Day: November 21, 2022

Morounke, Saibu G. published the artcileGene expression modulation of apoptotic and oestrogen receptor alpha genes by active fractions of selected nigerian plants on cervical cancer cell line (HeLa), Synthetic Route of 192820-78-3, the publication is Tropical Journal of Natural Product Research (2021), 5(4), 772-777, database is CAplus.

The roles of natural product in drug discovery and development cannot be over emphasized. It plays a vital role in human therapy and gives a better understanding on the cellular pathways.This study investigated the modulatory effects of partially purified fractions of Piper guineense Schumach. & Thonn. (Piperaceae), Zanthoxylum zanthoxyloides Lam. (Rutaceae), Amaranthus viridis L. (Amaranthaceae), Costus afer Ker-Gawl. (Zingiberaceae) and Catharanthus roseus (L.) G. Don. (Apocynaceae) on estrogen receptor-α (ESR-α), tumor protein p53 (TP-53), retinoblastoma (RB) and NAD(P) H quinine oxidoreductase (NQO1) genes in cervical cancer cell line (HeLa cells). n-Hexane, ethylacetate, chloroform, and water fractions of 80% ethanol extracts of study plants were screened with brine shrimp lethality and water-soluble tetrazolium-1 (WST-1) cytotoxicity assay. HeLa cells were treated with 1:10 dilutions of IC₅₀ concentrations of test fractions for 24 h, total RNA was extracted, RNA quality was checked, and normalized to a baseline concentration Gene expression were monitored by semi-quant. reverse transcription-polymerase chain reaction (RT-PCR). Results showed that ESR-α was downregulated (p < 0.05) by P. guineense-hexane, C. roseus- chloroform and A. viridis-ethylacetate fractions. TP53 gene was up-regulated (p < 0.05) by P. guineense-hexane and Z. zanthoxyloides-ethylacetate fractions. None of the test fractions caused an up-regulation in the expression of retinoblastoma gene. NQO1 gene was down-regulated (p < 0.05) by C. roseus-chloroform, P. guineense-hexane, A. viridis, C. afer, and Z. zanthoxyloides ethylacetate fractions. Our study provides scientific evidence of the possible anti-proliferative potentials of C. roseus-chloroform, P. guineense-hexane, ethylacetate fractions of A. viridis, C.afer, and Z. zanthoxyloides in cervical cancer.

Tropical Journal of Natural Product Research published new progress about 192820-78-3. 192820-78-3 belongs to indole-building-block, auxiliary class Fused/Partially Saturated Cycles,Dihydroindoles, name is 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, and the molecular formula is C18H16N2O6, Synthetic Route of 192820-78-3.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Roller, Devin G. published the artcileSynthetic Lethal Screening with Small-Molecule Inhibitors Provides a Pathway to Rational Combination Therapies for Melanoma, Computed Properties of 330161-87-0, the publication is Molecular Cancer Therapeutics (2012), 11(11), 2505-2515, database is CAplus and MEDLINE.

Recent data show that extracellular signals are transmitted through a network of proteins rather than hierarchical signaling pathways, suggesting that the inhibition of a single component of a canonical pathway is insufficient for the treatment of cancer. The biol. outcome of signaling through a network is inherently more robust and resistant to inhibition of a single network component. In this study, we conducted a functional chem. genetic screen to identify novel interactions between signaling inhibitors that would not be predicted on the basis of our current understanding of signaling networks. We screened over 300 drug combinations in nine melanoma cell lines and have identified pairs of compounds that show synergistic cytotoxicity. The synergistic cytotoxicities identified did not correlate with the known RAS and BRAF mutational status of the melanoma cell lines. Among the most robust results was synergy between sorafenib, a multikinase inhibitor with activity against RAF, and diclofenac, a nonsteroidal anti-inflammatory drug (NSAID). Drug substitution experiments using the NSAIDs celecoxib and ibuprofen or the MAP-ERK kinase inhibitor PD325901 and the RAF inhibitor RAF265 suggest that inhibition of COX and mitogen-activated protein kinase signaling are targets for the synergistic cytotoxicity of sorafenib and diclofenac. Cotreatment with sorafenib and diclofenac interrupts a pos. feedback signaling loop involving extracellular signal-regulated kinase, cellular phospholipase A2, and COX. Genome-wide expression profiling shows synergy-specific downregulation of survival-related genes. This study has uncovered novel functional drug combinations and suggests that the underlying signaling networks that control responses to targeted agents can vary substantially, depending on unexplored components of the cell genotype. Mol Cancer Ther; 11(11); 2505-15. ©2012 AACR.

