Pottova bolest ekstrapulmonalni je koštano-zglobni oblik tuberkuloze kod koje bacili Mycobacterium tuberculosis uzrokuju osteomijelitis kralježaka. Kod Pottove bolesti dolazi do razvoja kroničnog ...apscesa koji se još naziva i hladni apsces zbog odsutnosti boli i drugih znakova upale. Ako se hladni apsces razvije u području cervikalne kralježnice, može doći do njegova širenja prema stražnjoj stijenci ždrijela kroz duboke vratne prostora smještene anteriorno od cervikalnih kralježaka. U našem radu prikazujemo slučaj bolesnice s apscesom dubokih vratnih prostora koji je uzrokovan Pottovom bolešću cervikalne kralježnice. Apsces se prezentirao kao izbočina na stražnjoj stijenci ždrijela udružena s otežanim gutanjem, disanjem, inspiratornim stridorom i tetraparezom.
Pott’s disease is an extrapulmonary skeletal manifestation of tuberculosis infection in which the Mycobacterium tuberculosis bacilli cause the development of vertebral osteomyelitis. Pott’s disease is associated with developing a chronic abscess often called a cold abscess due to the absence of pain and other signs of inflammation. If a cold abscess is developed in the cervical spine, it can spread to the posterior pharynx wall through deep neck spaces located anteriorly to the cervical vertebra. This paper presents a patient with a deep neck space abscess caused by the cervical spine Pott’s disease. The abscess was presented as a bulging of the posterior wall of the pharynx associated with difficulty swallowing and breathing, inspiratory stridor, and tetraparesis.
Pottova bolest ekstrapulmonalni je koštano-zglobni oblik tuberkuloze kod koje bacili Mycobacterium
tuberculosis uzrokuju osteomijelitis kralježaka. Kod Pottove bolesti dolazi do razvoja kroničnog ...apscesa
koji se još naziva i hladni apsces zbog odsutnosti boli i drugih znakova upale. Ako se hladni apsces razvije
u području cervikalne kralježnice, može doći do njegova širenja prema stražnjoj stijenci ždrijela kroz
duboke vratne prostora smještene anteriorno od cervikalnih kralježaka. U našem radu prikazujemo slučaj
bolesnice s apscesom dubokih vratnih prostora koji je uzrokovan Pottovom bolešću cervikalne kralježnice.
Apsces se prezentirao kao izbočina na stražnjoj stijenci ždrijela udružena s otežanim gutanjem, disanjem,
inspiratornim stridorom i tetraparezom.
A series of novel 2,6-diphenyl substituted imidazo4,5-bpyridines was designed and synthesized using optimized Suzuki cross coupling to evaluate their biological activity in vitro. The conditions of ...the Suzuki coupling were evaluated and optimized using a model reaction. To study the influence of the substituents on the biological activity, we prepared N-unsubstituted and N-methyl substituted imidazo4,5-bpyridines with different substituents at the para position on the phenyl ring placed at position 6 on the heterocyclic scaffold. Antiproliferative activity was determined on diverse human cancer cell lines, and the selectivity of compounds with promising antiproliferative activity was determined on normal peripheral blood mononuclear cells (PBMC). Pronounced antiproliferative activity was observed for p-hydroxy substituted derivatives 13 and 19, both displaying strong activity against most of the tested cell lines (IC50 1.45–4.25 μM). The unsubstituted N-methyl derivative 19 proved to be the most active derivative. There was a dose-dependent accumulation of G2/M arrested cells in several cancer cell lines after exposure to compound 19, implying a cell cycle-phase-specific mechanism of action. Additionally, the novel series of derivatives was evaluated for antiviral activity against a broad panel of viruses, yet the majority of tested compounds did not show antiviral activity.
