Month: November 2022

Zhou, Min published the artcileFingerprinting pharmaceuticals of multiple sources at a provincial watershed scale, COA of Formula: C24H29N5O3, the publication is Science of the Total Environment (2022), 153356, database is CAplus and MEDLINE.

Pharmaceutical residues in the aquatic environment have increasingly attracted public concerns but their fingerprint of sources remain unclear at a watershed scale. This study systematically explored pharmaceutical residues in effluent of 8 different type of sources in a provincial watershed in China using a multi-category protocol of pharmaceutical quantification. Seventy-seven out of 94 target compounds from 6 categories were quantified in effluent, up to 71,318 ng L^-1 in total from urban hospital sources with 20 antibiotics and 32 others. The spectrum of the quantified compounds in effluent significantly differentiated the urban (hospitals, domestic sewages, and WWTPs), rural (health centers and domestic sewages), and agricultural production sources (poultry and swine breeding yards, aquaculture ponds, and paddy fields). Compounds of non-steroidal anti-inflammation drugs (NSAIDs), cardiovascular drugs (CVs), and central nervous drugs (CNs) could fingerprint the three groups of sources. However, the three categories contributed 7 out of 10 compounds with high risk (risk quotient >1.0) to the aquatic environment identified by the eco-environmental risk assessment. No high-risk compounds were identified in effluent of urban WWTPs. Findings of this study suggest source identification and compound spectrum fingerprinting are crucial for studies on pharmaceutical residues in the aquatic environment, especially the complexity of pharmaceutical residues in source effluents for exploring source-sink dynamics at a watershed scale.

Science of the Total Environment published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C12H10FeO4, COA of Formula: C24H29N5O3.

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

Sawada, Yu published the artcileResolvin E1 attenuates murine psoriatic dermatitis, Category: amides-buliding-blocks, the publication is Scientific Reports (2018), 8(1), 1-9, database is CAplus and MEDLINE.

The potential of omega-3 poly-unsaturated fatty acids (PUFAs) as a therapeutic target for psoriasis, a chronic inflammatory skin disease of IL-23/IL-17 axis, is a long-disputed question, since various epidemiol. studies have suggested the association between high-intake of omega-3 PUFAs and the reduced frequency and severity of psoriasis. However, their actual significance and the mol. mechanisms remain largely unknown. To address these issues, we focused on resolvin E1 (RvE1), an omega-3 PUFAs-derived metabolite, and examined its effects on psoriatic dermatitis, using an imiquimod-induced mouse psoriasis model. RvE1 potently suppressed the inflammatory cell infiltration and epidermal hyperplasia in the psoriatic skin. RvE1 decreased the mRNA expression of IL-23 in the skin. Consistently, RvE1 inhibited IL-23 production by dendritic cells (DCs) in vitro. Furthermore, RvE1 exerted inhibitory effects on migration of cutaneous DCs and γδ T cells, a major IL-17-producing cell population in mouse, both in vivo and in vitro. These suppressive effects of RvE1 were mediated by its antagonistic function on BLT1, a receptor of leukotriene B4, and were also observed in human DCs, Th17 and Tc17 cells. Our results indicate a novel mechanism of omega-3 PUFA-mediated amelioration of psoriasis, and suggest a potential of RvE1 as a therapeutic target for psoriasis.

Scientific Reports 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, Category: amides-buliding-blocks.

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

Westerlund, Kristina published the artcileDesign, Preparation, and Characterization of PNA-Based Hybridization Probes for Affibody-Molecule-Mediated Pretargeting, SDS of cas: 186046-83-3, the publication is Bioconjugate Chemistry (2015), 26(8), 1724-1736, database is CAplus and MEDLINE.

