2-methylpyridine-N-oxide group to the central ion allows two orientations of this pendant arm relative to the acetate arms: syn-SA (pyridine in the direction of the acetates) and anti-SA (pyridine opposite to the acetates). The syn-SA form was found in the X-ray structure of the Nd(III) complex; the anti-SA forms were found in the structures of Dy(III), Tm(III), and Yb(III) complexes. The UV-vis and 1H NMR spectra of the Eu(III) complex suggest that both forms are in dynamic equilibrium in solution. A derivatization of the pyridine-N-oxide group with a carboxylic group in the 4 position has no significant effect on the properties of the Ln(III) complexes.

• MeSH
• absorpce MeSH
• chelátory chemie   MeSH
• heterocyklické sloučeniny monocyklické chemie   MeSH
• isomerie MeSH
• krystalografie rentgenová MeSH
• lanthanoidy chemie   MeSH
• ligandy MeSH
• magnetická rezonanční spektroskopie MeSH
• organokovové sloučeniny chemie   MeSH
• pyridiny chemie   MeSH
• roztoky MeSH
• spektrofotometrie ultrafialová MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid MeSH Prohlížeč
• chelátory MeSH
• heterocyklické sloučeniny monocyklické MeSH
• lanthanoidy MeSH
• ligandy MeSH
• organokovové sloučeniny MeSH
• pyridine N-oxide MeSH Prohlížeč
• pyridiny MeSH
• roztoky MeSH

G-quadruplexes (G4) are stacked non-canonical nucleic acid structures found in specific G-rich DNA or RNA sequences in the human genome. G4 structures are liable for various biological functions; transcription, translation, cell aging as well as diseases such as cancer. These structures are therefore considered as important targets for the development of anticancer agents. Small organic heterocyclic molecules are well known to target and stabilize G4 structures. In this article, we have designed and synthesized 2,6-di-(4-carbamoyl-2-quinolyl)pyridine derivatives and their ability to stabilize G4-structures have been determined through the FRET melting assay. It has been established that these ligands are selective for G4 over duplexes and show a preference for the parallel conformation. Next, telomerase inhibition ability has been assessed using three cell lines (K562, MyLa and MV-4-11) and telomerase activity is no longer detected at 0.1 μM concentration for the most potent ligand 1c. The most promising G4 ligands were also tested for antiproliferative activity against the two human myeloid leukaemia cell lines, HL60 and K562.

• Klíčová slova
• FRET-melting, G-quadruplex, G4 ligands, antiproliferative activity, cancer, circular dichroism, diquinolinyl-pyridine, telomerase,
• MeSH
• antitumorózní látky chemická syntéza   farmakologie   MeSH
• buňky K562 MeSH
• chinoliny chemická syntéza   farmakologie   MeSH
• G-kvadruplexy * MeSH
• HL-60 buňky MeSH
• lidé MeSH
• ligandy MeSH
• pyridiny chemická syntéza   farmakologie   MeSH
• racionální návrh léčiv MeSH
• telomerasa antagonisté a inhibitory   MeSH
• vazba proteinů MeSH
• viabilita buněk účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• chinoliny MeSH
• ligandy MeSH
• pyridiny MeSH
• telomerasa MeSH

Two macrocyclic ligands derived from H4dota containing three acetate pendant arms and one 2-methylpyridine-N-oxide coordinating unit were synthesized. The ligand H3do3apy(NO) (H3L1, 10-[(1-oxidopyridin-2-yl)methyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid) contains an unsubstituted pyridine-N-oxide ring; the ligand H4do3apy(NO-C) (H4L2, 10-[(4-carboxy-1-oxidopyridin-2-yl)methyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid) is functionalized with a carboxylic group in the 4 position of the pyridine ring to allow attachment to other molecules. The ligands form octadentate (N4O4 environment) Ln(III) complexes, with one water molecule completing the coordination sphere in a capping position. The complexes are present in solution exclusively as square-antiprismatic isomers over the whole lanthanide series. The introduction of the carboxylic group to the pyridine-N-oxide unit in H4L2 has no significant effect on the hydration number (q = 1) and the water exchange rate of the [Gd(H2O)(L2)]- complex compared to the parent [Gd(H2O)(L1)] complex (water residence times: tauM = 39 ns for [Gd(H2O)(L1)] and tauM = 34 ns for [Gd(H2O)(L2)]- at 298 K).

