Month: November 2022

Roeglin, Lars published the artcileDNA and RNA-controlled switching of protein kinase activity, Recommanded Product: 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, the publication is ChemBioChem (2009), 10(4), 758-765, database is CAplus and MEDLINE.

Protein switches use the binding energy gained upon recognition of ligands to modulate the conformation and binding properties of protein segments. We explored whether the programmable nucleic acid mediated recognition might be used to design or mimic constraints that limit the conformational freedom of peptide segments. The aim was to design nucleic acid-peptide conjugates in which the peptide portion of the conjugate would change the affinity for a protein target upon hybridization. This approach was used to control the affinity of a PNA-phosphopeptide conjugate for the signal transduction protein Src kinase, which binds the cognate phosphopeptides in a linear conformation. Peptide-nucleic acid arms were attached to known peptide binders. The chimeric mols. were studied in three modes: (1) as single strands, (2) constrained by intermol. hybridization (duplex formation) and (3) constrained by intramol. hybridization (hairpin formation). Of note, duplexes that were designed to accommodate bulged peptide structures (for example, in hairpins or bulges) had lower binding affinities than duplexes in which the peptide was allowed to adopt a more relaxed conformation. Greater than 90-fold differences in binding affinities were observed It was, thus, feasible to make use of DNA hybridization to reversibly switch from no to almost complete inhibition of Src-SH2-peptide binding, and vice versa. A series of DNA and PNA-based hybridization experiments revealed the importance of charges and conformational effects. Nucleic acid mediated switching was extended to the use of RNA; this enabled a regulation of the enzymic activity of the Src kinase. The proof-of-principle results demonstrate for the first time that PNA-peptide chimeras can transduce changes of the concentration of a given RNA mol. to changes of the activity of a signal transduction enzyme.

ChemBioChem 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 C40H35N7O8, Recommanded Product: 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.

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

Abutayeh, Reem F. published the artcileDesign and Synthesis of New Sulfonamides-Based Flt3 Inhibitors, Computed Properties of 1453-82-3, the publication is Medicinal Chemistry (Sharjah, United Arab Emirates) (2020), 16(3), 403-412, database is CAplus and MEDLINE.

Background: Flt3 is an oncogenic kinase involved in different leukemias. It is most prominently associated with acute myeloid leukemia (AML). Flt3-specific inhibitors have shown promising results in interfering with AML. Methods: The crystallog. structures of two inhibitors complexed within Flt3, namely, quizartinib and F6M, were used to guide the synthesis of new sulfonamide-based Flt3 inhibitors. Results: One of the prepared compounds showed low micromolar anti-Flt3 bioactivity, and interestingly, low micromolar bioactivity against the related oncogenic kinase VEGFR2. Conclusion: Sulfonamides were successfully used as privileged scaffolds for the synthesis of novel Flt3 inhibitors of micromolar potencies.

Medicinal Chemistry (Sharjah, United Arab Emirates) published new progress about 1453-82-3. 1453-82-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is Isonicotinamide, and the molecular formula is C6H6N2O, Computed Properties of 1453-82-3.

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

Rai, Sunil K. published the artcileSalts and Cocrystal of Etodolac: Advantage of Solubility, Dissolution, and Permeability, Related Products of amides-buliding-blocks, the publication is Crystal Growth & Design (2020), 20(7), 4512-4522, database is CAplus.

Etodolac (ETD) is a nonsteroidal anti-inflammatory drug (NSAID) approved by the United States Food and Drug Administration (US-FDA) in 1991 for the treatment of rheumatoid arthritis. Because of its poor aqueous solubility and high permeability, ETD falls under Biopharmaceutics Classification System (BCS) Class II drug. The present study was aimed to screen stable salts and cocrystals of ETD using Generally Recognized as Safe (GRAS) and a few non-GRAS coformers. Crystallization of five salts (i.e., isopropylamine = isoPA, n-hexylamine = nHA, cyclohexylamine = cycloHA, 2-phenylethylamine = phEA, piperazine = PPZ) and one cocrystal (isonicotinamide = INT) was successful. These products were characterized by single crystal X-ray and powder diffraction. Differential scanning calorimetry (DSC) showed a single endotherm for the salts, which confirmed their thermal stability and phase homogeneity, except for ETD^–·phEA⁺ where a solid-solid transition at 152°C was observed with an enthalpy of transition ΔH ≈ 16 J/g. Among the five salts, ETD^–·isoPA⁺ showed the highest solubility of 267.50 mg/mL and ~20 times faster intrinsic dissolution rate than ETD in pH 7.0 phosphate buffer medium. The salts are stable under solubility and dissolution conditions as confirmed by fitting the powder X-ray diffraction profile of each sample after the experiment with the calculated lines from the X-ray structure. Permeability and flux anal. of ETD salts showed that ETD^–·isoPA⁺ exhibits a high flux rate across the semipermeable membrane due to a higher mol. mobility and greater concentration gradient. Solid form screening of the nonsteroidal anti-inflammatory drug Etodolac afforded five salts with isopropylamine, n-hexylamine, cyclohexylamine, 2-phenylethylamine, and piperazine and one cocrystal with isonicotinamide. The isopropylamine salt showed the highest solubility at 267.50 mg/mL, which exhibited ~20 times faster intrinsic dissolution rate than etodolac in pH 7.0 phosphate buffer. Thus, short chain (low lipophilic) amines are preferred over long chain (high lipophilic) aliphatic amines to improve the solubility, dissolution, and physicochem. properties of acidic drugs.

Crystal Growth & Design published new progress about 1453-82-3. 1453-82-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is Isonicotinamide, and the molecular formula is C6H6N2O, Related Products of amides-buliding-blocks.

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

Wiktelius, Daniel published the artcileIn Situ Assembly of Choline Acetyltransferase Ligands by a Hydrothiolation Reaction Reveals Key Determinants for Inhibitor Design, Related Products of amides-buliding-blocks, the publication is Angewandte Chemie, International Edition (2021), 60(2), 813-819, database is CAplus and MEDLINE.

The potential drug target choline acetyltransferase (ChAT) catalyzes the production of the neurotransmitter acetylcholine in cholinergic neurons, T-cells, and B-cells. Herein, we show that arylvinylpyridiniums (AVPs), the most widely studied class of ChAT inhibitors, act as substrate in an unusual CoA-dependent hydrothiolation reaction. This in situ synthesis yields an adduct that is the actual enzyme inhibitor. The adduct is deeply buried in the active site tunnel of ChAT and interactions with a hydrophobic pocket near the choline binding site have major implications for the mol. recognition of inhibitors. Our findings clarify the inhibition mechanism of AVPs, establish a drug modality that exploits a target-catalyzed reaction between exogenous and endogenous precursors, and provide new directions for the development of ChAT inhibitors with improved potency and bioactivity.

Angewandte Chemie, International Edition 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 C6H8BNO3, Related Products of amides-buliding-blocks.

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

Liman, Recep published the artcileGenotoxic and cytotoxic effects of pethoxamid herbicide on Allium cepa cells and its molecular docking studies to unravel genotoxicity mechanism, Safety of 2-Chloroacetamide, the publication is Environmental Science and Pollution Research, database is CAplus and MEDLINE.

Pethoxamid is chloroacetamide herbicide. Pethoxamid is commonly used to kill different weeds in various crops. Pethoxamid can leach in the water and soil and can cause toxic effects to other non-target species. Current study is therefore aimed to perform the investigation of the cytotoxic and genotoxic effects of pethoxamid on Allium cepa cells. The root growth, mitotic index (MI), chromosomal aberrations (CAs), and DNA damage were assessed through root growth inhibition, A. cepa ana-telophase, and alk. comet assays, resp. Furthermore, mol. docking was performed to evaluate binding affinity of pethoxamid on DNA and very-long-chain fatty acid (VLCFA) synthases. In root growth inhibition test, onion root length was statistically significantly decreased in a concentration dependent manner. Concentration- and time-dependent decreases in MI were observed, whereas increase in CAs such as disturbed ana-telophase, chromosome laggards, stickiness, anaphase bridges, and DNA damage was caused by the pethoxamid on A. cepa root cells. Mol. docking revealed that pethoxamid binds selectively to GC-rich regions in the minor groove of the DNA structure and showed remarkable binding affinity against all synthases taking part in the sequential biosynthesis of VLCFAs. It was concluded that the pethoxamid-induced genotoxicity and cytotoxicity may be through multiple binding ability of this herbicide with DNA and VLCFA synthases.

Environmental Science and Pollution Research 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, Safety of 2-Chloroacetamide.

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

Okolo, ChrisTina published the artcileHexafluoroisopropanol-Mediated Domino Reaction for the Synthesis of Thiazolo-androstenones: Potent Anticancer Agents, Application of 3-Methoxybenzothioamide, the publication is ACS Omega (2018), 3(12), 17991-18001, database is CAplus and MEDLINE.

A cascade reaction of thioamides with 6-bromoandrostenedione in hexafluoroisopropanol formed substituted thiazolo-androstenones. This is a simple and mild protocol to synthesize novel mols. by using readily available reagents and substrates. Feasibility of the reaction has been rationalized by d. functional theory (DFT) calculations Moreover, these compounds are potent growth inhibitors of colon, central nervous system (CNS), melanoma, ovarian, and renal cancer cell lines with 50% growth inhibition (GI50) values as low as 1.04 μM.

ACS Omega published new progress about 64559-06-4. 64559-06-4 belongs to amides-buliding-blocks, auxiliary class Amine,Benzene,Amide,Ether, name is 3-Methoxybenzothioamide, and the molecular formula is C8H9NOS, Application of 3-Methoxybenzothioamide.

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

Ullah, Rahim published the artcileThe 7-Hydroxyflavone attenuates chemotherapy-induced neuropathic pain by targeting inflammatory pathway, Computed Properties of 169590-42-5, the publication is International Immunopharmacology (2022), 108674, database is CAplus and MEDLINE.

Vincristine and paclitaxel are widely used chemotherapeutic drugs for the treatment of brain tumors, breast cancer, leukemia, lymphomas, and malignant solid tumors. Though, these drugs are associated with some severe adverse effects including peripheral neuropathic pain. The anti-nociceptive and anti-inflammatory properties of the 7-Hydroxyflavone (7HF) were evaluated in the mice using thermally- and chem.-induced nociception, naloxone antagonistic test, and carrageenan-induced paw edema models. Initially, the in-vitro cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitory assays were carried out. Peripheral neuropathic pain was induced in the Sprague Dawley (SD) rats by administration of paclitaxel (4 mg/kg) and vincristine (200μg/kg) on days 1, 3, 5, 7, and 9, resp. The protective effect of 7HF was assessed against the chemotherapy-induced peripheral neuropathy in the rats. Moreover, the expression of the inflammatory mediators in the spinal cord was investigated through RT-PCR. In addition, a computational study was performed to find the potential therapeutic targets and the binding mechanism of 7HF. The 7HF caused concentration-dependent inhibition of COX-2 and 5-LOX, it attenuated the nociceptive pain, carrageenan-induced paw edema, and the development of mech. and cold allodynia, and hyperalgesia dose-dependently without causing motor coordination deficit. Likewise, the 7HF decreased the vincristine-induced increased expression of different inflammatory mediators including COX-2, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and nuclear factor-kappa B (NF-κB). The computational study showed the effective interactions of 7HF with the binding sites of NF-κB, COX-2, and 5-LOX, exert its inhibitory activities. These findings reveal that the 7HF has anti-nociceptive, anti-inflammatory, and anti-neuropathic potentials.

International Immunopharmacology 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 C9H21NO3, Computed Properties of 169590-42-5.

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

Al-kuraishy, Hayder M. published the artcileThe Prospective Effect of Allopurinol on the Oxidative Stress Index and Endothelial Dysfunction in Covid-19, Synthetic Route of 137862-53-4, the publication is Inflammation (2022), 45(4), 1651-1667, database is CAplus and MEDLINE.

SARS-CoV-2 by the direct cytopathic effect or indirectly through the propagation of pro-inflammatory cytokines could cause endothelial dysfunction (ED) and oxidative stress (OS). It has been reported that OS is triggered by various types of viral infections, including SARS-CoV-2. Into the bargain, allopurinol is regarded as a potent antioxidant that acts through inhibition of xanthine oxidase (XO), which is an essential enzyme of purine metabolism Herein, the present study aimed to find the potential protective effects of allopurinol on the biomarkers of OS and ED in patients with severe Covid-19. This single-center cohort study recruited 39 patients with mild-moderate Covid-19 compared with 41 patients with severe Covid-19. Nineteen patients with severe Covid-19 were on the allopurinol treatment because of underlying chronic gout 3 years ago compared with 22 Covid-19 patients not on this treatment. The recruited patients were allocated into three groups: group I, mild-moderate Covid-19 on the standard therapy (n = 39); group II, severe Covid-19 patients on the standard therapy only (n = 22); and group III, severe Covid-19 patients on the standard therapy plus allopurinol (n = 19). The duration of the study was 3 wk from the time of hospitalization till the time of recovery. In addition, inflammatory biomarkers (D-dimer, LDH, ferritin, CRP, procalcitonin), neutrophil-lymphocyte ratio (NLR), endothelin-1 (ET-1), uric acid and oxidative stress index (OSI), CT scan score, and clin. score were evaluated at the time of admission and discharge regarding the effect of allopurinol treatment adds to the standard treatment of Covid-19. Allopurinol plus standard treatment reduced LDH, ferritin, CRP, procalcitonin, and ET-1 serum level significantly (P < 0.05) compared with Covid-19 patients on standard treatment. Besides, neutrophil (%), lymphocyte (%), and neutrophil-lymphocyte ratio (NLR) were reduced in patients with severe Covid-19 on standard treatment plus allopurinol compared with Covid-19 patients on standard treatment alone (P < 0.01). OSI was higher in patients with severe Covid-19 than mild-moderate Covid-19 patients (P = 0.00001) at admission. At the time of discharge, the oxidative status of Covid-19 patients was significantly improved compared with that at admission (P = 0.01). In conclusion, Covid-19 severity is linked with high OS and inflammatory reaction with ED development. High uric acid in patients with severe Covid-19 is correlated with high OS and inflammatory biomarkers. Allopurinol with standard treatment in patients with severe Covid-19 reduced oxidative and inflammatory disorders with significant amelioration of ED and clin. outcomes.

