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The beta2 Integrin Mac-1 Induces Protective LC3-Associated Phagocytosis of Listeria monocytogenes

The intracellular pathogen Listeria monocytogenes (L.m.) is targeted by the autophagic machinery, but the molecular mechanisms involved and consequences for anti-listerial immunity remain enigmatic. Here, we demonstrate that L.m. infection of macrophages in vivo exclusively evokes LC3-associated phagocytosis (LAP), but not canonical autophagy, and that targeting of L.m. by LAP is required for anti-listerial immunity. The pathway leading to LAP induction in response to L.m. infection emanates from the beta2 integrin Mac-1 (CR3, integrin alphaMbeta2), a receptor recognizing diverse microbial ligands. Interaction of L.m. with Mac-1 induces acid sphingomyelinase-mediated changes in membrane lipid composition that facilitate assembly and activation of the phagocyte NAPDH oxidase Nox2. Nox2-derived reactive oxygen species then trigger LC3 recruitment to L.m.-containing phagosomes by LAP. By promoting fusion of L.m.-containing phagosomes with lysosomes, LAP increases exposure of L.m. to bactericidal acid hydrolases, thereby enhancing anti-listerial activity of macrophages and immunity of mice. Listeria monocytogenes are targeted by the autophagic machinery via unclear molecular mechanisms. Gluschko and Herb et al. demonstrate that LC3-associated phagocytosis, but not canonical autophagy, is required for elimination of L. monocytogenes by macrophages and activated by the beta2 integrin Mac-1 (CR3, integrin alphaMbeta2).

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N561 – PubChem

The important role of 6-Amino-2,3-dihydrophthalazine-1,4-dione

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Chemiluminescence of phthalhydrazide derivatives in organized media: Interactions with surfactants and cyclodextrins

The chemiluminescent oxidation of some phthalhydrazide derivatives, luminol (LUM), isoluminol (ISOL), N-(4-aminobutyl)-N-ethylisoluminol (ABEI) and N-(6-aminohexyl)-N-ethylisoluminol (AHEI), has been carried out in micellar media and in the presence of natural cyclodextrins (CDs), using Co(II) as catalyst and H2O2 as oxidant. The cationic cetyltrimethylammonium bromide (CTAB) and, in a lesser extent, the anionic sodium dodecyl sulfate (SDS) produce quenching in the chemiluminescence (CL) of all the luminophores at concentrations above the cmc, whereas slight enhancements are attained with the non-ionic pentaethylene glycol monododecyl ether (C12E5). On the contrary, the incorporation of the CDs to the reaction produces a remarkable intensification of the CL. Binding of the luminophores to the macrocycles and the micelles has been studied by Pulsed-Gradient-Spin-Echo-NMR (PGSE-NMR) and fluorescence anisotropy. The cationic CTAB decreases the emission mainly due to charge compensation as a result of the association of the luminophores and the luminescent intermediates to the micelles. The presence of the alkyl substituents of ABEI and AHEI provides an additional hydrophobic contribution to the binding process. SDS quenches this reaction as the micelles retain Co(II) on their anionic layer. The protection and stabilization of these luminophores or their luminescent intermediates provided by the cavities of the CDs make this family of cyclic oligosaccharides much more suitable agents than the surfactants for enhancing the CL in aqueous media for this specific reaction.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N602 – PubChem

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Total syntheses of menisporphine and daurioxoisoporphine c enabled by photoredox-catalyzed direct C-H arylation of isoquinoline with aryldiazonium Salt

Isoquinoline alkaloids are attractive natural products due to their diverse chemical structures as well as remarkable bioactivities. Herein, we report the concise total syntheses of two isoquinoline alkaloids, menisporphine and daurioxoisoporphine C, through a mild and efficient photoredox-catalyzed direct C-H arylation of isoquinoline core with aryldiazonium salt. This new strategy is complementary to the conventional isoquinoline synthesis and would provide us a useful means to achieve a more convergent and flexible approach to access diverse isoquinoline structures.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N507 – PubChem

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Microwave assisted reactions of some azaheterocylic compounds

A fast, general, environmentally friendly and facile method for preparation of five- and six-membered ring diazaheterocylic salts under microwave irradiation is presented. The N-alkylation reactions of imidazole, pyrimidine, pyridazine and phthalazine have been studied. The microwaves remarkably accelerated these N-alkylations, the reaction times decreased dramatically, the reaction conditions were milder, the consumed energy decreased considerably and the amount of solvents used was reduced substantially. Consequently, the microwave assisted alkylation of N-containing heterocycles could be considered eco-friendly. In some cases, under MW irradiation the yields are also higher. A comparative study of microwave vs. classical conditions (liquid solvents) has been done. Twelve new diazaheterocylic salts of potential practical interest were obtained.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N500 – PubChem

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Synthesis and biological evaluation of 2,4-Diaminopyrimidine-based antifolate drugs against bacillus anthracis

Due to the innate ability of bacteria to develop resistance to available antibiotics, there is a critical need to develop new agents to treat more resilient strains. As a continuation of our research in this area, we have synthesized a series of racemic 2,4-diaminopyrimidine-based drug candidates, and evaluated them against Bacillus anthracis. The structures are comprised of a 2,4-diaminopyrimidine ring, a 3,4-dimethoxybenzyl ring, and an N-acryloyl-substituted 1,2-dihydrophthalazine ring. Various changes were made at the C1 stereocenter of the dihydrophthalazine moiety in the structure, and the biological activity was assessed by measurement of the MIC and Ki values to identify the most potent drug candidate.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N313 – PubChem

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Aryl-fused and hetaryl-fused-2,4-diazepine and 2,4-diazocine antiarrhythmic agents

Aryl-fused- and hetaryl-fused-2,4-diazepines of formula XXXVI, benzodiazocines of formula XXX, benzodiazepines of formula II STR1 delta-aminoamides of formula III and aryldimethanamines of formula XXXVII STR2 wherein A is an aryl or hetaryl ring; R1 is hydrogen, alkyl, aryl or hetaryl; R2 is hydrogen, alkyl, substituted alkyl, or aryl; R3 is alkyl, aryl, aralkyl or heteroatom substituted alkyl or aralkyl; R4 is hydrogen or alkyl; R5 is hydrogen, alkyl, aryl or hetaryl; R6 is hydrogen, alkyl, alkoxy, halogen or a fused benzene ring; R9 is hydrogen, alkyl, or substituted alkyl; and R10 is hydrogen, alkyl, or substituted alkyl. The invention further relates to processes for the preparation of, pharmaceutical compositions containing, and methods of treating cardiac arrhythmia with the compounds of formulas XXXVI, XXX, II, III, and XXXVII.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N10 – PubChem

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Iron-catalyzed Minisci acylation of N-heteroarenes with alpha-keto acids

An efficient and mild protocol has been developed for the Minisci acylation reactions of nitrogen-containing heteroarenes with alpha-keto acids. Distinct from the conventional Minisci acylation conditions, the chemistry was performed using non-noble metal Fe(II), instead of expensive Ag(I) salt, as catalyst. A wide range of substrates, including aliphatic or aromatic alpha-keto acids, as well as various N-heteroarenes, proved to be compatible with the protocol. Scale-up experiment also demonstrates the practicality of the approach.

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Reference£º
Phthalazine – Wikipedia,
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Chemiluminescent immunoassay technology: what does it change in autoantibody detection?

Diagnostic technology is rapidly evolving, and over the last decade, substantial progress has been made even for the identification of antibodies, increasingly approaching this type of diagnostic to that of automated clinical chemistry laboratory. In this review, we describe the analytical and diagnostic characteristics of chemiluminescence technology in its strength and in its applicability for a more rapid and accurate diagnosis of autoimmune diseases. The wide dynamic range, greater than that of immunoenzymatic methods, the high sensitivity and specificity of the results expressed in quantitative form, the high degree of automation and the clinical implications related to the reduction in the turnaround time, and the ability to run a large number of antibody tests (even of different isotypes), directed towards large antigenic panels in random access mode, make this technology the most advanced in the clinical laboratory, with enormous repercussions on the workflow and on the autoimmunology laboratory organisation. Further improvements are expected in the coming years with the development of new analytical platforms such as the flow-injection chemiluminescent immunoassay, the two-dimensional resolution for chemiluminescence multiplex immunoassay and the magnetic nanoparticles chemiluminescence immunoassay, which will likely result in additional increases in the clinical efficacy of antibody tests.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N540 – PubChem

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In vitro effects of very low levels of aflatoxin B1 on free radicals production and bactericidal activity of bovine blood neutrophils

As one of the most potent and hazardous feed/food-originated mycotoxins, aflatoxin (AF) B1 is regarded as a potent immunosuppressor in dairy cows. Neutrophils (PMN), as key effector cells against pathogens, have a high potential to kill engulfed microbes. To investigate the in vitro effects of very low doses of AFB1 on blood PMN functions, we examined the effects of biologically relevant concentrations of AFB1 on the phagocytosis and non-phagocytosis dependent luminol, representative of mainly intracellular free radicals, and isoluminol, representative of mainly extracellular free radicals, chemiluminescence (CL), necrosis and apoptosis of PMN. Isolated blood PMN from healthy dairy cows (n=12) were exposed to 0, 0.01, 0.05 and 0.5ng/ml of AFB1 for 0.5 and 18h depending on the assay. Further, blood PMN of healthy dairy cows (n=8) were exposed to 0.5ng/ml of AFB1 for 3h and myeloperoxidase (MPO) activity, superoxide anion (O2-) production, phagocytosis and killing activities against Staphylococcus (S.) aureus and Escherichia (E.) coli, were examined. Though the effect of extremely low doses of AFB1 were less pronounced, at 0.5ng/ml the production of free radicals was greatly enhanced, especially extracellularly. In contrast to isoluminol CL, the AFB1-treated PMN showed a remarkably impaired phagocytosis-depended luminol CL. PMN necrosis and apoptosis were not affected by AFB1. MPO activity, O2- production, phagocytosis rates and killing of E. coli and S. aureus by AFB1-treated PMN were significantly lower than those of non-treated ones. Our results show the extracellularly pro-oxidant and antiphagocytic properties of very low doses of AFB1 for bovine PMN. The scope of the suppressive effects of the in vitro AFB1 levels on cellular innate immune functions should be considered for high yielding dairy cows.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N605 – PubChem

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Chapter 5 Chemiluminescence immunoassays: the early work

At this stage it is possible to appreciate the early developments in chemiluminescence immunoassay and gain an understanding of the approaches used. Though several detailed examples have been discussed, the list is by no means exhaustive as can be seen from the many systems that have been briefly mentioned. It will be seen in Chapter 7 that only a few systems have stood the test of time and have gained acceptance as methods that can be applied to routine analytical situations.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N667 – PubChem