• MeSH
• časové faktory MeSH
• dendrimery chemie   MeSH
• gadolinium chemie   MeSH
• heterocyklické sloučeniny monocyklické chemie   MeSH
• isomerie MeSH
• kyseliny karboxylové chemie   MeSH
• ligandy MeSH
• luminiscenční měření MeSH
• magnetická rezonanční spektroskopie MeSH
• magnetická rezonanční tomografie MeSH
• organokovové sloučeniny chemická syntéza   chemie   MeSH
• pyridiny chemie   MeSH
• voda chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid MeSH Prohlížeč
• dendrimery MeSH
• gadolinium MeSH
• heterocyklické sloučeniny monocyklické MeSH
• kyseliny karboxylové MeSH
• ligandy MeSH
• organokovové sloučeniny MeSH
• pyridine N-oxide MeSH Prohlížeč
• pyridiny MeSH
• voda MeSH

This study presents an improved synthetic route to ligand (S)-4-(tert-butyl)-2-(5-(trifluoromethyl)pyridin-2-yl)-4,5-dihydrooxazole and its application as a highly active and enantioselective catalyst in the addition of arylboronic acids to cyclic N-sulfonylketimines. Immobilization of such a ligand was achieved using a commercially available starting material and a PS-PEG TentaGel S NH2 support, resulting in a stable heterogeneous catalyst. Although the anchored catalyst exhibited a slight reduction in enantioselectivity and a 4-fold decrease in reaction rate, it displayed remarkable stability, enabling 10 consecutive reaction cycles. Furthermore, the successful transition to a continuous flow system demonstrated even higher turnover numbers compared to batch arrangements. These findings provide valuable insights into the development of efficient flow reactors for continuous synthesis of benzosultams, further advancing the field of asymmetric catalysis.

• Publikační typ
• časopisecké články MeSH

Given its five unpaired d-electrons, long electronic relaxation time, and fast water exchange, Mn(2+) is a potential candidate for contrast agent application in medical magnetic resonance imaging. Nevertheless, the design of chelators that ensure stable Mn(2+) complexation and optimal relaxation properties remains a coordination chemistry challenge. Here, we report the synthesis of two pyridine-containing ligands L1 and L2, with 15-membered triaza-dioxa-crown and pentaaza-crown ether macrocycles, respectively, and the characterization of their Mn(2+) complexes. Protonation constants of the ligands and stability constants of various metal complexes were determined by potentiometry. The presence of the pyridine in the macrocyclic ring induces rigidity of the complexes which results in a greater thermodynamic stability with respect to the nonpyridine analogues. Solid-state structures of MnL1 and MnL2 confirmed seven-coordination of Mn(2+) with Cl(-) and H(2)O in axial positions. The dissociation kinetics of MnL2 in the presence of Zn(2+) were followed by relaxometric measurements. They proved the prime importance of the proton-assisted dissociation while the zinc(II)-assisted pathway is not important at physiological pH. For MnL1, the dissociation was too fast to be studied by conventional relaxivity measurements under pH 6. A combined (17)O NMR and (1)H NMRD study on MnL1 and MnL2 yielded the parameters that govern the relaxivity of these complexes. The water exchange rate for MnL1, k(ex)(298) = 0.38 x 10(7) s(-1), is the lowest value ever reported for a Mn(2+) complex, while a considerably higher value was obtained for MnL2 (k(ex)(298) = 6.9 x 10(7) s(-1)). Anion binding was studied by relaxometric titrations. They revealed weak interactions between MnL2 and phosphate or citrate, leading to the formation of monohydrated species. Overall, the incorporation of a pyridine into a polyaza macrocycle scaffold has several beneficial effects on the Mn(2+) chelates with respect to potential MRI contrast agent applications: (i) The thermodynamic and the kinetic stability of the complexes is increased. (ii) The rigidified ligand backbone results in higher coordination numbers of the metal ion, allowing for two inner-sphere water molecules in aqueous solution.

• MeSH
• elektrochemie MeSH
• kinetika MeSH
• krystalografie rentgenová MeSH
• magnetická rezonanční spektroskopie MeSH
• makrocyklické sloučeniny chemie   MeSH
• molekulární modely MeSH
• pyridiny chemie   MeSH
• sloučeniny manganu chemie   MeSH
• termodynamika MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• makrocyklické sloučeniny MeSH
• pyridine MeSH Prohlížeč
• pyridiny MeSH
• sloučeniny manganu MeSH

This article provides an overview of compounds based on imidazo[1,2-a]pyridine, imidazo[1,5-a]pyridine, imidazo[4,5-b]pyridine and imidazo[4,5-c]pyridine scaffolds, which act as potent ligands of diverse molecular targets localized in the central nervous system. A literature survey revealed that various imidazopyridines can be powerful modulators of several diseases associated with CNS dysfunction including Alzheimer's disease, Parkinson's disease, schizophrenia, depression or sleeping disorders. A description of target enzymes (e.g., β-secretase, γ-secretase, fatty acid amide hydrolase - FAAH, leucine-rich repeat kinase 2 - LRRK2) and selected receptors (e.g., GABA-A, histamine H3, serotonin 5-HT3, 5-HT4, 5-HT6, dopamine D4, adenosine A2A, orexin), modes of action of imidazopyridine-based ligands and their therapeutic importance is discussed.