Molecular Cancer Therapeutics published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Computed Properties of 330161-87-0.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Alcaraz, Marie-Lyne published the artcileEfficient Syntheses of AZD4407 via Thioether Formation by Nucleophilic Attack of Organometallic Species on Sulphur, Formula: C9H8ClNO3S, the publication is Organic Process Research & Development (2005), 9(5), 555-569, database is CAplus.

The development of two efficient strategies for the synthesis of AZD4407 (I) is reported, both of which are considered suitable for large-scale manufacture In the first approach, 3-bromothiophene is coupled with (2S)-2-methyltetrahydropyran-4-one using Grignard chem. Following hydroxyl protection and lithiation at thiophene C-2, reaction with a protected 5-mercapto-1-methyl-1,3-dihydro-indol-2-one derivative bearing a leaving group on sulfur provides AZD4407 after acid-catalyzed deprotection and epimerization. The second approach starts from 2,4-dibromothiophene, which undergoes a selective Grignard exchange reaction at C-2 followed by reaction with similar protected mercapto-oxindole derivatives Reprotection of the oxindole ring, followed by a second Grignard exchange, and reaction with (2S)-2-methyltetrahydropyran-4-one provides AZD4407 after acid-catalyzed deprotection and epimerization.

Organic Process Research & Development published new progress about 166883-20-1. 166883-20-1 belongs to indole-building-block, auxiliary class Indoline,Chloride,Sulfonyl chlorides,Amide, name is 1-Methyl-2-oxoindoline-5-sulfonyl chloride, and the molecular formula is C9H8ClNO3S, Formula: C9H8ClNO3S.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Narayana, B. published the artcileSimple syntheses of 5-fluoro/ chloro/ bromoindole-2-methanols and 5-fluoro/ chloro/ bromoindole-2-aldehydes, Quality Control of 220943-23-7, the publication is Organic Chemistry: An Indian Journal (2006), 2(1-3), 5-9, database is CAplus.

Efficient and simple methods for the syntheses of 5-haloindole-2-methanols and 5-haloindole-2-aldehydes have been described. 5-Haloindole-2-methanols were prepared by reduction of Me 5-haloindole-2-carboxylates with sodium borohydride in methanol/ THF media and 5-haloindole-2-aldehydes were prepared from the prepared 5-haloindole-2-methanols by oxidation with pyridinium chlorochromate or chromium trioxide-pyridine prepared in situ. The synthesized compounds were isolated in good yields and characterized by ¹H NMR, ¹³C NMR, FABMS and elemental anal.

Organic Chemistry: An Indian Journal published new progress about 220943-23-7. 220943-23-7 belongs to indole-building-block, auxiliary class Indole,Fluoride,Aldehyde, name is 5-Fluoro-1H-indole-2-carbaldehyde, and the molecular formula is C9H6FNO, Quality Control of 220943-23-7.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Tani, Masanobu published the artcileNew strategy for indole synthesis from ethyl pyrrole-2-carboxylate (synthetic studies on indoles and related compounds. XXXIX), COA of Formula: C12H13NO3, the publication is Chemical & Pharmaceutical Bulletin (1996), 44(1), 55-61, database is CAplus.