Inflammation 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 C24H29N5O3, Synthetic Route of 137862-53-4.

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

Shklyaev, V. S. published the artcileSynthesis of enamino amides of the 1,2,3,4-tetrahydroisoquinoline series, COA of Formula: C5H8N2O, the publication is Khimiya Geterotsiklicheskikh Soedinenii (1989), 1239-42, database is CAplus.

Treating 3,4-R¹₂C₆H₃CH₂C(OH)R²R³ [R¹ = MeO, H, R² = MeO, Me, R³ = Me, Et, R²R³ = (CH₂)₄, (CH₂)₅] with NCCH₂CONR⁴R⁵ (R⁴ = H, R⁵ = Me, Et, 2-thiazolyl; R⁴R⁵N = morpholino) in H₂SO₄ gave 57-83% isoquinolines I. Addnl. obtained were the biisoquinolines II (n = 4, 6, 7) and the corresponding piperazine derivative

Khimiya Geterotsiklicheskikh Soedinenii published new progress about 15029-36-4. 15029-36-4 belongs to amides-buliding-blocks, auxiliary class Nitrile,Amine,Aliphatic hydrocarbon chain,Amide, name is 2-Cyano-N-ethylacetamide, and the molecular formula is C12H16O3, COA of Formula: C5H8N2O.

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

Abul, Mai published the artcilePrenatal Activation of Glucocorticoid Receptors Induces Memory Impairment in a Sex-Dependent Manner: Role of Cyclooxygenase-2, Application In Synthesis of 169590-42-5, the publication is Molecular Neurobiology (2022), 59(6), 3767-3777, database is CAplus and MEDLINE.

Prenatal exposure to dexamethasone (DEX) results in long-lasting effects on cognitive functions such as learning and memory impairment. However, the mechanisms underlying these DEX-induced deleterious effects are not well known. Here, we assessed whether cyclooxygenase-2 (COX-2) is involved in the impact of prenatal exposure to DEX on learning and memory during adulthood. Pregnant Sprague-Dawley rats received daily injections of either DEX (0.2 mg/kg; i.p.) or saline from gestation day (GD) 14 until GD21. Gene and protein expression of COX-2, as well as presynaptic (synaptophysin) and postsynaptic (postsynaptic d. protein-95) proteins, were monitored in the dorsal and ventral hippocampi of adult male and female offspring. A different cohort of adult male and female rat offspring was given daily injections of either vehicle or a specific COX-2 inhibitor (celecoxib 10 mg/kg, i.p.) for 5 consecutive days and was subsequently subjected to Morris water maze memory test. Prenatal DEX enhanced the expression of COX-2 protein and cox-2 mRNA in the dorsal hippocampus of adult female but not male rats. This enhanced COX-2 expression was associated with reduced expression in pre- and postsynaptic proteins and altered memory acquisition and retention. Administration of COX-2-specific inhibitor alleviated prenatal DEX-induced memory impairment in adult female rats. This study suggests that prenatal activation of glucocorticoid receptors stimulates COX-2 gene and protein expression and impairs hippocampal-dependent spatial memory in female but not male rat offspring. Furthermore, COX-2 selective inhibitors can be used to alleviate the long-lasting deleterious effects of corticosteroid medication during pregnancy.

Molecular Neurobiology 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, Application In Synthesis of 169590-42-5.

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