• Klíčová slova
• Imidazo[1,2-a]pyridine, Imidazo[1,5-a]pyridine, Imidazo[4,5-b]pyridine, Imidazo[4,5-c]pyridine, Neurodegenerative disorders, Neurological disorders, Sleeping disorders,
• MeSH
• cílená molekulární terapie MeSH
• duševní poruchy farmakoterapie   MeSH
• imidazoly chemie   farmakologie   terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• ligandy MeSH
• neurodegenerativní nemoci farmakoterapie   MeSH
• pyridiny chemie   farmakologie   terapeutické užití   MeSH
• racionální návrh léčiv * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• imidazoly MeSH
• imidazopyridine MeSH Prohlížeč
• ligandy MeSH
• pyridiny MeSH

Polyamidoamine dendrimers (PAMAMs) of generations 1 (G1) and 4 (G4) were conjugated with a bifunctional pyridine-N-oxide DOTA analog, 10-[(4-carboxy-1-oxidopyridin-2-yl)methyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (H(4)do3a-py(NO-C)), through the pyridine-4-carboxylic acid group, and the conjugates were radiolabeled with indium-111. Reaction conditions for the radiolabelling were optimized. Both radiolabeled conjugates, G1-[(111)In(do3a-py(NO-C))] and G4-[(111)In(do3a-py(NO-C))], were kinetically stable for at least 48h after preparation; in the presence of competitive ligands, the radiochemical purity of the conjugates slightly decreased (4-7%) over the same time period. The preclinical pharmacokinetics of both agents were evaluated. Biodistribution and elimination in rats were more favorable for the G1-[(111)In(do3a-py(NO-C))] conjugate than G4-[(111)In(do3a-py(NO-C))] conjugate. However, the G1-[(111)In(do3a-py(NO-C))] conjugate was rapidly eliminated from the body, mainly through urine, while, significant and long-term radioactivity uptake in the liver and kidney was observed for the G4-[(111)In(do3a-py(NO-C))] conjugate.

• MeSH
• dendrimery chemie   farmakokinetika   MeSH
• heterocyklické sloučeniny monocyklické chemie   farmakokinetika   MeSH
• izotopové značení metody   MeSH
• krysa rodu Rattus MeSH
• nosiče léků chemie   farmakokinetika   MeSH
• potkani Wistar MeSH
• pyridiny chemie   farmakokinetika   MeSH
• radiofarmaka chemie   farmakokinetika   MeSH
• radioizotopy india chemie   farmakokinetika   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid MeSH Prohlížeč
• dendrimery MeSH
• heterocyklické sloučeniny monocyklické MeSH
• nosiče léků MeSH
• PAMAM Starburst MeSH Prohlížeč
• pyridine N-oxide MeSH Prohlížeč
• pyridiny MeSH
• radiofarmaka MeSH
• radioizotopy india MeSH

A new 15-membered pyridine-based macrocyclic ligand containing one acetate pendant arm (N-carboxymethyl-3,12,18-triaza-6,9-dioxabicyclo[12.3.1]octadeca-1(18),14,16-triene, L1) was synthesized and its Mn(II) complex MnL1 was investigated in the context of MRI contrast agent development. The X-ray molecular structure of MnL1 confirmed a coordination number of seven with an axially compressed pentagonal bipyramidal geometry and one coordination site available for an inner-sphere water molecule. The protonation constants of L1 and the stability constants of Mn(II), Zn(II), Cu(II) and Ca(II) complexes were determined by potentiometry, and revealed higher thermodynamic stabilities in comparison with complexes of 15-pyN3O2, the parent macrocycle without an acetate pendant arm. The MnL1 complex is fully formed at physiological pH 7.4, but it shows fast dissociation kinetics, as followed by relaxometry in the presence of an excess of Zn(II). The short dissociation half-life estimated for physiological pH (ca. 3 minutes) is related to fast spontaneous dissociation of the non-protonated complex. At lower pH values, the proton-assisted dissociation pathway becomes important, while the Zn(II) concentration has no effect on the dissociation rate. 17O NMR and 1H NMRD data indicated the presence of one inner-sphere water molecule with a rather slow exchange (k298ex = 4.5 × 106 s-1) and provided information about other microscopic parameters governing relaxation. The relaxivity (r1 = 2.45 mM-1 s-1 at 20 MHz, 25 °C) corresponds to typical values for monohydrated Mn(II) chelates. Overall, the acetate pendant arm in L1 has a beneficial effect with respect to 15-pyN3O2 in increasing the thermodynamic stability and kinetic inertness of its Mn(II) complex, but leads to a reduced number of inner-sphere water molecules and thus lower relaxivity.

• Publikační typ
• časopisecké články MeSH