As a synthetic application of the previously reported C₄-acylation of Et pyrrole-2-carboxylate, a new strategy for indole synthesis was developed. Et pyrrole-2-carboxylate was allowed to react with succinic anhydride or 3-methoxycarbonylpropionyl chloride to give, in good yield, a C₄-succinyl derivative, which was converted into Et 7-oxo-4,5,6,7-tetrahydroindole-2-carboxylate (I) as a key intermediate for indole synthesis. Starting from I, several indoles functionalized on the benzene moiety were synthesized.

Chemical & Pharmaceutical Bulletin published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C9H10O4, COA of Formula: C12H13NO3.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Wu, Fan published the artcileOxyamination of Unactivated Alkenes with Electron-Rich Amines and Acids via a Catalytic Triiodide Intermediate, Name: tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, the publication is Organic Letters (2020), 22(3), 884-890, database is CAplus and MEDLINE.

An aerobic catalytic oxidation process is described for the olefin oxyamination using acids and primary amines as the sources of O and N. Our mechanistic findings point to the formation of triiodide as a critical catalytic intermediate to account for the tolerance of electron-rich nucleophiles. This dual iodide and copper catalytic system is suitable for a formal [5+1] annulation process to access valuable lactam structures and highlighted by the synthesis of the pharmaceutical Zamifenacin.

Organic Letters published new progress about 167015-84-1. 167015-84-1 belongs to indole-building-block, auxiliary class Indols, name is tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, and the molecular formula is C15H20N2O2, Name: tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Mondal, Pravat published the artcileEnantioselective Total Synthesis of Desbromoarborescidines A-C and the Formal Synthesis of (S)-Deplancheine, Recommanded Product: tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, the publication is Journal of Organic Chemistry (2013), 78(13), 6802-6808, database is CAplus and MEDLINE.

Starting from Boc-protected tryptamine and (S)-tetrahydro-5-oxo-2-furancarboxylic acid, facile enantioselective total synthesis of desbromoarborescidines A-C and the formal synthesis of (S)-deplancheine have been accomplished via a common intermediate (S)-indolo[2,3-a]quinolizine (I). Synthesis of enantiomerically pure (S)-acetoxyglutarimide (II), stereoselective reductive intramol. cyclization, hydroxyl group-assisted in situ N-Boc-deprotection, selective deoxygenation of the xanthate ester, and lactam hydrolysis followed by an appropriate exchange of nitrogen regioselectivity in intramol. cyclization were the decisive steps.

Journal of Organic Chemistry published new progress about 167015-84-1. 167015-84-1 belongs to indole-building-block, auxiliary class Indols, name is tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, and the molecular formula is C15H20N2O2, Recommanded Product: tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Di Nicolantonio, Federica published the artcileReplacement of normal with mutant alleles in the genome of normal human cells unveils mutation-specific drug responses, SDS of cas: 2854-32-2, the publication is Proceedings of the National Academy of Sciences of the United States of America (2008), 105(52), 20864-20869, database is CAplus and MEDLINE.

Mutations in oncogenes and tumor suppressor genes are responsible for tumorigenesis and represent favored therapeutic targets in oncol. The authors exploited homologous recombination to knock-in individual cancer mutations in the genome of nontransformed human cells. Sequential introduction of multiple mutations was also achieved, demonstrating the potential of this strategy to construct tumor progression models. Knock-in cells displayed allele-specific activation of signaling pathways and mutation-specific phenotypes different from those obtainable by ectopic oncogene expression. Profiling of a library of pharmacol. agents on the mutated cells showed striking sensitivity or resistance phenotypes to pathway-targeted drugs, often matching those of tumor cells carrying equivalent cancer mutations. Thus, knock-in of single or multiple cancer alleles provides a pharmacogenomic platform for the rational design of targeted therapies.

Proceedings of the National Academy of Sciences of the United States of America published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C23H23ClN2O4, SDS of cas: 2854-32-2.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Khomula, Eugen V. published the artcilein vitro nociceptor neuroplasticity associated with in vivo opioid-induced hyperalgesia, HPLC of Formula: 330161-87-0, the publication is Journal of Neuroscience (2019), 39(36), 7061-7073, database is CAplus and MEDLINE.

