- Adamantane acid esters with alkoxyaryl alcohols: Synthesis, antiproliferative activity, and influence on microtubule network of tumor cells
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Adamantaneacetic and adamantanecarboxylic acid esters containing 3-hydroxy-4-methoxybenzyl, 3,4,5-trimethoxybenzyl, or 5-(hydroxymethyl)-2-methoxyphenyl groups were synthesized as unusual analogs of natural antitumor and anti-tubulin agents combretastatin A-4 and 2-methoxyestradiol. The compounds were found to possess noticeable cytotoxicity to epithelial human carcinoma cell line A549 (EC50 = 4.3—81 μmol L–1). An ability to cause complete depolymerization of microtubule network of A549 cells was demonstrated for 5-(hydroxymethyl)-2-methoxyphenyl adamantan-1-ylacetate (6a) at a concentration of 100 μmol L–1. Ester 6a belongs to a new structural type, which is unusual for the ligands of the tubulin colchicine domain, and is an interesting lead compound for further structural optimization.
- Zefirov,Nurieva,Pikulina, Yu. A.,Ogon′kov,Wobith,Kuznetsov,Zefirova
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- Visible light photocatalytic reduction of aldehydes by Rh(iii)-H: A detailed mechanistic study
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The chemoselective photoreduction of aldehydes in the presence of ketones was achieved using triethanolamine (TEOA) as sacrificial electron donor, proflavine (PF) as photocatalyst and [CpRh(iii)(bpy)Cl]Cl (Rhcat) as mediator. The reducing agent, which reacts with the carbonyl group was found to be [CpRh(iii)(bpy)H]Cl (Rh(iii)-H). Contrary to formate-based reduction, its slow photochemical in situ generation enables to kinetically distinguish aldehydes from ketones. The inherent reactivity difference of the carbonyl compounds is transferred by the method into synthetically useful reaction selectivities. The substrate scope is broad with excellent yields. A detailed study of the reaction mechanism reveals that the photoreduction of the PF triplet and the subsequent reduction of the Rhcat leading to Rh(iii)-H represents the major reaction pathway, which is highly oxygen sensitive. The oxidative quenching of the PF singlet state by Rhcat is a competing mechanism, which prevails in non-degassed systems.
- Ghosh,Slanina,K?nig
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- A Michael initiated - condensation - elimination sequence for the stereoselective synthesis of maleate derivatives
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The paper describes a convenient method for the diastereoselective synthesis of trisubstituted alkenes through the lithium amide mediated union of ketones and diethyl maleate. The reaction has been shown to proceed via a Michael initiated - condensation - elimination (MICE) sequence.
- Harrowven, David C.,Poon, Hon Suen
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- Diethyl Lithiomaleate: Preparation and Use in Synthesis.
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The paper describes a simple method for the generation and alkylation of diethyl lithiomaleate.These reactions proceed with complete retention of alkene geometry, providing a convenient method for the diastereoselective introduction of this useful four carbon synthon.
- Harrowven, David C.,Poon, Hon Suen
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- Controlled reduction of activated primary and secondary amides into aldehydes with diisobutylaluminum hydride
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A practical method is disclosed for the reduction of activated primary and secondary amides into aldehydes using diisobutylaluminum hydride (DIBAL-H) in toluene. A wide range of aryl and alkyl N-Boc, N,N-diBoc and N-tosyl amides were converted into the corresponding aldehydes in good to excellent yields. Reduction susceptible functional groups such as nitro, cyano, alkene and alkyne groups were found to be stable. Broad substrate scope, functional group compatibility and quick conversions are the salient features of this methodology.
- Azeez, Sadaf,Kandasamy, Jeyakumar,Sabiah, Shahulhameed,Sureshbabu, Popuri
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supporting information
p. 2048 - 2053
(2022/03/31)
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- Iron-catalyzed chemoselective hydride transfer reactions
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A Diaminocyclopentadienone iron tricarbonyl complex has been applied in chemoselective hydrogen transfer reductions. This bifunctional iron complex demonstrated a broad applicability in mild conditions in various reactions, such as reduction of aldehydes over ketones, reductive alkylation of various functionalized amines with functionalized aldehydes and reduction of α,β-unsaturated ketones into the corresponding saturated ketones. A broad range of functionalized substrates has been isolated in excellent yields with this practical procedure.
- Coufourier, Sébastien,Ndiaye, Daouda,Gaillard, Quentin Gaignard,Bettoni, Léo,Joly, Nicolas,Mbaye, Mbaye Diagne,Poater, Albert,Gaillard, Sylvain,Renaud, Jean-Luc
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supporting information
(2021/06/07)
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- Identification of Pyruvate Carboxylase as the Cellular Target of Natural Bibenzyls with Potent Anticancer Activity against Hepatocellular Carcinoma via Metabolic Reprogramming
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Cancer cell proliferation in some organs often depends on conversion of pyruvate to oxaloacetate via pyruvate carboxylase (PC) for replenishing the tricarboxylic acid cycle to support biomass production. In this study, PC was identified as the cellular target of erianin using the photoaffinity labeling-click chemistry-based probe strategy. Erianin potently inhibited the enzymatic activity of PC, which mediated the anticancer effect of erianin in human hepatocellular carcinoma (HCC). Erianin modulated cancer-related gene expression and induced changes in metabolic intermediates. Moreover, erianin promotes mitochondrial oxidative stress and inhibits glycolysis, leading to insufficient energy required for cell proliferation. Analysis of 14 natural analogs of erianin showed that some compounds exhibited potent inhibitory effects on PC. These results suggest that PC is a cellular target of erianin and reveal the unrecognized function of PC in HCC tumorigenesis; erianin along with its analogs warrants further development as a novel therapeutic strategy for the treatment of HCC.
- Chen, Yuwen,Huang, Yulan,Jiao, Wei,Li, Fu,Li, Suiyan,Li, Wenhua,Lin, Yuan,Liu, Wanli,Ma, Yuling,Sheng, Yuwen,Suksamrarn, Apichart,Wang, Fei,Wang, Jing,Wei, Xiao,Wisanwattana, Wisanee,Wu, Wenbi,Zeng, Zhongqiu,Zhang, Guolin,Zhang, Jichao,Zhu, Qiyu
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- Synthesis method of selenium-containing isochroman compound
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The invention discloses a synthesis method of a selenium-containing isochroman compound. The synthesis method comprises the following steps: under the protection of nitrogen, adding N-phenylseleno saccharin (NPSSac) into a reactor, then adding dichloromethane to completely dissolve the N-phenylseleno saccharin, adding a 1-[(cinnamoxy) methyl]-3, 4, 5-trimethoxy benzene compound and boron trifluoride diethyl etherate after the N-phenylseleno saccharin is completely dissolved, stirring at 20-60 DEG C for 2-6 hours until the reaction is complete, and after the reaction is finished, quenching, extracting, combining organic phases, drying, concentrating, separating and purifying to obtain the selenium-containing isochroman compound. The synthesis method disclosed by the invention is relatively easy to operate, mild in reaction condition, relatively high in yield, environment-friendly and suitable for large-scale industrial production.