In radioimmunotherapy, the contrast between tumor and normal tissue can be improved by using a pretargeting strategy with a primary targeting agent, which is conjugated to a recognition tag, and a secondary radiolabeled mol. binding specifically to the recognition tag. The secondary mol. is injected after the targeting agent has accumulated in the tumor and is designed to have a favorable biodistribution profile, with fast clearance from blood and low uptake in normal tissues. In this study, we have designed and evaluated two complementary peptide nucleic acid (PNA)-based probes for specific and high-affinity association in vivo. An anti-HER2 Affibody-PNA chimera, Z_HER2:342-SR-HP1, was produced by a semisynthetic approach using sortase A catalyzed ligation of a recombinantly produced Affibody mol. to a PNA-based HP1-probe assembled using solid-phase chem. A complementary HP2 probe carrying a DOTA chelator and a tyrosine for dual radiolabeling was prepared by solid-phase synthesis. CD (CD) spectroscopy and UV thermal melts showed that the probes can hybridize to form a structured duplex with a very high melting temperature (T_m), both in HP1:HP2 and in Z_HER2:342-SR-HP1:HP2 (T_m = 86-88 °C), and the high binding affinity between Z_HER2:342-SR-HP1 and HP2 was confirmed in a surface plasmon resonance (SPR)-based binding study. Following a moderately fast association (1.7 × 10⁵ M^-1 s^-1), the dissociation of the probes was extremely slow and <5% dissociation was observed after 17 h. The equilibrium dissociation constant (K_D) for Z_HER2:342-SR-HP1:HP2 binding to HER2 was estimated by SPR to be 212 pM, suggesting that the conjugation to PNA does not impair Affibody binding to HER2. The biodistribution profiles of ¹¹¹In- and ¹²⁵I-labeled HP2 were measured in NMRI mice, showing very fast blood clearance rates and low accumulation of radioactivity in kidneys and other organs. The measured radioactivity in blood was 0.63 ± 0.15 and 0.41 ± 0.15%ID/g for ¹²⁵I- and ¹¹¹In-HP2, resp., at 1 h p.i., and at 4 h p.i., the kidney accumulation of radioactivity was 0.17 ± 0.04%ID/g for ¹²⁵I-HP2 and 3.83 ± 0.39%ID/g for ¹¹¹In-HP2. Taken together, the results suggest that a PNA-based system has suitable biophys. and in vivo properties and is a promising approach for pretargeting of Affibody mols.

Bioconjugate Chemistry published new progress about 186046-83-3. 186046-83-3 belongs to amides-buliding-blocks, auxiliary class Purine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(2-(((benzhydryloxy)carbonyl)amino)-6-oxo-5H-purin-9(6H)-yl)acetamido)acetic acid, and the molecular formula is C10H10CoF6P, SDS of cas: 186046-83-3.

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

Darguzyte, Milita published the artcileInfluence of Riboflavin Targeting on Tumor Accumulation and Internalization of Peptostar Based Drug Delivery Systems, Product Details of C11H22N2O4, the publication is Bioconjugate Chemistry (2020), 31(12), 2691-2696, database is CAplus and MEDLINE.

Riboflavin carrier protein (RCP) and riboflavin transporters (RFVTs) have been reported to be highly overexpressed in various cancer cells. Hence, targeting RCP and RFVTs using riboflavin may enhance tumor accumulation and internalization of drug delivery systems. To test this hypothesis, butyl-based 3-arm peptostar polymers were synthesized consisting of a lysine core (10 units per arm) and a sarcosine shell (100 units per arm). The end groups of the arms and the core were successfully modified with riboflavin and the Cy5.5 fluorescent dye, resp. While in phosphate buffered saline the functionalized peptostars showed a bimodal behavior and formed supramol. structures over time, they were stable in the serum maintaining their hydrodynamic diameter of 12 nm. Moreover, the polymers were biocompatible and the uptake of riboflavin targeted peptostars in A431 and PC3 cells was higher than in nontargeted controls and could be blocked competitively. In vivo, the polymers showed a moderate passive tumor accumulation, which was not significantly different between targeted and nontargeted peptostars. Nonetheless, at the histol. level, internalization into tumor cells was strongly enhanced for the riboflavin-targeted peptostars. Based on these results, we conclude that passive accumulation is dominating the accumulation of peptostars, while tumor cell internalization is strongly promoted by riboflavin targeting.