A novel series of tetracyclic imidazo4,5-bpyridine derivatives was designed and synthesized as potential antiproliferative agents. Their antiproliferative activity against human cancer cells was ...influenced by the introduction of chosen amino side chains on the different positions on the tetracyclic skeleton and particularly, by the position of N atom in the pyridine nuclei. Thus, the majority of compounds showed improved activity in comparison to standard drug etoposide. Several compounds showed pronounced cytostatic effect in the submicromolar range, especially on HCT116 and MCF-7 cancer cells. The obtained results have confirmed the significant impact of the position of N nitrogen in the pyridine ring on the enhancement of antiproliferative activity, especially for derivatives bearing amino side chains on position 2. Thus, regioisomers 6, 7 and 9 showed noticeable enhancement of activity in comparison to their counterparts 10, 11 and 13 with IC50 values in a nanomolar range of concentration (0.3–0.9 μM). Interactions with DNA (including G-quadruplex structure) and RNA were influenced by the position of amino side chains on the tetracyclic core of imidazo4,5-bpyridine derivatives and the ligand charge. Moderate to high binding affinities (logKs = 5–7) obtained for selected imidazo4,5-bpyridine derivatives suggest that DNA/RNA are potential cell targets.
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•Novel tetracyclic imidazo4,5-bpyridine derivatives.•Improved antiproliferative activity in comparison to drug etoposide.•Impact of the N position in pyridine ring on the activity.•IC50 values in nanomolar range of concentration (0.3–0.9 μM).•Interactions with DNA (including G-quadruplex structure) and RNA.
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•New imidazo4,5-bpyridine derived iminocoumarins are prepared and their pH sensing potential evaluated in different solvents.•Inspected experimental conditions include nine solvents ...with different polarities and buffered water with defined pH values.•Photophysical characterization and acid/base properties are determined with UV–Vis and fluorescence spectroscopies.•DFT data show all systems are monoprotonated at neutral pH and transit among diprotonated and neutral forms with pH changes.•Transition pH values are fine tuned with a single substitution on the iminocoumarin core, confirming a useful design strategy.
We describe the synthesis, spectroscopic characterization and computational analysis of the protonation equilibria of several newly designed imidazo4,5-bpyridine derived iminocoumarins to confirm their potential as pH sensing molecules in different solvents. The photophysical characterization and acid/base properties of these chromophores have been carried out in several polar and non-polar organic solvents as well as buffered aqueous solution with different pH values using UV–Vis and fluorescence spectroscopies. Obtained results revealed that both the solvent polarity and the electronic nature of substituents placed at the iminocoumarin and imidazo4,5-bpyridine cores significantly influence spectral responses of studied systems. An excellent agreement in experimentally measured and computationally determined pKa values and electronic excitations suggests that all systems are monoprotonated cations at neutral pH, while their transition to diprotonated forms occurs at pH values between 3.4 and 4.4, whereas they get reverted to neutral unionized molecules between 10.4 and 13.7. These small differences in narrow ranges of borderline pH values are predominantly brought about by variations in a single substituent on the iminocoumarin core, thereby allowing a simple strategy to further modify the observed sensing features and easily tune them for a specific application.
A series of cyano- and amidino-substituted imidazo4,5-
pyridines were synthesized using standard methods of organic synthesis, and their biological activity was evaluated. Biological evaluation ...included in vitro assessment of antiproliferative effects on a diverse selection of human cancer cell lines, antibacterial activity against chosen Gram-positive and Gram-negative bacterial strains, and antiviral activity on a broad panel of DNA and RNA viruses. The most pronounced antiproliferative activity was observed for compound
, which contained an unsubstituted amidino group, and compound
, which contained a 2-imidazolinyl amidino group; both displayed selective and strong activity in sub-micromolar inhibitory concentration range against colon carcinoma (IC
0.4 and 0.7 μM, respectively). All tested compounds lacked antibacterial activity, with the exception of compound
, which showed moderate activity against
(MIC 32 μM). Bromo-substituted derivative
, which contained an unsubstituted phenyl ring (EC
21 μM), and
-cyano-substituted derivative
(EC
58 μM) showed selective but moderate activity against respiratory syncytial virus (RSV).
Herein, we present the design, synthesis, and biological activity of novel iminocoumarin imidazo4,5-
b
pyridine derivatives. The prepared compounds were designed to study the type of substituent in ...position 6 of the coumarin nucleus as well as the type of the substituent at the N atom of imidazo4,5-
b
pyridine core for their effect on the biological activity. Therefore, all compounds were tested for their antiproliferative action on several human cancer cell lines
in vitro
, for their antioxidative activity, antibacterial activity on several bacterial strains, and for their antiviral activity on several viruses. The results of the evaluation of biological activity revealed that the tested derivatives did not display significant biological activities. The majority of the tested compounds were not active at all, while some derivatives showed low activity in these assays. Therefore, we could conclude that the biological potential of 6-substituted iminocoumarin derivatives is very low – the substitution in position 6 of the coumarin nucleus, in comparison to 7-substituted iminocoumarins, strongly decreases biological activity.
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•novel N-substituted imidazo4,5-bpyridine derived acrylonitriles.•strong antiproliferative activity in submicromolar range of concentrations (IC50 0.2 – 0.6 μM)•immunofluorescence ...staining and tubulin polymerization assays confirmed tubulin as the main target.•colchicine-binding site is excluded as a potential interacting unit.•mechanism of action supported by the computational analysis.•21 potently inhibited cancer cell migration and did not affect the viability of normal cells.
Imidazo4,5-bpyridine derived acrylonitriles were synthesized and explored for their in vitro antiproliferative effect on a diverse human cancer cell line panel. Three compounds, 20, 21 and 33, showed strong activity in the submicromolar range (IC50 0.2–0.6 μM), and were chosen for further biological experiments. Immunofluorescence staining and tubulin polymerization assays confirmed tubulin as the main target, but excluded its colchicine-binding site as a potential interacting unit. This was supported by the computational analysis, which revealed that the most potent ligands act on the extended colchicine site on the surface between interacting tubulin subunits, where they interfere with their polymerization and reveal pronounced antitumor properties. In addition, lead molecule 21 potently inhibited cancer cell migration, while it did not affect the viability of normal cells even at the highest concentration tested (100 µM).
We present the design, synthesis, computational analysis, and biological assessment of several acrylonitrile derived imidazo4,5-bpyridines, which were evaluated for their anticancer and antioxidant ...properties. Our aim was to explore how the number of hydroxy groups and the nature of nitrogen substituents influence their biological activity. The prepared derivatives exhibited robust and selective antiproliferative effects against several pancreatic adenocarcinoma cells, most markedly targeting Capan-1 cells (IC50 1.2–5.3 μM), while their selectivity was probed relative to normal PBMC cells. Notably, compound 55, featuring dihydroxy and bromo substituents, emerged as a promising lead molecule. It displayed the most prominent antiproliferative activity without any adverse impact on the viability of normal cells. Furthermore, the majority of studied derivatives also exhibited significant antioxidative activity within the FRAP assay, even surpassing the reference molecule BHT. Computational analysis rationalized the results by highlighting the dominance of the electron ionization for the antioxidant features with the trend in the computed ionization energies well matching the observed activities. Still, in trihydroxy derivatives, their ability to release hydrogen atoms and form a stable O–H⋯O•⋯H–O fragment upon the H• abstraction prevails, promoting them as excellent antioxidants in DPPH• assays as well.
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We prepared a range of N-arylbenzamides with a variable number of methoxy and hydroxy groups, bearing either amino or amino-protonated moieties, and used DPPH and FRAP assays to evaluate their ...antioxidant capacity. Most of the systems exhibit improved antioxidative properties relative to the reference BHT molecule in both assays. Combining results from both sets of experiments, the most promising antioxidative potential was displayed by the trihydroxy derivative 26, which we propose as a lead compound for a further optimization of the benzamide scaffold. Computational analysis helped in interpreting the observed trends and demonstrated that protonated systems are better antioxidants than their neutral counterparts, while underlying the positive influence of the electron-donating methoxy group on the antioxidant properties, thus confirming the experiments. It also revealed that the introduction of the hydroxy groups shifts the reactivity from both amide and amine groups toward this moiety and additionally enhances antioxidative features. This is particularly evident in 26H•+ , which owes its pronounced reactivity to the stabilizing O•···H–O hydrogen bonding between the created phenoxyl radical and the two neighboring hydroxy groups. We demonstrated that its antioxidative activities are more favorable than those for analogous trihydroxy derivatives without the N-phenyl group or without the amide moiety, which strongly justifies the employed strategy in utilizing bisphenylamides in designing potent antioxidants.
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