Opioid-induced hyperalgesia (OIH) is a serious adverse event produced by opioid analgesics. Lack of an in-vitro model has hindered study of its underlying mechanisms. Recent evidence has implicated a role of nociceptors in OIH. To investigate the cellular and mol. mechanisms of OIH in nociceptors, in vitro, s.c. administration of an analgesic dose of fentanyl (30μg/kg, s.c.) was performed in vivo in male rats. Two days later, when fentanyl was administered intradermally (1μg, i.d.), in the vicinity of peripheral nociceptor terminals, it produced mech. hyperalgesia (OIH). Addnl., 2 d after systemic fentanyl, rats had also developed hyperalgesic priming (opioid-primed rats), long-lasting nociceptor neuroplasticity manifested as prolongation of prostaglandin E2 (PGE2) hyperalgesia. OIH was reversed, in vivo, by intrathecal administration of cordycepin, a protein translation inhibitor that reverses priming. When fentanyl (0.5 nm) was applied to dorsal root ganglion (DRG) neurons, cultured from opioid-primed rats, it induced a μ-opioid receptor (MOR)-dependent increase in [Ca²⁺]i in 26% of small-diameter neurons and significantly sensitized (decreased action potential rheobase) weakly IB4⁺ and IB4^– neurons. This sensitizing effect of fentanyl was reversed in weakly IB4⁺ DRG neurons cultured from opioid-primed rats after in vivo treatment with cordycepin, to reverse of OIH. Thus, in vivo administration of fentanyl induces nociceptor neuroplasticity, which persists in culture, providing evidence for the role of nociceptor MOR-mediated calcium signaling and peripheral protein translation, in the weakly IB4-binding population of nociceptors, in OIH.

Journal of Neuroscience published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, HPLC of Formula: 330161-87-0.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Khomula, Eugen V. published the artcileOpioid-induced hyperalgesic priming in single nociceptors, HPLC of Formula: 330161-87-0, the publication is Journal of Neuroscience (2021), 41(1), 31-46, database is CAplus and MEDLINE.

Clin. μ-opioid receptor (MOR) agonists produce hyperalgesic priming, a form of maladaptive nociceptor neuroplasticity, resulting in pain chronification. We have established an in vitro model of opioid-induced hyperalgesic priming (OIHP), in male rats, to identify nociceptor populations involved and its maintenance mechanisms. OIHP was induced in vivo by systemic administration of fentanyl and confirmed by prolongation of prostaglandin E2 (PGE2) hyperalgesia. Intrathecal cordycepin, which reverses Type I priming, or the combination of Src and mitogen-activated protein kinase (MAPK) inhibitors, which reverses Type II priming, both partially attenuated OIHP. Parallel in vitro experiments were performed on small-diameter (<30μm) dorsal root ganglion (DRG) neurons, cultured from fentanyl-primed rats, and rats with OIHP treated with agents that reverse Type I or Type II priming. Enhancement of the sensitizing effect of a low concentration of PGE2 (10 nm), another characteristic feature of priming, measured as reduction in action potential (AP) rheobase, was found in weakly isolectin B4 (IB4)-pos. and IB4-neg. (IB4-) neurons. In strongly IB4-pos. (IB4+) neurons, only the response to a higher concentration of PGE2 (100 nm) was enhanced. The sensitizing effect of 10 nm PGE2 was attenuated in weakly IB4+ and IB4- neurons cultured from rats whose OIHP was reversed in vivo. Thus, in vivo administration of fentanyl induces neuroplasticity in weakly IB4+ and IB4- nociceptors that persists in vitro and has properties of Type I and Type II priming. The mechanism underlying the enhanced sensitizing effect of 100 nm PGE2 in strongly IB4+ nociceptors, not attenuated by inhibitors of Type I and Type II priming, remains to be elucidated.

Journal of Neuroscience published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, HPLC of Formula: 330161-87-0.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles