Month: November 2022

Miek, Laura published the artcileStaphylococcus aureus controls eicosanoid and specialized pro-resolving mediator production via lipoteichoic acid, Computed Properties of 169590-42-5, the publication is Immunology (2022), 166(1), 47-67, database is CAplus and MEDLINE.

Staphylococcus aureus causes severe infections associated with inflammation, such as sepsis or osteomyelitis. Inflammatory processes are regulated by distinct lipid mediators (LMs) but how their biosynthetic pathways are orchestrated in S. aureus infections is elusive. We show that S. aureus strikingly not only modulates pro-inflammatory, but also inflammation-resolving LM pathways in murine osteomyelitis and osteoclasts as well as in human monocyte-derived macrophages (MDMs) with different phenotype. Targeted LM metabololipidomics using ultra-performance liquid chromatog.-tandem mass spectrometry revealed massive generation of LM with distinct LM signature profiles in acute and chronic phases of S. aureus-induced murine osteomyelitis in vivo. In human MDM, S. aureus elevated cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1), but impaired the levels of 15-lipoxygenase-1 (15-LOX-1), with resp. changes in LM signature profiles initiated by these enzymes, i.e., elevated PGE2 and impaired specialized pro-resolving mediators, along with reduced M2-like phenotypic macrophage markers. The cell wall component, lipoteichoic acid (LTA), mimicked the impact of S. aureus elevating COX-2/mPGES-1 expression via NF-κB and p38 MAPK signalling in MDM, while the impairment of 15-LOX-1 correlates with reduced expression of Lamtor1. In conclusion, S. aureus dictates LM pathways via LTA resulting in a shift from anti-inflammatory M2-like towards pro-inflammatory M1-like LM signature profiles.

Immunology published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Computed Properties of 169590-42-5.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Burnett, Marianne E. published the artcileStructural characterization of the aquaporin inhibitor 2-nicotinamido-1,3,4-thiadiazole, Synthetic Route of 51987-99-6, the publication is Acta Crystallographica, Section C: Structural Chemistry (2015), 71(12), 1074-1079, database is CAplus and MEDLINE.

Nicotinamides are a class of compounds with a wide variety of applications, from use as antimicrobial agents to inhibitors of biol. processes. These compounds are also cofactors, which are necessary components of metabolic processes. Structural modification gives rise to the activities observed Similarly, 1,3,4-thiadiazoles have been shown to possess antioxidant, antimicrobial, or anti-inflammatory biol. activity. To take advantage of each of the inherent characteristics of the two aforementioned functional groups, 2-nicotinamido-1,3,4-thiadiazole, C₈H₆N₄OS, was synthesized. Since defining chem. connectivity is paramount in understanding biol. activity, in this report, the structural characterization of 2-nicotinamido-1,3,4-thiadiazole has been carried out using X-ray crystallog. methods. The NMR-derived assignments were made possible by utilizing one- (1D) and two-dimensional (2D) NMR techniques. In addition, UV-Visible and IR spectroscopies, and elemental anal. were used to fully characterize the product synthesized by the one-step reaction between nicotinoyl chloride hydrochloride and 2-amino-1,3,4-thiadiazole. Computational parameters related to blood-brain barrier permeability are also presented.

Acta Crystallographica, Section C: Structural Chemistry published new progress about 51987-99-6. 51987-99-6 belongs to amides-buliding-blocks, auxiliary class Pyridine,Thiadiazole,Amine,Amide,Inhibitor, name is N-(1,3,4-Thiadiazol-2-yl)nicotinamide, and the molecular formula is C8H6N4OS, Synthetic Route of 51987-99-6.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Schultz, David C. published the artcilePyrimidine inhibitors synergize with nucleoside analogues to block SARS-CoV-2, Computed Properties of 169590-42-5, the publication is Nature (London, United Kingdom) (2022), 604(7904), 134-140, database is CAplus and MEDLINE.

The SARS-CoV-2 virus has infected more than 261 million people and has led to more than 5 million deaths in the past year and a half¹ (https://www.who.org/). Individuals with SARS-CoV-2 infection typically develop mild-to-severe flu-like symptoms, whereas infection of a subset of individuals leads to severe-to-fatal clin. outcomes. Although vaccines have been rapidly developed to combat SARS-CoV-2, there has been a dearth of antiviral therapeutics. There is an urgent need for therapeutics, which has been amplified by the emerging threats of variants that may evade vaccines. Large-scale efforts are underway to identify antiviral drugs. Here we screened approx. 18,000 drugs for antiviral activity using live virus infection in human respiratory cells and validated 122 drugs with antiviral activity and selectivity against SARS-CoV-2. Among these candidates are 16 nucleoside analogs, the largest category of clin. used antivirals. This included the antivirals remdesivir and molnupiravir, which have been approved for use in COVID-19. RNA viruses rely on a high supply of nucleoside triphosphates from the host to efficiently replicate, and we identified a panel of host nucleoside biosynthesis inhibitors as antiviral. Moreover, we found that combining pyrimidine biosynthesis inhibitors with antiviral nucleoside analogs synergistically inhibits SARS-CoV-2 infection in vitro and in vivo against emerging strains of SARS-CoV-2, suggesting a clin. path forward.

Nature (London, United Kingdom) published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C4H12ClNO, Computed Properties of 169590-42-5.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Groves, M. J. published the artcilep53 and cell cycle independent dysregulation of autophagy in chronic lymphocytic leukaemia, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is British Journal of Cancer (2013), 109(9), 2434-2444, database is CAplus and MEDLINE.

Background: Activation of wild-type p53 with the small mol. sirtuin inhibitor Tenovin-6 (Tnv-6) induces p53-dependent apoptosis in many malignant cells. In contrast, Tnv-6 reduces chronic lymphocytic leukemia (CLL) cell viability with dysregulation of autophagy, without increasing p53-pathway activity. Methods: Here, we have investigated whether a quiescent phenotype (unique to CLL) determines the Tnv-6 response, by comparing the effects of Tnv-6 on activated and proliferating CLL. We further studied if these responses are p53-dependent. Results: Unlike quiescent cells, cell death in activated cultures treated with Tnv-6 was consistently associated with p53 upregulation. However, p53 acetylation remained unchanged, without caspase-3 cleavage or apoptosis on electron microscopy. Instead, cellular ultrastructure and protein profiles indicated autophagy inhibition, with reduced ubiquitin-proteasome activity. In specimens with mutant TP53 cultured with Tnv-6, changes in the autophagy-associated protein LC3 occurred independently of p53. Cells treated with Tnv-6 analogs lacking sirtuin inhibitory activity had attenuated LC3 lipidation compared with Tnv-6 (P≤0.01), suggesting that autophagy dysregulation occurs predominantly through an effect on sirtuins. Conclusion: These cell cycle and p53-independent anti-leukemic mechanisms potentially offer novel therapeutic approaches to target leukemia-sustaining cells in CLL, including in disease with p53-pathway dysfunction. Whether targets in addition to sirtuins contribute to autophagy dysregulation by Tnv-6, requires further investigation.

British Journal of Cancer published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

de Lipthay, Julia R. published the artcileBacterial diversity and community structure of a sub-surface aquifer exposed to realistic low herbicide concentrations, Synthetic Route of 2447-79-2, the publication is FEMS Microbiology Ecology (2004), 49(1), 59-69, database is CAplus and MEDLINE.

An increasing number of herbicides are found in our groundwater environments. This underlines the need for examining the effects of herbicide exposure on the indigenous groundwater microbial communities, as microbial degradation is the major process responsible for the complete removal of most contaminants. We examined the effect of in situ exposure to realistic low concentrations of herbicides on the microbial diversity and community structure of sub-surface sediments from a shallow aquifer near Vejen (Denmark). Three different community analyses were performed: colony morphol. typing, sole C source utilization in Biolog EcoPlates, and denaturing gradient gel electrophoresis. Cluster anal. demonstrated that the microbial communities of those aquifer sediments that acclimated to the herbicide exposure also had similar community structure. This observation was concurrent for all 3 community analyses. In contrast, no significant effect was found on the bacterial diversity, except for the culturable fraction where a significantly increased richness and Shannon index was found in the herbicide acclimated sediments. The results of this study show that in situ exposure of sub-surface aquifers to realistic low concentrations of herbicides may alter the overall structure of a natural bacterial community, although significant effects on the genetic diversity and C substrate usage cannot be detected. The observed impact was probably due to indirect effects. In future studies, the inclusion of methods that specifically detect relevant microbial sub-populations and functional genes is recommended.

FEMS Microbiology Ecology published new progress about 2447-79-2. 2447-79-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Benzene,Amide, name is 2,4-Dichlorobenzamide, and the molecular formula is C7H5Cl2NO, Synthetic Route of 2447-79-2.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Jiang, Wenhao published the artcilePGE2 activates EP4 in subchondral bone osteoclasts to regulate osteoarthritis, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Bone Research (2022), 10(1), 27, database is CAplus and MEDLINE.

Prostaglandin E2 (PGE2), a major cyclooxygenase-2 (COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis (OA) patients. However, NSAIDs, including COX-2 inhibitors, have severe side effects during OA treatment. Therefore, the identification of novel drug targets of PGE2 signaling in OA progression is urgently needed. Osteoclasts play a critical role in subchondral bone homeostasis and OA-related pain. However, the mechanisms by which PGE2 regulates osteoclast function and subsequently subchondral bone homeostasis are largely unknown. Here, we show that PGE2 acts via EP4 receptors on osteoclasts during the progression of OA and OA-related pain. Our data show that while PGE2 mediates migration and osteoclastogenesis via its EP2 and EP4 receptors, tissue-specific knockout of only the EP4 receptor in osteoclasts (EP4LysM) reduced disease progression and osteophyte formation in a murine model of OA. Furthermore, OA-related pain was alleviated in the EP4LysM mice, with reduced Netrin-1 secretion and CGRP-pos. sensory innervation of the subchondral bone. The expression of platelet-derived growth factor-BB (PDGF-BB) was also lower in the EP4LysM mice, which resulted in reduced type H blood vessel formation in subchondral bone. Importantly, we identified a novel potent EP4 antagonist, HL-43, which showed in vitro and in vivo effects consistent with those observed in the EP4LysM mice. Finally, we showed that the Gαs/PI3K/AKT/MAPK signaling pathway is downstream of EP4 activation via PGE2 in osteoclasts. Together, our data demonstrate that PGE2/EP4 signaling in osteoclasts mediates angiogenesis and sensory neuron innervation in subchondral bone, promoting OA progression and pain, and that inhibition of EP4 with HL-43 has therapeutic potential in OA.

Bone Research published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Liu, Yang published the artcilePyridazinone derivatives displaying highly potent and selective inhibitory activities against c-Met tyrosine kinase, Application In Synthesis of 849833-86-9, the publication is European Journal of Medicinal Chemistry (2016), 322-333, database is CAplus and MEDLINE.

Over activation of c-Met tyrosine kinase is known to promote tumorigenesis and metastasis, as well as therapeutic resistance. Herein the authors describe the design, synthesis and biol. activities of novel, ATP-competitive, c-Met tyrosine kinase inhibitors that are members of the 6-aryl-2-(3-(heteroarylamino)benzyl)pyridazinone family. A structure-activity relationship (SAR) study of these substances led to identification of a pyridazinone derivative as a highly selective and potent c-Met tyrosine inhibitor, which displays favorable pharmacokinetic properties in mice and significant antitumor activity against a c-Met driven EBC-1 tumor xenograft. The synthesis of the target compounds was achieved using [(3-iodophenyl)methyl]-3-pyridazinone derivatives as key intermediates.

European Journal of Medicinal Chemistry published new progress about 849833-86-9. 849833-86-9 belongs to amides-buliding-blocks, auxiliary class Fluoride,Boronic acid and ester,Amine,Benzene,Amide,Boronic Acids,Boronic Acids,Boronic acid and ester, name is (3-Fluoro-4-(methylcarbamoyl)phenyl)boronic acid, and the molecular formula is C8H9BFNO3, Application In Synthesis of 849833-86-9.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Wang, Xuan published the artcilePreparation and evaluation of polyphenol derivatives as potent antifouling agents: addition of a side chain affects the biological activity of polyphenols, Application of 2-Chloroacetamide, the publication is Biofouling (2022), 38(1), 29-41, database is CAplus and MEDLINE.

In this study, eight polyphenol derivatives were prepared to serve as green antifoulants. Polyphenol derivatives, which can hinder the growth of bacteria and algae and decrease the adhesion of some marine organisms, showed good AF activity; in particular, the activities of these derivatives were much higher than those of the corresponding polyphenols. The antibacterial rates of the products (20μg ml-1) exceeded 88%. Moreover, the anti-algal rates of compounds a3, b1, b2, b3 and b4 (15μg ml-1) were over 57% at 240 h, but these compounds showed low toxicity, and the 120 h EC50 values were > 6.60μg ml-1. In addition, there were fewer marine microorganisms on the test panel than on the control. The above results show that some polyphenol derivatives possess relatively high antibacterial, anti-algal, and AF activity; more notably, the addition of chlorine atoms and amide groups can further increase the activity of these derivatives

Biofouling published new progress about 79-07-2. 79-07-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Aliphatic hydrocarbon chain,Amide,Inhibitor, name is 2-Chloroacetamide, and the molecular formula is C7H8BFO2, Application of 2-Chloroacetamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Wang, Xuan published the artcilePerformance assessment of capsaicin derivatives containing amide groups used as active substances for antifouling coatings, Application of 2-Chloroacetamide, the publication is Progress in Organic Coatings (2021), 106515, database is CAplus.

The culprit of biofouling is the formation and reproduction of viable microbial biofilms. For many years, biofouling is a critical issue in marine pollution treatment and has drawn great attention. Herein, eight capsaicin (CAP) derivatives were prepared using aromatic hydrocarbons and amides as raw materials, thereinto, compounds A1, A2, A3, A4, and B1 has not been reported, being considered some new compounds Meanwhile, the antifouling (AF) property of CAP derivatives were characterized for the first time. The inhibition rates of these CAP derivatives (20μg·mL^-1) against Escherichia coli and Staphylococcus aureus exceed 80% and 92%, resp. The anti-algal activity of the CAP derivatives is time and concentration dependent. Compounds A3 and A4 exhibit excellent anti-algal activity (> 77.30% against Nitzschia closterium and > 82.50% against C. vulgaris), and their toxicity is lower than that of currently used antifoulants, such as TBT and SeaNine 211. Most importantly, AF coatings with CAP derivatives show excellent AF effects in marine environments for 180 days; moreover, as auxiliary AF agents, CAP derivatives further enhance the AF performance of cuprous oxide-containing coatings, which are widely used as antifoulants. The phenolic hydroxyl group, benzene ring, amide group and chlorine atom in the CAP derivatives are supposed to be the main active groups contributing to the AF performance. This study may provide a promising method to solve marine pollution.

Progress in Organic Coatings published new progress about 79-07-2. 79-07-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Aliphatic hydrocarbon chain,Amide,Inhibitor, name is 2-Chloroacetamide, and the molecular formula is C6H8O4, Application of 2-Chloroacetamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Ren, Kun published the artcileQuercetin induces the selective uptake of HDL-cholesterol via promoting SR-BI expression and the activation of the PPARγ/LXRα pathway, SDS of cas: 321673-30-7, the publication is Food & Function (2018), 9(1), 624-635, database is CAplus and MEDLINE.

Reverse cholesterol transport (RCT) is the process to deliver cholesterol to the liver for further excretion and involves scavenger receptor class B type I (SR-BI)-mediated selective lipid uptake (SLU) from high-d. lipoprotein cholesterol (HDL-C). The up-regulation of hepatic SR-BI expression accelerates HDL-C clearance in circulation and impedes the development of atherosclerosis (AS). In the present study, we explored the modulation of hepatic SR-BI expression and SR-BI-mediated SLU by quercetin, a natural flavonoid compound in the diet with a favorable role in cardiovascular disorders. We found that quercetin significantly increased the expression level of SR-BI in HepG2 cells in a concentration- and time-dependent manner. Besides, quercetin had stimulatory effects on the binding of 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (Dil)-labeled HDL to hepatocytes and ¹²⁵I/³H-CE-HDL association Treatment with small interfering RNA (siRNA) or SR-BI specific inhibitor, BLT-1, inhibited quercetin-induced Dil-HDL binding and selective HDL-C uptake. Treatment with quercetin increased both proliferator-activated receptor γ (PPARγ) and liver X receptor α (LXRα) levels. Addnl., the quercetin-induced expression of SR-BI, Dil-HDL binding and the selective uptake of HDL-C were significantly attenuated by treatment with PPARγ siRNA, LXRα siRNA, and their antagonists, resp. In C57BL/6 mice, quercetin administration potently increased SR-BI, PPARγ and LXRα levels and lipid accumulation in the liver. Altogether, our results suggest that quercetin-induced up-regulation of SR-BI and subsequent lipid uptake in hepatocytes might contribute to its beneficial effects on cholesterol homeostasis and atherogenesis.

Food & Function published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, SDS of cas: 321673-30-7.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics