Effect of Microwave Irradiation on the Condensation of 6-Substituted 3-Formylchromones with Some Five-membered Heterocyclic Compounds

Lácová, Margita; Gašparová, Renata; Loos, Dušan; Liptay, Tibor; Prónayová, Naďa

doi:10.3390/50200167

Cited by 28 publications

(25 citation statements)

References 13 publications

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“…13 The latter was carried out either under reflux in acetic acid or by using microwave assisted conditions. [14][15][16] The compounds were obtained with average yields ranging from 80 to 96 %. The details of the experimental conditions are reported as supplementary information.…”

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confidence: 99%

Anthrax Lethal Factor Protease Inhibitors: Synthesis, SAR, and Structure-Based 3D QSAR Studies

et al. 2005

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We have recently identified a series of compounds which efficiently inhibit Anthrax lethal factor (LF) metallo-protease. Here we present further structure activity relationship and CoMFA (Comparative Molecular Field Analysis) studies on newly derived inhibitors. The obtained 3D QSAR model was subsequently compared with the X-ray structure of the complex between LF and a representative compound. Our studies form the basis for the rational design of additional compounds with improved activity and selectivity.Anthrax is an infectious disease caused by the bacterium Bacillus anthracis. 1 This rod shaped bacterium infects humans through the respiratory system, skin, or digestive tract. Dependent upon the entry route into the human body, Anthrax can be highly lethal. Although cutaneous Anthrax is rarely lethal, inhalation Anthrax is dangerous and usually fatal. 2 Upon inhalation, the Anthrax spores adhere to the alveolar macrophages and germinate. Bacteria migrate to the lymph node, in which they rapidly multiply and excrete a tripartite exotoxin comprised of protective antigen (PA, 83 kDa), lethal factor (LF, Zn 2+ -metalloproteinase, 90 kDa) and calmodulin-activated edema factor adenylate cyclase (EF, 89 kDa). 3,4 The combined actions of these proteins constitute the Anthrax toxins (AT) which induce cell death. Unless properly and promptly treated, inhalation anthrax will lead to the death of the host organism. 5 Initially, PA binds to an AT receptor on the host cell surface, where it is cleaved by a furinlike protease to produce a 20 kDa N-terminal fragment (PA 20 ) and a 63 kDa C-terminal fragment (PA 63 ). 6 PA 63 , which remains bound to the membrane, oligomerizes into a heptameric prepore capable of binding LF and EF. 7 Upon binding of LF and EF, the complex undergoes receptor mediated endocytosis and the PA 63 conformational change allows the two enzymatic moieties LF and EF to translocate into the cell cytosol. Once in the cytosol, LF is then able to cleave several members of the MAPKK family near the Nterminus. [8][9][10] This cleavage prevents interaction with, and phosphorylation of, downstream MAPK, thereby inhibiting one or more signaling pathways through a mechanism not yet understood. 11 * To Whom Correspondence should be addressed. With the long term goal of developing novel potential treatments for Anthrax disease, we previously identified several small molecule inhibitors that inhibit Anthrax LF protease activity with IC 50 's in sub-micromolar range. 12 Cell based and peptide cleavage assays were subsequently used to confirm the potency of the iterate leads. The most potent compounds were subsequently tested in mice models of the diseases showing a protection against Bacillus anthracis spores, when used in combination with the antibiotic ciproflaxin. 12 Initial structure activity relationship (SAR) data suggested that the presence of multiple substitutions on the phenyl ring significantly increases the inhibitory activity. 12 Furthermore, details of the 3D structure of the complex between ...

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confidence: 99%

Anthrax Lethal Factor Protease Inhibitors: Synthesis, SAR, and Structure-Based 3D QSAR Studies

et al. 2005

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“…Refluxing 1a with pyrazolinyltriazinylacetonitrile (83) in ethanol containing few drops of piperidine gave the condensation product 84 in 95% yield, as antitumor agent (Scheme 40) [68] .…”

Section: Scheme 39mentioning

confidence: 99%

“…While, 2-acetamido-1-methyl-5-[(6-substituted 4-oxo-chromen-3-yl)methylidene]-4,5-dihydroimidazol-4-one 114 was obtained when the reaction took place in acetic anhydride and potassium acetate (Scheme 55) [83].…”

Section: Scheme 54mentioning

confidence: 99%

3-Formylchromones as diverse building blocks in heterocycles synthesis

et al. 2013

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“…Insulin released into the medium was assayed with a radioimmunoassay using rat insulin (Novo Nordisk, Bagsvaerd, Denmark) as a standard, (mono 125 I-Tyr A 14 )-insulin as the labeled compound (Sanofi-Aventis, Germany), and anti-insulin antibodies from Linco (St. Louis, MO, USA). Each compound had been checked for noninterference with the insulin radioimmunoassay.…”

Section: Insulin Releasementioning

confidence: 99%

Synthesis and antidiabetic activity of some new chromonyl-2,4-thiazolidinediones

Ceylan–Ünlüsoy

Verspohl

Ertan

2010

Journal of Enzyme Inhibition and Medicinal Chemistry

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Effect of Microwave Irradiation on the Condensation of 6-Substituted 3-Formylchromones with Some Five-membered Heterocyclic Compounds

Cited by 28 publications

References 13 publications

Anthrax Lethal Factor Protease Inhibitors: Synthesis, SAR, and Structure-Based 3D QSAR Studies

Anthrax Lethal Factor Protease Inhibitors: Synthesis, SAR, and Structure-Based 3D QSAR Studies

3-Formylchromones as diverse building blocks in heterocycles synthesis

Synthesis and antidiabetic activity of some new chromonyl-2,4-thiazolidinediones

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