Month: December 2022

Ladds, Marcus J. G. W. published the artcileExploitation of dihydroorotate dehydrogenase (DHODH) and p53 activation as therapeutic targets: a case study in polypharmacology, Quality Control of 380315-80-0, the publication is Journal of Biological Chemistry (2020), 295(52), 17935-17949, database is CAplus and MEDLINE.

The tenovins are a frequently studied class of compounds capable of inhibiting sirtuin activity, which is thought to result in increased acetylation and protection of the tumor suppressor p53 from degradation However, as we and other laboratories have shown previously, certain tenovins are also capable of inhibiting autophagic flux, demonstrating the ability of these compounds to engage with more than one target. In this study, we present two addnl. mechanisms by which tenovins are able to activate p53 and kill tumor cells in culture. These mechanisms are the inhibition of a key enzyme of the de novo pyrimidine synthesis pathway, dihydroorotate dehydrogenase (DHODH), and the blockage of uridine transport into cells. These findings hold a 3-fold significance: first, we demonstrate that tenovins, and perhaps other compounds that activate p53, may activate p53 by more than one mechanism; second, that work previously conducted with certain tenovins as SirT1 inhibitors should addnl. be viewed through the lens of DHODH inhibition as this is a major contributor to the mechanism of action of the most widely used tenovins; and finally, that small changes in the structure of a small mol. can lead to a dramatic change in the target profile of the mol. even when the phenotypic readout remains static.

Journal of Biological Chemistry published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C20H23N3O2S, Quality Control of 380315-80-0.

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

Ladds, Marcus J. G. W. published the artcileExploitation of dihydroorotate dehydrogenase (DHODH) and p53 activation as therapeutic targets: a case study in polypharmacology, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Journal of Biological Chemistry (2020), 295(52), 17935-17949, database is CAplus and MEDLINE.

The tenovins are a frequently studied class of compounds capable of inhibiting sirtuin activity, which is thought to result in increased acetylation and protection of the tumor suppressor p53 from degradation However, as we and other laboratories have shown previously, certain tenovins are also capable of inhibiting autophagic flux, demonstrating the ability of these compounds to engage with more than one target. In this study, we present two addnl. mechanisms by which tenovins are able to activate p53 and kill tumor cells in culture. These mechanisms are the inhibition of a key enzyme of the de novo pyrimidine synthesis pathway, dihydroorotate dehydrogenase (DHODH), and the blockage of uridine transport into cells. These findings hold a 3-fold significance: first, we demonstrate that tenovins, and perhaps other compounds that activate p53, may activate p53 by more than one mechanism; second, that work previously conducted with certain tenovins as SirT1 inhibitors should addnl. be viewed through the lens of DHODH inhibition as this is a major contributor to the mechanism of action of the most widely used tenovins; and finally, that small changes in the structure of a small mol. can lead to a dramatic change in the target profile of the mol. even when the phenotypic readout remains static.

Journal of Biological Chemistry 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

Sud’enkov, Yu. Ya. published the artcileReaction of poly- and perfluoroalkyl perfluoroisopropyl ketones with secondary amines, Quality Control of 360-92-9, the publication is Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1978), 477-9, database is CAplus.

RCOCF(CF₃)₂ [I; R = CF₃, HCF₂CF₂, H(CF₂)₄] reacted with morpholine at 60° to give 63.3-76.1% RCOX (X = morpholino) and (CF₃)₂CFH. I (R = CF₃, HCF₂) reacted analogously with Et₂NH, I (R = HCF₂CF₂) gave 24.0-47.9% HCF₂CF₂COX (X = NEt₂, NHEt) and 9.4% HCF₂CF₂CH(OH)CF(CF₃)₂ and I [R = H(CF₂)₄] gave 38.1% H(CF₂)₄CONHEt and 35.1% H(CF₂)₄CH(OH)CF(CF₃)₂. HCF₂CF₂COX (X = NEt₂, NHEt) were also prepared from (HCF₂CF₂CO)₂O and the amines.

Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya published new progress about 360-92-9. 360-92-9 belongs to amides-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Amine,Aliphatic hydrocarbon chain,Amide, name is N,N-Diethyl-2,2,2-trifluoroacetamide, and the molecular formula is C20H28BNO5, Quality Control of 360-92-9.

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

Brodeur, Julie C. published the artcileThe problem with implementing fish farms in agricultural regions: A trial in a Pampean pond highlights potential risks to both human and fish health, Synthetic Route of 79-07-2, the publication is Chemosphere (2021), 128408, database is CAplus and MEDLINE.

The safety of creating fish farms in agricultural settings was evaluated by growing Piaractus mesopotamicus in a pond, while crops where cultivated in a nearby field under a pesticide application regime typical of the Pampa region. Atrazine, glyphosate, and its metabolite aminomethylphosphonic acid (AMPA) were detected in the water of the pond at concentrations ranging 92-118μg/L for atrazine, 12-221μg/L for glyphosate, and 21-117μg/L for AMPA. Atrazine and malathion were detected in fish muscles at concentrations ranging 70-105μg/kg for atrazine and 8.6-23.7μg/kg for malathion. Compared to fish raised in a pisciculture, fish from the agricultural pond presented reduced values of pack cell volume, Hb, mean corpuscular Hb and mean corpuscular Hb concentration, together with significantly greater cholinesterase activity in both plasma and liver and reduced glutathione-S-transferase activity in the liver. A comet assay also demonstrated that P. mesopotamicus from the agricultural pond presented a significantly greater level of DNA damage in both erythrocytes and gill cells. Overall, the present study demonstrates that pisciculture ponds established in an agricultural setting may receive pesticides applied to nearby cultures and that these pesticides may be taken up by the fish and affect their physiol. and health. The accumulation of pesticide residues in fish flesh may also present a risk to human consumers and should be closely controlled.

Chemosphere 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 C2H4ClNO, Synthetic Route of 79-07-2.

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

Pandey, Jyotsna published the artcileComplexation of silver(I) with morpholinylthiocarbonic acid amide and its use as an amperometric reagent for trace determination of silver(I), Application In Synthesis of 14294-10-1, the publication is Journal of the Indian Chemical Society (1987), 64(10), 649-51, database is CAplus.

The IR spectrum of the complex formed between Ag(I) and (4-morpholinyl)thiocarbonic acid amide (I) was examined The determination of trace amounts of Ag by amperometric titration at pH 2.86 with I was studied. The min. amount of Ag that could be determined was 0.05 mg/10 mL; the error and standard deviation were <±0.9 and <±0.1%, resp. Diverse ion effect was studied.

Journal of the Indian Chemical Society published new progress about 14294-10-1. 14294-10-1 belongs to amides-buliding-blocks, auxiliary class Morpholine,Thiourea,Amine,Amide, name is Morpholine-4-carbothioamide, and the molecular formula is C5H10N2OS, Application In Synthesis of 14294-10-1.

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

Li, Shasha published the artcileMerging Late-Stage Diversification with Solid-Phase Peptide Synthesis Enabled by High-Throughput On-Resin Reaction Screening, Application of (6-Acetamidopyridin-3-yl)boronic acid, the publication is ACS Catalysis (2022), 12(5), 3201-3210, database is CAplus.

An integrated workflow is described that combines micromole-scale high-throughput experimentation (HTE) reaction screening and solid-phase peptide synthesis (SPPS) to enable rapid synthetic method development for on-resin peptide diversification. Using this new approach, we have identified several sets of robust Suzuki-Miyaura coupling conditions with complementary scope that collectively display broad coverage with respect to both resin-bound peptide substrates containing aryl halide side chains and (hetero)arylboronic acid coupling partners. We have also demonstrated the utility of this integrated SPPS/chem. diversification method by synthesizing a multidimensional library of diverse peptides in high yields.

ACS Catalysis published new progress about 947533-21-3. 947533-21-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Boronic acid and ester,Amine,Amide,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is (6-Acetamidopyridin-3-yl)boronic acid, and the molecular formula is C7H9BN2O3, Application of (6-Acetamidopyridin-3-yl)boronic acid.

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

Pazos, Michael A. published the artcileDistinct Cellular Sources of Hepoxilin A₃ and Leukotriene B₄ Are Used To Coordinate Bacterial-Induced Neutrophil Transepithelial Migration, Safety of [(2-Hexylcyclopentylidene)amino]thiourea, the publication is Journal of Immunology (2015), 194(3), 1304-1315, database is CAplus and MEDLINE.

Neutrophilic infiltration is a leading contributor to pathol. in a number of pulmonary disease states, including cystic fibrosis. Hepoxilin A₃ (HXA₃) is a chemotactic eicosanoid shown to mediate the transepithelial passage of neutrophils in response to infection in several model systems and at multiple mucosal surfaces. Another well-known eicosanoid mediating general neutrophil chemotaxis is leukotriene B₄ (LTB₄). We sought to distinguish the roles of each eicosanoid in the context of infection of lung epithelial monolayers by Pseudomonas aeruginosa. Using human and mouse in vitro transwell model systems, we used a combination of biosynthetic inhibitors, receptor antagonists, as well as mutant sources of neutrophils to assess the contribution of each chemoattractant in driving neutrophil transepithelial migration. We found that following chemotaxis to epithelial-derived HXA₃ signals, neutrophil-derived LTB₄ is required to amplify the magnitude of neutrophil migration. LTB₄ signaling is not required for migration to HXA₃ signals, but LTB₄ generation by migrated neutrophils plays a significant role in augmenting the initial HXA₃-mediated migration. We conclude that HXA₃ and LTB₄ serve independent roles to collectively coordinate an effective neutrophilic transepithelial migratory response.

Journal of Immunology 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, Safety of [(2-Hexylcyclopentylidene)amino]thiourea.

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

McCarthy, Anna R. published the artcileSynthesis and biological characterisation of sirtuin inhibitors based on the tenovins, Application of N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is Bioorganic & Medicinal Chemistry (2012), 20(5), 1779-1793, database is CAplus and MEDLINE.

The tenovins are small mol. inhibitors of the NAD⁺-dependent family of protein deacetylases known as the sirtuins. There remains considerable interest in inhibitors of this enzyme family due to possible applications in both cancer and neurodegenerative disease therapy. Through the synthesis of novel tenovin analogs, further insights into the structural requirements for activity against the sirtuins in vitro are provided. In addition, the activity of one of the analogs in cells led to an improved understanding of the function of SirT1 in cells.

Bioorganic & Medicinal Chemistry published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C20H23N3O2S, Application of N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide.

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

McCarthy, Anna R. published the artcileSynthesis and biological characterisation of sirtuin inhibitors based on the tenovins, Safety of 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Bioorganic & Medicinal Chemistry (2012), 20(5), 1779-1793, database is CAplus and MEDLINE.

The tenovins are small mol. inhibitors of the NAD⁺-dependent family of protein deacetylases known as the sirtuins. There remains considerable interest in inhibitors of this enzyme family due to possible applications in both cancer and neurodegenerative disease therapy. Through the synthesis of novel tenovin analogs, further insights into the structural requirements for activity against the sirtuins in vitro are provided. In addition, the activity of one of the analogs in cells led to an improved understanding of the function of SirT1 in cells.

Bioorganic & Medicinal Chemistry 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, Safety of 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

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

Ghitman, Jana published the artcileMacrophage-targeted mannose-decorated PLGA-vegetable oil hybrid nanoparticles loaded with anti-inflammatory agents, SDS of cas: 169590-42-5, the publication is Colloids and Surfaces, B: Biointerfaces (2022), 112423, database is CAplus and MEDLINE.

This work pledge to extend the therapeutic windows of hybrid nanoparticulate systems by engineering mannose-decorated hybrid nanoparticles based on poly lactic-co-glycolic acid (PLGA) and vegetable oil for efficient delivery of two lipophilic anti-inflammatory therapeutics (Celecoxib-CL and Indomethacin-IMC) to macrophages. The mannose surface modification of nanoparticles is achieved via O-palmitoyl-mannose spacer during the emulsification and nanoparticles assembly process. The impact of targeting motif on the hydrodynamic features (RH, PdI), stability (ζ-potential), drug encapsulation efficiency (DEE) is thoroughly investigated. Besides, the in vitro biocompatibility (MTT, LDH) and susceptibility of mannose-decorated formulations to macrophage as well their immunomodulatory activity (ELISA) are also evaluated. The monomodal distributed mannose-decorated nanoparticles are in the range of nanometric size (RH < 115 nm) with PdI < 0.20 and good encapsulation efficiency (DEE = 46.15% for CL and 76.20% for IMC). The quant. investigation of macrophage uptake shows a 2-fold increase in fluorescence (RFU) of cells treated with mannose-decorated formulations as compared to non-decorated ones (p < 0.001) suggesting an enhanced cell uptake resp. improved macrophage targeting while the results of ELISA experiments suggest the potential immunomodulatory properties of the designed mannose-decorated hybrid formulations.

Colloids and Surfaces, B: Biointerfaces 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, SDS of cas: 169590-42-5.

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