Bioconjugate Chemistry published new progress about 2418-95-3. 2418-95-3 belongs to amides-buliding-blocks, auxiliary class Chiral,Carboxylic acid,Amine,Aliphatic hydrocarbon chain,Ester,Amino acide derivatives, name is H-Lys(Boc)-OH, and the molecular formula is C11H22N2O4, Product Details of C11H22N2O4.

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

Lain, Sonia published the artcileDiscovery, in vivo activity, and mechanism of action of a small-molecule p53 activator, HPLC of Formula: 380315-80-0, the publication is Cancer Cell (2008), 13(5), 454-463, database is CAplus and MEDLINE.

We have carried out a cell-based screen aimed at discovering small mols. that activate p53 and have the potential to decrease tumor growth. Here, we describe one of our hit compounds, tenovin-1, along with a more water-soluble analog, tenovin-6. Via a yeast genetic screen, biochem. assays, and target validation studies in mammalian cells, we show that tenovins act through inhibition of the protein-deacetylating activities of SirT1 and SirT2, two important members of the sirtuin family. Tenovins are active on mammalian cells at one-digit micromolar concentrations and decrease tumor growth in vivo as single agents. This underscores the utility of these compounds as biol. tools for the study of sirtuin function as well as their potential therapeutic interest.

Cancer Cell 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, HPLC of Formula: 380315-80-0.

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

Smith, Christine C. published the artcileThe synthesis and application of a diazirine-modified uridine analogue for investigating RNA-protein interactions, COA of Formula: C6H10F3NO, the publication is RSC Advances (2014), 4(89), 48228-48235, database is CAplus.

The roles played by many ncRNAs remain largely unknown. Similarly, relatively little is known about the RNA binding proteins involved in processing ncRNA. Identification of new RNA/RNA binding protein (RBP) interactions may pave the way to gain a better understanding of the complex events occurring within cells during gene expression and ncRNA biogenesis. The development of chem. tools for the isolation of RBPs is of paramount importance. In this context, we report on the synthesis of the uridine phosphoramidite U^Dz that bears a diazirine moiety on the nucleobase. RNA probes containing U^Dz units were irradiated in the presence of single-stranded DNA binding protein (SSB), which is also known to bind ssRNAs, and shown to efficiently (15% yield) and selectively cross-link to the protein. The corresponding diazirine-modified uridine triphosphate U^DzTP was synthesized and its capacity to act as a substrate for the T7 RNA polymerase was tested in transcription assays. U^DzTP was accepted with a maximum yield of 38% for a 26mer RNA containing a single incorporation and 28% yield for triple consecutive incorporations. Thus, this uridine analog represents a convenient biochem. tool for the identification of RNA binding proteins and unraveling the role and function played by ncRNAs.

RSC Advances 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 C7H13ClNNaO5S, COA of Formula: C6H10F3NO.

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

Nagatake, Takahiro published the artcileBLT1 mediates commensal bacteria-dependent innate immune signals to enhance antigen-specific intestinal IgA responses, Synthetic Route of 321673-30-7, the publication is Mucosal Immunology (2019), 12(5), 1082-1091, database is CAplus and MEDLINE.

Leukotriene B₄ receptor 1 (BLT1) triggers the migration of granulocytes and activated T cells; however, its role in B-cell function remains unclear. Here we report that BLT1 is required to induce the production of antigen-specific IgA against oral vaccine through mediating innate immune signals from commensal bacteria. B cells acquire BLT1 expression during their differentiation to IgA⁺ B cells and plasma cells in Peyer’s patches and the small intestinal lamina propria, resp. BLT1 KO mice exhibited impaired production of antigen-specific fecal IgA to oral vaccine despite normal IgG responses to systemically immunized antigen. Expression of MyD88 was decreased in BLT1 KO gut B cells and consequently led to diminished proliferation of commensal bacteria-dependent plasma cells. These results indicate that BLT1 enhances the proliferation of commensal bacteria-dependent IgA⁺ plasma cells through the induction of MyD88 and thereby plays a key role in the production of antigen-specific intestinal IgA.

Mucosal 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, Synthetic Route of 321673-30-7.

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

van Leeuwen, Ingeborg M. M. published the artcileMechanism-specific signatures for small-molecule p53 activators, COA of Formula: C25H34N4O2S, the publication is Cell Cycle (2011), 10(10), 1590-1598, database is CAplus and MEDLINE.

Recent advances in the field of pharmacol. activation of the p53 tumor suppressor are beginning to be translated into the clinic. In addition, small mols. that activate p53 through established mechanisms of action are proving invaluable tools for basic research. Here we analyze and compare the effects of nutlin-3, tenovin-6 and low doses of actinomycin-D on p53 and its main neg. regulator, mdm2. We reveal striking differences in the speed at which these compounds increase p53 protein levels, with nutlin-3 having a substantial impact within minutes. We also show that nutlin-3 is very effective at increasing the synthesis of mdm2 mRNA, mdm2 being not only a modulator of p53 but also a transcriptional target. In addition, we show that nutlin-3 stabilizes mdm2’s conformation and protects mdm2 from degradation These strong effects of nutlin-3 on mdm2 correlate with a remarkable rate of recovery of p53 levels upon removal of the compound We discuss the potential application of our results as mol. signatures to assess the on-target effects of small-mol. mdm2 inhibitors. To conclude, we discuss the implications of our observations for using small-mol. p53 activators to reduce the growth of tumors retaining wild-type p53 or to protect normal tissues against the undesired side effects of conventional chemotherapy.

Cell Cycle 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 C25H47NO8, COA of Formula: C25H34N4O2S.

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

Jagerovic, Nadine published the artcileDiscovery of 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-3-hexyl-1H-1,2,4-triazole, a Novel in Vivo Cannabinoid Antagonist Containing a 1,2,4-Triazole Motif, Computed Properties of 2447-79-2, the publication is Journal of Medicinal Chemistry (2004), 47(11), 2939-2942, database is CAplus and MEDLINE.

A new series of 1,2,4-triazoles have been prepared and the evaluation of their cannabinoid properties have been carried out. The title compound, 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-hexyl-1H-1,2,4-triazole (I) showed cannabinoid silent antagonist activity in mouse vas deferens and guinea pig ileum preparations and in vivo assays (cannabinoid tetrad) in mouse. It did not have intrinsic activity in these bioassays, and therefore, it did not behave as a partial agonist or an inverse agonist. Mol. modeling of I was carried out on Δ⁹-tetrahydrocannabinoic acid B.

Journal of Medicinal Chemistry 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, Computed Properties of 2447-79-2.

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

Garbrecht, William L. published the artcileThe synthesis of certain 5-aminotetrazole derivatives. I. The action of hydrazoic acid on some dialkylcyanamides, Name: N,N-Dibenzylcyanamide, the publication is Journal of Organic Chemistry (1953), 1003-13, database is CAplus.

A number of 5-dialkylaminotetrazoles, HN.N:N.N:C-NR₂ (I), are prepared to be tested for their pharmacol. activity by the interaction of R₂NCN and HN₃ in polar and non-polar solvents. R₂NCN are prepared by 2 methods: (A) 12 cc. Br in 40 cc. Skellysolve B is added dropwise to 32 g. Am₂NH and 59 g. KCN in 60 cc. H₂O with vigorous stirring at 0°, giving 88% Am₂NCN, b₁₂ 154-8°, n²⁰_D 1.4422; (B) 53 g. BrCN in ether is added (2 h.) to 71 g. pyrrolidine in ether with cooling and stirring, giving 58% 1-cyanopyrrolidine, b₁₇ 107-10°, n²³_D 1.4670. Other R₂NCN prepared are: R = Bu, b₃₅ 147-51°, n²⁰_D 1.4382; iso-Bu, b₂₅ 123°, n²⁰_D 1.4346; iso-Am, b₁₄ 134°, n²⁰_D 1.4405; PhCH₂, b₁₀ 145-8°, m. 54°; Me, PhCH₂, b₁₂ 139-42°, n²⁰_D 1.5297; Et, PhCH₂, b₁₂ 160°, n²⁰_D 1.5223; 1-cyanopiperidine, b₁₁ 102°, n²⁵_D 1.4678; 4-cyanomorpholine, b₁₅ 117-19°, n²⁵_D 1.4708. Adding (1.5 h.) 250 cc. concentrated H₂SO₄ to 520 g. NaN₃ in 500 cc. H₂O and 1.5 l. C₆H₆ with stirring and cooling, and drying the C₆H₆ layer with Na₂SO₄ give a stock solution containing 15-17 g. HN₃/100 cc. Adding HN₃ from 33 g. NaN₃ in 100 cc. H₂O to 39 g. Bu₂NCN in 200 cc. 95% EtOH gives 85% I (R = Bu), fine needles, m. 132.5-3.5°. Refluxing 80 g. Me(PhCH₂)NCN in 200 cc. xylene containing 32 g. HN₃ 5 h., adding another 100 cc. HN₃ solution, and refluxing another 18 h. give 89% I (R = Me and PhCH₂), fine needles, m. 135.5-6.5° [HCl salt, needles, decompose 179° (sealed tube)]. Refluxing 10 g. (iso-Am)₂NCN with 35 cc. xylene containing 4.5 g. HN₃ 22 h. and, after addition of another 35 cc., another 67 h. gives 9.8 g. I (R = iso-Am), needles, m. 100-1°. Refluxing 6.3 g. Pr₂NCN and 4.2 g. NH₃ in 100 cc. EtOH and 50 cc. H₂O 65 h. gives 39% I (R = iso-Pr), existing in 2 forms, m. 162.5-3.5° and 184° (decomposition). The following addnl. I are prepared [R, solvent used, time (hrs.), % yield, and m.p. in the order given]: Me (II), aqueous EtOH, 5.5, 78, 235-6°; Et, aqueous EtOH, 6, 43, 124-5°; allyl, aqueous EtOH, 17.5, 36 (EtOAc, 20, 58), 96-7°; Bu, aqueous EtOH, 15, 85, 132.5-3.5° (HCl salt, plates, decompose 183°); iso-Bu, aqueous EtOH, 14, 91, 190-1°; Am, aqueous EtOH, 24, 87, 91.5-2.5°; PhCH₂, aqueous EtOH, 46, 91, 158-9°; Et and PhCH₂, xylene, 57, 88, 134.5-5°; piperidino, aqueous EtOH, 43, 79 (C₆H₆, 25, 85), 199-9.5°; morpholino, C₆H₆, 23, 78, 180.5-1°; 1-pyrrolidinyl, aqueous EtOH, 26, 54 (C₆H₆, 23, 86), 231° (decomposition). The Ag salts are prepared by treating I in EtOH with aqueous AgNO₃ solution The apparent dissociation constants and equivalent weights of I in 50% MeOH were determined and the UV absorption curves of I (R = H), II, and some related compounds are described.

Journal of Organic Chemistry published new progress about 2451-91-4. 2451-91-4 belongs to amides-buliding-blocks, auxiliary class Nitrile,Amine,Benzene, name is N,N-Dibenzylcyanamide, and the molecular formula is C15H14N2, Name: N,N-Dibenzylcyanamide.

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