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Paragraph 0046; 0052
(2021/05/29)
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- Synthesis method of 2-benzoxepin compound
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The invention discloses a synthesis method of a 2-benzoxepin compound. The method comprises the following specific steps: under the protection of nitrogen, adding N-phenylseleno-phthalimide into a reactor, then adding anhydrous dichloromethane to dissolve the N-phenylseleno-phthalimide, then adding a 1-[(cinnamyl) methyl]-3, 4, 5-trimethoxybenzene compound, taking zinc chloride as a catalyst, reacting at room temperature, adding saturated sodium bicarbonate for quenching after the reaction is finished, extracting by dichloromethane, combining organic phases, drying by anhydrous magnesium sulfate, concentrating under reduced pressure, and performing silica gel rapid chromatographic purification by thin-layer chromatography silica gel to obtain the 2-benzoxepin compound. The method is simple in reaction operation, mild in reaction condition, relatively high in yield, environment-friendly and suitable for large-scale industrialized production.
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Paragraph 0045; 0050
(2021/05/29)
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- Synthesis method of isochroman compound
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The invention discloses a synthesis method of an isochroman compound, which comprises the following steps of adding dichloromethane and phosphorus tribromide into 3, 4, 5-trimethoxy benzyl alcohol, and reacting to obtain 1-bromomethyl-3, 4, 5-trimethoxy benzene, adding tetrahydrofuran, cinnamyl alcohol, sodium hydride and 1-bromomethyl-3, 4, 5-trimethoxybenzene into a reactor, and reacting to obtain 1-[(cinnamyl oxy)methyl]-3, 4, 5-trimethoxybenzene, adding cyanuric acid into a reactor containing a potassium hydroxide aqueous solution to react, dropwise adding a silver nitrate aqueous solution, and reacting to obtain silver isocyanurate, adding silver isocyanurate, phenyl selenium bromide and anhydrous dichloromethane into a reactor, and reacting to obtain N, N, N-triphenyl seleno isocyanurate, reacting N, N, N-triphenyl seleno isocyanurate, dichloromethane, boron trifluoride diethyl etherate and a 1-[(cinnamyl oxy)methyl]-3, 4, 5-trimethoxybenzene compound to obtain a target product. The method is simple in reaction operation, mild in reaction condition, relatively high in yield and environment-friendly.
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Paragraph 0046; 0051; 0060; 0065; 0073; 0078
(2021/05/15)
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- An asymmetric Salamo-based Zn complex supported on Fe3O4MNPs: a novel heterogeneous nanocatalyst for the silyl protection and deprotection of alcohols under mild conditions
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In this study, a magnetic asymmetric Salamo-based Zn complex (H2L = salen type di-Schiff bases)-supported on the surface of modified Fe3O4(Fe3O4@H2L-Zn) as a new catalyst was designed and characterizedvianumerous analytical techniques such as FT-IR spectroscopy, XRD, EDS, ICP-AES, SEM, TEM, TGA and VSM. An efficient and sustainable synthetic protocol has been presented for the synthesis of silyl ether substructuresviathe silyl protection of alcohols under mild conditions. The synthetic protocol involves a two-component solvent-free reaction between various hydroxyl-bearing substrates and hexamethyldisilazane (HMDS) as an inexpensive silylating agent using Fe3O4@H2L-Zn MNPs as a magnetically separable, recyclable and reusable heterogeneous catalyst. Fe3O4@H2L-Zn MNPs were also applied for the removal of silyl protecting groups from hydroxyl functions using water in CH2Cl2under green conditions. The catalyst demonstrated good to excellent catalytic yield efficiency for both the reactions compared to the commercial metal-based catalysts under green conditions for a wide range of substrates.
- Yao, Hongyan,Wang, Yongsheng,Razi, Maryam Kargar
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p. 12614 - 12625
(2021/04/14)
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- Cyclopentadienone iron tricarbonyl complexes-catalyzed hydrogen transfer in water
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The development of efficient and low-cost catalytic systems is important for the replacement of robust noble metal complexes. The synthesis and application of a stable, phosphine-free, water-soluble cyclopentadienone iron tricarbonyl complex in the reduction of polarized double bonds in pure water is reported. In the presence of cationic bifunctional iron complexes, a variety of alcohols and amines were prepared in good yields under mild reaction conditions.
- Coufourier, Sébastien,Gaillard, Sylvain,Mbaye, Mbaye Diagne,Ndiaye, Daouda,Renaud, Jean-Luc
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supporting information
(2020/01/28)
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- Synthesis and Cytotoxicity Studies of Stilbene Long-Chain Fatty Acid Conjugates
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A series of 16 conjugates of the tubulin polymerization inhibitor combretastatin A4 (CA-4) and other functionally related stilbene with four 18-carbon fatty acids, namely, stearic, oleic, linoleic, and linolenic acids, have been synthesized in good yields. These new derivatives have been evaluated against the KB-3-1 (human epidermoid carcinoma), NCI-H460 (human lung cancer), HEK293 (human embryonic kidney), and MCF-7 (human breast adenocarcinoma) cell lines for antiproliferative activity, with the exhibited cytotoxic activities comparable with those of CA-4 and colchicine. Compounds 22 and 23, CA-4 conjugates of linoleic and linolenic acids, respectively, were determined to have exhibited the most active in vitro assays, with compound 23 exhibiting very similar activity to the parent compound against the NCI-H460 cell line. Our studies further delineated the structurally required Z-geometry of the stilbene moiety and that conjugation of the less active E-stilbenes with the most active fatty acid had minimal or no improvement in their respective activities.
- Brown, David P.,Chen, Zhe-Sheng,Narayanan, Silpa,Wong, Thomas
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- Catalytic Reductions Without External Hydrogen Gas: Broad Scope Hydrogenations with Tetrahydroxydiboron and a Tertiary Amine
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Facile reduction of aryl halides with a combination of 5% Pd/C, B2(OH)4, and 4-methylmorpholine is reported. Aryl bromides, iodides, and chlorides were efficiently reduced. Aryl dihalides containing two different halogen atoms underwent selective reduction: I over Br and Cl, and Br over Cl. Beyond these, aryl triflates were efficiently reduced. This combination was broadly general, effectuating reductions of benzylic halides and ethers, alkenes, alkynes, aldehydes, and azides, as well as for N-Cbz deprotection. A cyano group was unaffected, but a nitro group and a ketone underwent reduction to a low extent. When B2(OD)4 was used for aryl halide reduction, a significant amount of deuteriation occurred. However, H atom incorporation competed and increased in slower reactions. 4-Methylmorpholine was identified as a possible source of H atoms in this, but a combination of only 4-methylmorpholine and Pd/C did not result in reduction. Hydrogen gas has been observed to form with this reagent combination. Experiments aimed at understanding the chemistry led to the proposal of a plausible mechanism and to the identification of N,N-bis(methyl-d3)pyridin-4-amine (DMAP-d6) and B2(OD)4 as an effective combination for full aromatic deuteriation. (Figure presented.).
- Korvinson, Kirill A.,Akula, Hari K.,Malinchak, Casina T.,Sebastian, Dellamol,Wei, Wei,Khandaker, Tashrique A.,Andrzejewska, Magdalena R.,Zajc, Barbara,Lakshman, Mahesh K.
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supporting information
p. 166 - 176
(2020/01/02)
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- Unusual transformation of 4-hydroxy/methoxybenzylic alcohols via C[sbnd]C ipso-substitution reaction using proton-exchanged montmorillonite as media
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We present here proton-exchanged montmorillonite-mediated an unusual transformation of 4-hydroxy and 4-methoxybenzylic alcohols to form symmetrical benzylic ethers and diarylmethanes under mild conditions. Nuclear magnetic resonance spectroscopy and density functional theory calculations support a plausible mechanism, which includes a distinctive aromatic C[sbnd]C ipso-substitution reaction with a hydroxymethyl group as the C-based leaving group.
- Chen, Dongyin,Chen, Xuan,Dong, Zezhong,Jiang, Nan,Li, Fei,Yun, Yangfang,Zhou, Yu
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supporting information
(2020/11/12)
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- Direct Exploitation of the Ethynyl Moiety in Calcium Carbide Through Sealed Ball Milling
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Ball milling of calcium carbide (CaC2) enables the reaction of its ethynyl moiety with organic electrophiles. This was realized simply by co-milling CaC2 with organic substrates in a sealed jar without the need for an additive or a catalyst. Various ketones including those bearing α-hydrogens were ethynylated in good yields at short reaction times. Aryl halides are also amenable substrates for this protocol as they furnish aryl ethynes through a benzyne intermediate. This method offers a practical and cheap alternative to the established procedures for introducing ethynyl functionalities.
- Hosseini, Abolfazl,Schreiner, Peter R.
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p. 4339 - 4346
(2020/07/04)
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- Fluorinated benzylidene indanone exhibits antiproliferative activity through modulation of microtubule dynamics and antiangiogenic activity
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The application of fluorine in drug design has been understood significantly by the medicinal chemists in recent years. Modulation of tubulin-microtubule dynamics is one of the most effective targets for cancer chemotherapeutics. A logically designed and identified lead compound, fluorinated benzylidene indanone 1 has been extensively evaluated for cancer pharmacology. It occupied colchicine binding pocket acting as microtubule destabilizer and induced a G2/M phase arrest in MCF-7 cells. Compound 1 exerted an antiangiogenic effect in MCF-7 cells by down-regulating Vascular Endothelial Growth Factor (VEGF) and Hypoxia Inducible Factor-α (HIF-α). In in-vivo efficacy in C3H/Jax mice mammary carcinoma model, benzylidene indanone 1 reduced tumour volumes by 48.2%. Further in acute oral toxicity studies compound 1 was well tolerated and safe up to 1000 mg/kg dose in Swiss albino mice. The fluorinated benzylidene indanone 1, a new chemical entity (NCE) can further be optimized for better efficacy against breast adenocarcinoma.1
- Chanda, Debabrata,Fatima, Eram,Fatima, Kaneez,Khan, Feroz,Luqman, Suaib,Negi, Arvind S.,Shanker, Karuna,Shukla, Aparna,Singh, Aastha,Singh, Arjun,Srivastava, Ankita
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- Storing redox equivalent in the phenalenyl backbone towards catalytic multi-electron reduction
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Storing and transferring electrons for multi-electron reduction processes are considered to be the key steps in various important chemical and biological transformations. In this work, we accomplished multi-electron reduction of a carboxylic acid via a hydrosilylation pathway where a redox-active phenalenyl backbone in Co(PLY-O,O)2(THF)2, stores electrons and plays a preponderant role in the entire process. This reduction proceeds by single electron transfer (SET) from the mono-reduced ligand backbone leading to the cleavage of the Si-H bond. Several important intermediates along the catalytic reduction reaction have been isolated and well characterized to prove that the redox equivalent is stored in the form of a C-H bond in the PLY backbone via a ligand dearomatization process. The ligand's extensive participation in storing a hydride equivalent has been conclusively elucidated via a deuterium labelling experiment. This is a rare example where the ligand orchestrates the multielectron reduction process leaving only the metal to maintain the conformational requirements and fine tunes the electronics of the catalyst.
- Bhunia, Mrinal,Sahoo, Sumeet Ranjan,Shaw, Bikash Kumar,Vaidya, Shefali,Pariyar, Anand,Vijaykumar, Gonela,Adhikari, Debashis,Mandal, Swadhin K.
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p. 7433 - 7441
(2019/08/15)
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- Polypyridyl iridium(III) based catalysts for highly chemoselective hydrogenation of aldehydes
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Iridium-catalyzed transfer hydrogenation (TH) of carbonyl compounds using HCOOR (R = H, Na, NH4) as a hydrogen source is a pivotal process as it provides the clean process and is easy to execute. However, the existing highly efficient iridium catalysts work at a narrow pH; thus, does not apply to a wide variety of substrates. Therefore, the development of a new catalyst which works at a broad pH range is essential as it can gain a broader scope of utilization. Here we report highly efficient polypyridyl iridium(III) catalysts, [Ir(tpy)(L)Cl](PF6)2 {where tpy = 2,2′:6′,2′'-Terpyridine, L = phen (1,10-Phenanthroline), Me2phen (4,7-Dimethyl-1,10-phenanthroline), Me4phen (3,4,7,8-Tetramethyl-1,10-phenanthroline), Me2bpy (4,4′-Dimethyl-2–2′-dipyridyl)} for the chemoselective reduction of aldehydes to alcohols in aqueous ethanol and sodium formate as the hydride source. The reaction can be carried out efficiently in broad pH ranges, from pH 6 to 11. These catalysts are air stable, easy to prepare using commercially available starting materials, and are highly applicable for a wide range of substrates, such as electron-rich or deficient (hetero)arenes, halogens, phenols, alkoxy, ketones, esters, carboxylic acids, cyano, and nitro groups. Particularly, acid and hydroxy groups containing aldehydes were reduced successfully in basic and acidic reaction conditions, demonstrating the efficiency of the catalyst in a broad pH range with high conversion rates under microwave irradiation.
- Pandrala, Mallesh,Resendez, Angel,Malhotra, Sanjay V.
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p. 283 - 288
(2019/09/30)
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- Synthesis, Biological Evaluation, and Molecular Docking of Combretastatin and Colchicine Derivatives and their hCE1-Activated Prodrugs as Antiviral Agents
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Recent studies indicate that tubulin can be a host factor for vector-borne flaviviruses like dengue (DENV) and Zika (ZIKV), and inhibitors of tubulin polymerization such as colchicine have been demonstrated to decrease virus replication. However, toxicity limits the application of these compounds. Herein we report prodrugs based on combretastatin and colchicine derivatives that contain an ester cleavage site for human carboxylesterase, a highly abundant enzyme in monocytes and hepatocytes targeted by DENV. Relative to their parent compounds, the cytotoxicity of these prodrugs was reduced by several orders of magnitude. All synthesized prodrugs containing a leucine ester were hydrolyzed by the esterase in vitro. In contrast to previous reports, the phenylglycine esters were not cleaved by human carboxylesterase. The antiviral activity of combretastatin, colchicine, and selected prodrugs against DENV and ZIKV in cell culture was observed at low micromolar and sub-micromolar concentrations. In addition, docking studies were performed to understand the binding mode of the studied compounds to tubulin.
- Richter, Michael,Boldescu, Veaceslav,Graf, Dominik,Streicher, Felix,Dimoglo, Anatoli,Bartenschlager, Ralf,Klein, Christian D.
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p. 469 - 483
(2019/02/01)
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- Prodrug Activation by a Viral Protease: Evaluating Combretastatin Peptide Hybrids to Selectively Target Infected Cells
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Infections with flaviviruses such as dengue virus (DENV) are prevalent throughout tropical regions worldwide. Replication of these viruses depends on tubulin, a host cell factor that can be targeted to obtain broad-spectrum antiviral agents. Targeting of tubulin does, however, require specific measures to avoid toxic side-effects. Herein, we report the synthesis and biological evaluation of combretastatin peptide hybrids that incorporate the cleavage site of the DENV protease to allow activation of the tubulin ligand within infected cells. The prodrug candidates have no effect on tubulin polymerization in vitro and are 20-2000-fold less toxic than combretastatin A-4. Several of the prodrug candidates were cleaved by the DENV protease in vitro with similar efficiency as the natural viral substrates. Selected compounds were studied in DENV and Zika virus replication assays and had antiviral activity at subcytotoxic concentrations.
- Richter, Michael,Leuthold, Mila M.,Graf, Dominik,Bartenschlager, Ralf,Klein, Christian D.
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supporting information
p. 1115 - 1121
(2019/08/20)
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- Mild palladium-catalysed highly efficient hydrogenation of CN, C-NO2, and CO bonds using H2 of 1 atm in H2O
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Here we present the first example of a mild and high-efficiency protocol enabling a process in water using 1 atm of H2 for the efficient and selective hydrogenation of nitriles, nitro compounds, ketones, and aldehydes to yield primary amines and alcohols with satisfactory yields of up to >99%. Several palladium-based nanoparticle catalysts were prepared from K2PdCl4 and ligands, and one of them was found to be the best and most suitable for the hydrogenation of CN, C-NO2, and CO bonds. In addition, the catalyst Pd-NPs can be easily recycled and reused without losing their activity and selectivity. A plausible mechanism for the hydrogenation of a CN bond was also proposed, representing the first example that possesses great potential for sustainable industrial purposes.
- Liu, Yaxu,He, Shaopo,Quan, Ziyi,Cai, Huizhuo,Zhao, Yang,Wang, Bo
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supporting information
p. 830 - 838
(2019/02/27)
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- Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits bladder cancer cell growth via the mitochondrial apoptosis and JNK pathways
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Erianin, a component extracted from the traditional Chinese herbal medicine Dendrobium, has shown significant anti-tumour activity in various cancers but not in bladder cancer. In this study, we assessed the effects of Erianin on bladder cancer growth and elucidated the related mechanisms. First, Erianin was synthesized with high yields, and markedly suppressed EJ and T24 cell proliferation. It induced G2/M-phase arrest in vitro. Furthermore, Erianin triggered apoptosis via caspase cascades activation and the mitochondrial-mediated apoptotic pathway. Bim up-regulation and Bcl-2 down-regulation as the symbol of apoptosis which were found to play the dominant role in the effects of Erianin. We further showed that JNK pathway activation is necessary for the Erianin-mediated anti-proliferation and apoptotic response. Finally, Erianin exhibited anti-tumour activity and induced apoptosis in tumour tissue in vivo. Collectively, these results suggest that Erianin induced cell cycle G2/M-phase arrest and apoptosis via the JNK signalling pathway in bladder cancer, indicating the potential usefulness of Erianin for the therapy of bladder cancer.
- Zhu, Qiyu,Sheng, Yuwen,Li, Wenhua,Wang, Jing,Ma, Yulin,Du, Baowen,Tang, Yaxiong
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- Nickel-catalyzed intelligent reductive transformation of the aldehyde group using hydrogen
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The selective transformation of the aldehyde group (-CHO) in multifunctional oxygenates is a key challenge in the development of sustainable biomass feedstock. Herein, a smart Ni-MFC catalyst was developed from a 2D Ni-based metal-organic framework (MOF), which efficiently promoted the transformation of -CHO in the presence of H2 to a methyl group (-CH3) via the reductive etherification and hydrogenolysis of the C-O ether bond in methanol. Moreover, the catalytic process could be controlled to directionally produce methyl ether (-CH2OR) using the reductive etherification protocol. For the catalytic reduction of vanillin, the Ni-MFC-700 catalyst guaranteed the full conversion of vanillin and 96.5% yield of the desired 2-methoxy-4-methylphenol (MMP), while the Ni-MFC-500 catalyst afforded about 82.7% yield of 4-(methoxymethyl)-2-methoxyphenol in methanol solvent. This is a novel and promising approach for the valorization of multifunctional oxygenates and biomass-derived platform compounds.
- Tong, Xinli,Guo, Pengfei,Liao, Shengyun,Xue, Song,Zhang, Haigang
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supporting information
p. 5828 - 5840
(2019/11/11)
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- General and Phosphine-Free Cobalt-Catalyzed Hydrogenation of Esters to Alcohols
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Catalytic hydrogenation of esters is essential for the sustainable production of alcohols in organic synthesis and chemical industry. Herein, we describe the first non-noble metal catalytic system that enables an efficient hydrogenation of non-activated esters to alcohols in the absence of phosphine ligands (with a maximum turnover number of 2391). The general applicability of this protocol was demonstrated by the high-yielding hydrogenation of 39 ester substrates including aromatic/aliphatic esters, lactones, polyesters and various pharmaceutical molecules.
- Shao, Zhihui,Zhong, Rui,Ferraccioli, Raffaella,Li, Yibiao,Liu, Qiang
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supporting information
p. 1125 - 1130
(2019/10/22)
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- Combretastatin A4 analogue containing cyanoethylene joining chain and application in preparing antitumor drugs
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The invention a Combretastatin A4 analogue containing a cyanoethylene joining chain and an application in preparing antitumor drugs, which relates to the field of a medicinal compound. A structural formula (I-IV) is shown as the specification, an anticancer candidate compound which has strong inhibitory activity against cancer cells and is not toxic to normal cells is currently lacked, for the reason, the method prepares 19 I-IV series compounds, and the para and meta positions of the B ring (benzene ring) introduce various alkyl groups, alkoxy groups or amino substituents or replace the B ring (benzene ring) with various heterocyclic rings. In the I-series compound, when the para position of the B ring (benzene ring) is substituted with an ethyl group, an isopropyl group, a dimethylaminogroup or a diethylamino group, the proliferation resistance of the cancer cells is very strong, and toxicity is weak for the L-02 normal cells, a selective anticancer activity coefficient (an IC50 value ratio of L-02 normal cells to cancer cells) can even exceed 10,000, and the four compounds have the potential to be developed into safe and highly effective anticancer drugs.
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- Nickel boride mediated chemoselective deprotection of 1,1-diacetates to aldehydes and deprotection with concomitant reduction to alcohols at ambient temperature
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A variety of 1,1-diacetates have been chemoselectively and efficiently deprotected to the corresponding aldehydes as well as deprotected and concomitantly reduced to the corresponding alcohols in high yields at ambient temperature with nickel boride generated in situ using different molar ratios of sodium borohydride and nickel (II) chloride in methanol at room temperature. Deprotection and reduction of a variety of aromatic, aliphatic and heterocyclic acylals have been achieved efficiently. Mild reaction conditions, easy work-up, high yields and chemoselectivity demonstrate the efficiency of this new method.
- Bartwal, Gaurav,Saroha, Mohit,Khurana, Jitender.M.
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- Synthesis and pharmacological evaluation of 2,3-diphenyl acrylonitriles-bearing halogen as selective anticancer agents
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Eighteen novel 2,3-diphenyl acrylonitrile derivatives bearing halogens were designed, synthesized, and evaluated for biological activity. Preliminary in vitro results indicated that the majority of the compounds with a para-substituted halogen had considerable antiproliferative activity against five human cancer cell lines, including MGC-803, AGS, and BEL-7402, with IC50 values in the range of 0.46–100?μm. No significant toxic effects on the non-cancerous human liver cell line L-02 were observed. The selective inhibitory activities against cancer cells were significantly better than that of the control lead compound CA-4 and CA-4P. Particularly, potent activities were found for the derivatives of 3-(4-halogen phenyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile, such as 5c (4-fluoro), 5f (4-bromo), 5h (4-chloro), and 5k (4-trifluoro- methyl), for AGS with IC50 values of 0.75?±?0.24, 0.68?±?0.21, 0.41?±?0.05, and 1.49?±?0.92?μm, respectively. The antiproliferative effects of 5f were attributed to cell-cycle arrest in the G2/M phase, induction of cellular apoptosis, suppression of cell migration, and inhibition of cell colony formation in AGS cells.
- Li, Jia-Jun,Ma, Jun,Xin, Ya-Bing,Quan, Zhe-Shan,Tian, Yu-Shun
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p. 1419 - 1428
(2018/06/06)
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- Anti-acute myeloid leukemia activity of 2-chloro-3-alkyl-1,4-naphthoquinone derivatives through inducing mtDNA damage and GSH depletion
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2-Chloro-3-alkyl-1,4-naphthoquinone derivatives were synthesized and tested as the anti-acute myeloid leukaemia agents. The compound 9b (2-chloro-3-ethyl-5,6,7-trimethoxy-1,4-naphthoquinone) was the most potent toward HL-60 leukaemia cells. In mechanistic study for 9b, the protein levels of mtDNA-specific DNA polymerase γ (poly-γ) and mtDNA transcription factor A (mt-TFA) were decreased after the 24 h treatment, showing the occurrence of mtDNA damage. And 9b triggered cell cycle arrest at S phase accompanied by a secondary block in G2/M phase which had a direct link to the process of mtDNA damage. The dissipations of mitochondrial membrane potential and ATP also proceeded. On the other hand, 9b promoted the generation of ROS and resulted in the oxidation of intracellular GSH to GSSG. This process was coupled to the formation of adduct between 9b and GSH, detected by the UV–Vis spectrum and HRMS analysis. Depletion of GSH by buthionine sulfoximine enhanced ROS level and produced higher cytotoxicity, suggesting GSH was involved in the anti-leukemic mechanism of 9b. Together, our results provide new insights on the molecular mechanism of the derivatives of 2-chloro-1,4-naphthoquinone and 9b might be useful for the further development into an anti-leukemia agent.
- Li, Kun,Yang, Kun,Zheng, Lifang,Li, Yuanyuan,Wang, Qi,Lin, Ruili,He, Dian
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p. 4191 - 4200
(2018/07/21)
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- Novel indole and triazole based hybrid molecules exhibit potent anti-adipogenic and antidyslipidemic activity by activating Wnt3a/β-catenin pathway
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Obesity and dyslipidemia is the two facet of metabolic syndrome, which needs further attention. Recent studies indicate triazole and indole derivatives have remarkable anti-obesity/antidyslipidemic activity. To harness the above-mentioned potential, a series of novel triazole clubbed indole derivatives were prepared using click chemistry and evaluated for anti-adipogenic activity. Based on the structure-activity relationship, essential functional groups which potentiate anti-adipogenic activity were identified. The lead compound 13m exhibited potent anti-adipogenic activity compared to its parent compounds with the IC-50 value of 1.67 μM. Further evaluation of anti-adipogenic activity was conducted in different cell lines such as C3H10T1/2 and hMSC with positive result. The anti-adipogenic effect of compound 13m was most prominent in the early phase of adipogenesis, which is driven by the G1 to S phase cell cycle arrest during mitotic clonal expansion. The mechanistic study suggests that compound 13m exhibit anti-adipogenic property by activating Wnt3a/β-catenin pathway, a known suppressor of key adipogenic genes PPARγ and C/EBPα. It is noteworthy that the compound 13m also reduced serum triglyceride, LDL and total cholesterol in Syrian Golden hamster model of dyslipidemia. The anti-adipogenic activity of compound 13m can also be correlated with decreased expression of PPARγ and increased expression of β-catenin in epididymal white adipose tissue (eWAT) in vivo. The compound 13m also increased the expression of genes involved in reverse cholesterol transport (RCT) such as PPARα and LXR1α indicating another mechanism by which compound 13m ameliorates dyslipidemia in Syrian Golden hamster model. Overall this study provides a unique perspective into the anti-adipogenic/antidyslipidemic property of triazole and indole hybrids molecules with further scope to increase the anti-adipogenic potency for therapeutic intervention of obesity and metabolic syndrome.
- Rajan, Sujith,Puri, Surendra,Kumar, Durgesh,Babu, Madala Hari,Shankar, Kripa,Varshney, Salil,Srivastava, Ankita,Gupta, Abhishek,Reddy, M. Sridhar,Gaikwad, Anil N.
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p. 1345 - 1360
(2017/11/20)
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- Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry
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The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best APN inhibition with an IC50 value of 0.089 ± 0.007 μM, which was two orders of magnitude lower than that of bestatin (IC50 = 9.4 ± 0.5 μM). Compound 13v also showed dose-dependent anti-angiogenesis activities. Even at the lower concentration (10 μM), compound 13v presented similar anti-angiogenesis activity compared with bestatin at 100 μM in both the human umbilical vein endothelial cells (HUVECs) capillary tube formation assay and the rat thoracic aorta rings test. Moreover, compared with bestatin, 13v exhibited comparable, if not better in vivo anti-metastasis activity in a mouse H22 pulmonary metastasis model.
- Cao, Jiangying,Ma, Chunhua,Zang, Jie,Gao, Shuai,Gao, Qianwen,Kong, Xiujie,Yan, Yugang,Liang, Xuewu,Ding, Qin'ge,Zhao, Chunlong,Wang, Binghe,Xu, Wenfang,Zhang, Yingjie
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p. 3145 - 3157
(2018/06/01)
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- Pt(IV) prodrugs containing microtubule inhibitors displayed potent antitumor activity and ability to overcome cisplatin resistance
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It is well-known that cisplatin exhibited a broad spectrum of anticancer activities against many solid tumors, but its severe toxicity and drug resistance have largely limited wider clinical applications. Various strategies have been tried to discover new Pt (II) drugs with at least equal activity as well as low toxicity compared to cisplatin, but the inherent problem remains unsolved. Here we report that Pt (IV) complexes comprising a CA-4 analogue, as dual-targeting Pt (IV) prodrug, were synthesized and evaluated for anti-proliferative activity using MTT assay. Among them, complex 19 displayed most potent activity against the tested cancer cell lines, and simultaneously exhibited better cell selectivity between cancer cells and normal cells than that of cisplatin. Mechanism studies revealed that complex 19 effectively induced cell cycle arrest at the G2/M phase and dramatically disrupted the microtubule organization. Moreover, complex 19 significantly induced cell apoptosis and decreased MMP. Importantly, complex 19 significantly inhibited tumor growth in SK-OV-3 xenograft model in vivo without apparent toxicity.
- Li, Lingxue,Huang, Xiaochao,Huang, Rizhen,Gou, Shaohua,Wang, Zhimei,Wang, Hengshan
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supporting information
p. 666 - 679
(2018/07/29)
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- Sea Urchin Embryo Model As a Reliable in Vivo Phenotypic Screen to Characterize Selective Antimitotic Molecules. Comparative evaluation of Combretapyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles as Tubulin-Binding Agents
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A series of both novel and reported combretastatin analogues, including diarylpyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles, were synthesized via improved protocols to evaluate their antimitotic antitubulin activity using in vivo sea urchin embryo assay and a panel of human cancer cells. A systematic comparative structure-activity relationship studies of these compounds were conducted. Pyrazoles 1i and 1p, isoxazole 3a, and triazole 7b were found to be the most potent antimitotics across all tested compounds causing cleavage alteration of the sea urchin embryo at 1, 0.25, 1, and 0.5 nM, respectively. These agents exhibited comparable cytotoxicity against human cancer cells. Structure-activity relationship studies revealed that compounds substituted with 3,4,5-trimethoxyphenyl ring A and 4-methoxyphenyl ring B displayed the highest activity. 3-Hydroxy group in the ring B was essential for the antiproliferative activity in the diarylisoxazole series, whereas it was not required for potency of diarylpyrazoles. Isoxazoles 3 with 3,4,5-trimethoxy-substituted ring A and 3-hydroxy-4-methoxy-substituted ring B were more active than the respective pyrazoles 1. Of the azoles substituted with the same set of other aryl pharmacophores, diarylpyrazoles 1, 4,5-diarylisoxazoles 3, and 4,5-diaryl-1,2,3-triazoles 7 displayed similar strongest antimitotic antitubulin effect followed by 3,4-diarylisoxazoles 5, 1,5-diaryl-1,2,3-triazoles 8, and pyrroles 10 that showed the lowest activity. Introduction of the amino group into the heterocyclic core decreased the antimitotic antitubulin effect of pyrazoles, triazoles, and to a lesser degree of 4,5-diarylisoxazoles, whereas potency of the respective 3,4-diarylisoxazoles was increased.
- Semenova, Marina N.,Demchuk, Dmitry V.,Tsyganov, Dmitry V.,Chernysheva, Natalia B.,Samet, Alexander V.,Silyanova, Eugenia A.,Kislyi, Victor P.,Maksimenko, Anna S.,Varakutin, Alexander E.,Konyushkin, Leonid D.,Raihstat, Mikhail M.,Kiselyov, Alex S.,Semenov, Victor V.
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p. 700 - 721
(2019/01/03)
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- Preparation and uses of combretastatin A4 analogs containing cyano and halogen
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The present invention provides preparation and uses of combretastatin A4 analogs containing cyano and halogen, and relates to the field of medicinal compounds, wherein the structure of the combretastatin A4 analog is represented by the following formula defined in the specification. In the prior art, the selective anticancer activity compounds with characteristics of strong inhibition activity oncancer cells and no toxicity to normal cells are necessary to the generation of novel anticancer drugs while the compounds are absent. According to the present invention, based on the requirements inthe prior art, 11 series I combretastatin A4 analogs with fluorine, chlorine, bromine or trifluoromethyl at the ortho position, meta position or para position of the B ring, and 7 series II analogs are synthesized; in the series I compounds, when the para position of the B ring is substituted by fluorine, chlorine, bromine or trifluoromethyl, the good selective anticancer activity can be achieved,and the toxicity to L-02 normal cells is weak; when the para position is substituted by fluorine, chlorine or bromine, a ratio of the IC50 value in AGS cancer cells to the IC50 value in L-02 normal cells is greater than 100; when the para position is substituted by trifluoromethyl, a ratio of the IC50 value in MGC-803 cancer cells to the IC50 value in L-02 normal cells is greater than 100; and the selective anticancer activity of the four compounds is good.
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- Synthesis and characterisation of (Z)-styrylbenzene derivatives as potential selective anticancer agents
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To identify anticancer agents with high potency and low toxicity, a series of (Z)-styrylbenzene derivatives were synthesised and evaluated for anticancer activities using a panel of nine cancer cell lines and two noncancerous cell lines. Most derivatives exhibited significant anti-proliferative activities against five cancer cell lines, including MGC-803 and BEL-7402. (Z)-3-(p-Tolyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile (6h) showed a strong inhibitory effect on MGC-803 cells (IC50 50 50 value of 6h in L-02 cells was 10,000-fold higher than in MGC-803 cells. Compound 6h inhibited proliferation of BEL-7402 cells by arresting at the G2/M phase through up-regulation of cyclin B1 expression, down-regulation of cyclin A and D1 expression, and induction of apoptosis. In addition, 6h inhibited the migration of BEL-7402 cells and the formation of cell colonies.
- Xin, Ya-Bing,Li, Jia-Jun,Zhang, Hong-Jian,Ma, Jun,Liu, Xin,Gong, Guo-Hua,Tian, Yu-Shun
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p. 1554 - 1564
(2018/10/02)
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- TYD1608 with selective anti-cancer activity as well as preparation and application thereof
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The invention provides cyan-containing TYD1608, i.e., (Z)-3-(p-methyl phenyl)-2-(3,4,5-trimethoxyphenyl) acrylonitrile as well as preparation and application thereof, and relates to the field of medicinal compounds with the structure shown in the description. Various anti-cancer medicine in the prior art have the killing capability on cancer cells and also have great toxicity on normal cells; thetreatment of cancer patients is seriously influenced, so that the invention of the medicine with the selective anti-cancer activity on the normal cells is very important. The TYD1608 is synthesized; the compound shows strong proliferation inhibition capability on six kinds of human face cancer cells; in addition, the toxicity on the L-02 normal human liver cells is weak. The IC50 value on the MGC-803 gastric cancer cells is smaller than 0.01 mu M, is better than the clinic common use anti-cancer medicine of taxol; good selective anti-cancer activity is realized. Mechanism study shows that theproliferation inhibition activity of the TYD1608 on BEL-7402 cancer cells is the result of inhibiting the G2/M period in the cell period, inducting early stage and later stage apoptosis, blocking cellmigration, inhibiting cell period relevant protein cyclin A1 and cyclin D1.
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- Activity of resveratrol triesters against primary acute lymphoblastic leukemia cells
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Resveratrol is a common polyphenol of plant origin known for its cancer prevention and other properties. Its wider application is limited due to poor water solubility, low stability, and weak bioavailability. To overcome these limitations, a series of 13 novel resveratrol triesters were synthesized previously. In this paper, we describe the synthesis of 3 additional derivatives and the activity of all 16 against primary acute lymphoblastic leukemia cells. Of these, 3 compounds were more potent than resveratrol (IC50?=?10.5?μM) namely: resveratryl triacetate (IC50?=?3.4?μM), resveratryl triisobutyrate (IC50?=?5.1?μM), and resveratryl triisovalerate (IC50?=?4.9?μM); all other derivatives had IC50 values of >10?μM. Further studies indicated that the active compounds caused G1 phase arrest, increased expression of p53, and induced characteristics of apoptotic cell death. Moreover, the compounds were only effective in cycling cells, with cells arrested in G1 phase being refractory.
- Urbaniak, Alicja,Delgado, Magdalena,Kacprzak, Karol,Chambers, Timothy C.
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p. 2766 - 2770
(2017/05/29)
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- Agricultural bactericide derived from gallate, and application
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The invention provides an agricultural bactericide derived from gallate, and relates to the field of agricultural medicines. The main ingredient of the agricultural bactericide is gallate derivate, wherein the gallate derivate is prepared from a compound with a structure disclosed by a formula (I) and is provided with a hydrophilic functional group-phenolic hydroxyl group. According to the agricultural bactericide prepared from the gallate derivate, various crop harmful bacteria can be inhibited, and the agricultural bactericide especially has a good bacteriostatic effect on apple altermaria leaf spot, botryosphaeria dothidea, rhizoctonia solani, colletotrichum fragariae, potato blight and the like and has good water solubility, and the problem that the gallate derivate prepared in the prior art has poor water solubility is solved.
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- Transfer Hydrogenation of Carbonyl Derivatives Catalyzed by an Inexpensive Phosphine-Free Manganese Precatalyst
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A very simple and inexpensive catalytic system based on abundant manganese as transition metal and on an inexpensive phosphine-free bidendate ligand, 2-(aminomethyl)pyridine, has been developed for the reduction of a large variety of carbonyl derivatives with 2-propanol as hydrogen donor. Remarkably, the reaction proceeds at room temperature with low catalyst loading (down to 0.1 mol %) and exhibits a good tolerance toward functional groups. High TON (2000) and TOF (3600 h-1) were obtained.
- Bruneau-Voisine, Antoine,Wang, Ding,Dorcet, Vincent,Roisnel, Thierry,Darcel, Christophe,Sortais, Jean-Baptiste
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supporting information
p. 3656 - 3659
(2017/07/15)
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- 2-BENZYL-INDANONE COMPOUNDS AS ANTICANCER AGENT AND A PROCESS FOR PREPARATION THEREOF
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The anticancer activity of gallic acid compounds has been invented, in order to obtain new potent and cost effective molecule using in vitro cytotoxicity assay. The invention particularly relates to the gallic acid based new molecules i.e. 2-benzyl indanones represented by structure 1, possessing anticancer activity against human cancer cell lines. The compound also exhibited tubulin polymerisation inhibition. 2-(3',4'-methylenedioxybenzyl)-3-(3",4",5"-trimethoxyphenyl)-indanone- 1 (2), possessing molecular formulae as C29H30O9 was synthesized from gallic acid, exhibits potent in-vivo anticancer activity. Compound 2 was evaluated for acute oral activity in Swiss albino mice and it was found to be well tolerated by the experimental animals up to 300mg/kg body weight. (Formula 1, Formula 2).
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- Combretastatin A-4 Analogue: A Dual-Targeting and Tubulin Inhibitor Containing Antitumor Pt(IV) Moiety with a Unique Mode of Action
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Three new Pt(IV) complexes comprising a combretastatin A-4 analogue were designed and synthesized. The resulting antitumor Pt(IV) complexes could significantly improve the antiproliferative activity and overcome the drug resistance of cisplatin in vitro. Interestingly, these novel compounds not only can carry the DNA binding Pt(II) warhead into the cancer cells but also have a small molecule fragment that can inhibit tubulin polymerization. Among them, complex 13, which was attached to an inhibitor of tubulin at one axial position of Pt(IV) octahedral coordination sphere, could effectively enter cancer cells, arrest the cell cycle in HepG-2 cancer cells at G2/M phases, and induce activation of caspases triggering apoptotic signaling via the mitochondrial-dependent apoptosis pathways. Moreover, complex 13 has the ability to effectively inhibit the tumor growth in the HepG-2 xenograft model without causing significant loss of animal body weight in comparison with cisplatin.
- Huang, Xiaochao,Huang, Rizhen,Gou, Shaohua,Wang, Zhimei,Liao, Zhixin,Wang, Hengshan
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p. 2132 - 2148
(2016/09/28)
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- Asymmetric glycolate alkylation approach towards total synthesis of 8-O.6′ and 8-O.4′-neolignans
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The glycolate alkylation approach for the total synthesis of 8-O.6′ and 8-O.4′-neolignans has been optimized affording the natural products with high overall yields and excellent stereoselectivity. The developed approach can be further utilized towards the synthesis of many natural and unnatural neolignans. This is the first approach for the synthesis of neolignans using asymmetric glycolate alkylation approach.
- Gangar, Mukesh,Chouhan, Mangilal,Goyal, Sandeep,Harikrishnan,Chandran,Ittuveetil, Avinash,Nair, Vipin A.
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supporting information
p. 5931 - 5934
(2016/12/09)
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- Design, synthesis and antiproliferative activity of the new conjugates of E7010 and resveratrol as tubulin polymerization inhibitors
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A new class of (E)-N-phenyl-3-styrylpyridin-2-amine conjugates were designed and synthesized on the basis of E7010 and resveratrol scaffolds. These conjugates were evaluated for their antiproliferative activity in four human cancer cell lines with GI50 values ranging from 2.1 μM to 20 μM. Two of the conjugates RSV-1 and RSV-11 were found to possess 13-fold higher GI50 values than resveratrol and 1 to 2 fold higher GI50 values than E7010 against the human cervical HepG2 cancer line. They displayed high potency and selectivity in a panel of NCI 60 human cancer cell lines. Based on the GI50 values against the panel of 60 NCI cancer cell lines and dock scores from the molecular modelling studies, we selected RSV-1 and RSV-11 for tubulin polymerization and mechanistic studies. Furthermore, RSV-1 and RSV-11 compounds inhibited the assembly of tubulin by strongly binding to the colchicine-binding site. The G2/M-phase is arrested in HepG2 cells as assessed by flow cytometry. Structure based studies, western blotting and immunofluorescence experiments demonstrated that RSV-1 and RSV-11 depolymerize microtubules in the HepG2 cell line, resulting in an accumulation of G2/M cells.
- Kamal, Ahmed,Ashraf,Basha, Shaik Thokhir,Ali Hussaini,Singh, Shamshair,Vishnuvardhan,Kiran, Boppana,Sridhar, Balasubramanian
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p. 1382 - 1394
(2016/02/03)
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- CSJ acting as a versatile highly efficient greener resource for organic transformations
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Simple, new, greener and efficient alternatives to the existing protocols have been developed for the reduction of aromatic aldehydes to their corresponding alcohols, decarboxylation of substituted benzoic acids (C6-C1) and substituted cinnamic acids (C6-C3) with a hydroxyl group at the para position with respect to the acid group to corresponding phenolic compounds and vinyl phenols respectively by using a natural feedstock, cucumber juice (CSJ), which acts as a greener solvent system, performing a substrate-selective reaction. Additionally, the hydrolysis of the acetyl as well as the benzoyl group of aromatic compounds has been carried out to afford excellent yield by CSJ.
- Maity, Himadri Sekhar,Misra, Kaushik,Mahata, Tanushree,Nag, Ahindra
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p. 24446 - 24450
(2016/03/15)
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- Synthesis and Biological Evaluation of 1,2,3-triazole tethered Pyrazoline and Chalcone Derivatives
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A series of pyrazoline derivatives and corresponding chalcone intermediates with substituents same as combretastatin-A4(CA-4) conjugated with triazole nucleus has been synthesized and evaluated for their anticancer potential. Sulphorhodamine B(SRB) assay indicated compound 12c to be the most active compound from the series with GI50 value of 6.7 μm against the human liver carcinoma cell line HepG2. Interestingly, the intermediate 11c exhibited more promising cytotoxicity demonstrating GI50 value of 1.3 μm against the prostate cancer cell line DU145. Compounds 11c and 12c caused accumulation of cells in G2/M phase and inhibited tubulin polymerization. Furthermore, these compounds reduce the mitochondrial membrane potential and activate caspases 3 and 9, thereby indicating their ability to trigger apoptosis.
- Hussaini, Syed Mohammed Ali,Yedla, Poornachandra,Babu, Korrapati Suresh,Shaik, Thokhir B.,Chityal, Ganesh Kumar,Kamal, Ahmed
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- New inhibitors of tyrosyl-DNA phosphodiesterase I (Tdp 1) combining 7-hydroxycoumarin and monoterpenoid moieties
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A number of derivatives of 7-hydroxycoumarins containing aromatic or monoterpene substituents at hydroxy-group were synthesized based on a hit compound from a virtual screen. The ability of these compounds to inhibit tyrosyl-DNA phosphodiesterase I (Tdp 1), important target for anti-cancer therapy, was studied for the first time. It was found that the 7-hydroxycoumarin derivatives with monoterpene pinene moiety are effective inhibitors of Tdp 1 with the most active derivative (+)-25c with IC50value of 0.675?μM. This compound has low cytotoxicity (CC50?>100?μM) when tested against human cancer cells which is crucial for presupposed application in combination with clinically established anticancer drugs. The ability of the new compounds to enhance the cytotoxicity of camptothecin, an established topoisomerase 1 poison, was demonstrated.
- Khomenko, Tatyana,Zakharenko, Alexandra,Odarchenko, Tatyana,Arabshahi, Homayon John,Sannikova, Victoriya,Zakharova, Olga,Korchagina, Dina,Reynisson, Jóhannes,Volcho, Konstantin,Salakhutdinov, Nariman,Lavrik, Olga
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p. 5573 - 5581
(2016/10/24)
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- Selective acetylation of primary alcohols by ethyl acetate
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A KOtBu and ethyl acetate mediated efficient methodology has been developed for the acetylation of primary and secondary alcohols where ethyl acetate is the source of acetyl group. The reaction is fast, mild, efficient, and highly selective towards the primary alcohols.
- Singha, Raju,Ray, Jayanta K.
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supporting information
p. 5395 - 5398
(2016/11/11)
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- Anticancer activity of gallic acid template-based benzylidene indanone derivative as microtubule destabilizer
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Benzylidene indanones have been designed and synthesized from gallic acid, a plant phenolic acid as possible anticancer agent. The best analogue of the series, that is, 3-(3′,4′,5′-trimethoxyphenyl)-4,5,6-trimethoxy-2-(4?-nitrobenzylidene)-indan-1-one (8) exhibited potent cytotoxicity (IC50=3–10?μm) against several human cancer cell lines through microtubule destabilization (IC50=1.54?μm) after occupying colchicine-binding site of β-tubulin. In cell cycle analysis, compound 8 exerted G2/M phase arrest in both MCF-7 and MDA-MB-231 cells and induced apoptosis. It reduced 34.8% solid tumor in in vivo Ehrlich ascite carcinoma in Swiss albino mice at 30?mg/kg dose. In acute oral toxicity experiment, it was tolerable up to 300?mg/kg doses in Swiss albino mice. The lead compound 8 needs to be optimized for better activity.
- Singh, Aastha,Fatima, Kaneez,Srivastava, Ankita,Khwaja, Sadiya,Priya, Dev,Singh, Arjun,Mahajan, Girish,Alam, Sarfaraz,Saxena, Ajit K.,Mondhe,Luqman, Suaib,Chanda, Debabrata,Khan, Feroz,Negi, Arvind S.
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p. 625 - 634
(2016/10/25)
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- Hydrogenation of Esters to Alcohols Catalyzed by Defined Manganese Pincer Complexes
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The first manganese-catalyzed hydrogenation of esters to alcohols has been developed. The combination of Mn(CO)5Br with [HN(CH2CH2P(Et)2)2] leads to a mixture of cationic and neutral Mn PNP pincer complexes, which enable the reduction of various ester substrates, including aromatic and aliphatic esters as well as diesters and lactones. Notably, related pincer complexes with isopropyl or cyclohexyl substituents showed very low activity.
- Elangovan, Saravanakumar,Garbe, Marcel,Jiao, Haijun,Spannenberg, Anke,Junge, Kathrin,Beller, Matthias
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supporting information
p. 15364 - 15368
(2016/12/03)
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- Design and synthesis of a series of serine derivatives as small molecule inhibitors of the SARS coronavirus 3CL protease
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Synthesis of serine derivatives having the essential functional groups for the inhibitor of SARS 3CL protease and evaluation of their inhibitory activities using SARS 3CL R188I mutant protease are described. The lead compounds, functionalized serine derivatives, were designed based on the tetrapeptide aldehyde and Bai's cinnamoly inhibitor, and additionally performed with simulation on GOLD softwear. Structure activity relationship studies of the candidate compounds were given reasonable inhibitors ent-3 and ent-7k against SARS 3CL R188I mutant protease. These inhibitors showed protease selectivity and no cytotoxicity.
- Konno, Hiroyuki,Wakabayashi, Masaki,Takanuma, Daiki,Saito, Yota,Akaji, Kenichi
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supporting information
p. 1241 - 1254
(2016/03/01)
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- Synthesis and anti-inflammatory activity of phenylbutenoid dimer analogs
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Several phenylbutenoid dimer (PBD) analogs were synthesized and evaluated for their inhibitory activities against nitric oxide (NO) production and TNF-α release. The PBD analogs were synthesized via Diels - Alder and subsequent Schlosser reactions as key steps. Among the tested compounds, two analogs (8c, 8f) exhibited much stronger inhibitory activity against LPS-stimulated NO production and TNF-α release in RAW 264.7 cells than that of wogonin.
- Kim, Sung-Soo,Fang, Yuanying,Park, Haeil
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supporting information
p. 1676 - 1680
(2015/07/15)
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- Cytotoxic activities and metabolic studies of new combretastatin analogues
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A new series of combretastatin analogues with B-ring modifications were synthesized and evaluated for their cytotoxicity against one endothelial (HUVEC) and three tumor cell lines, e.g., the LoVo colon, the PC-3 prostate, and the U373 glioma cancer models. These new combretastatin analogues showed differential cytotoxic activities, cis derivatives 13 5-(2-Z-trimethoxyphenylethenyl)benzo[1,2-c]1,2,5-oxadiazole N 1-oxide and 14 5-(2-Z-trimethoxyphenylethenyl)benzo[1,2,5]thiadiazole exhibiting interesting cytotoxicity both on endothelial and on tumor cells. Unlike the cis benzofurazan 12 5-(2-Z-trimethoxyphenylethenyl)benzo[1,2-c]1,2,5-oxadiazole, induction of apoptosis by 13 appeared to be through caspase-3 activation. Metabolic investigations showed a positive correlation between highly metabolized compounds and cytotoxic activity, suggesting that highly cytotoxic derivatives may act as pro-drug via a reductive metabolization to more active metabolites.
- Macé, Yohan,Bony, Emilie,Delvaux, David,Pinto, Adan,Mathieu, Véronique,Kiss, Robert,Feron, Olivier,Quetin-Leclercq, Jo?lle,Riant, Olivier
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p. 3143 - 3156
(2015/08/03)
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- Highly chemoselective hydrogenation of active benzaldehydes to benzyl alcohols catalyzed by bimetallic nanoparticles
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By using novel Pd/Ni bimetallic nanoparticles as a catalyst, the active benzaldehydes were hydrogenated to the corresponding benzyl alcohols as unique products in practical quantitative yields. The undesired catalytic hydrogenolysis of the benzyl alcohol was inhibited completely. By using this hydrogenation as a key step, the total synthesis of the natural product gastrodin was achieved with less total steps and a higher total yield.
- Liu, Chulong,Bao, Hailin,Wang, Dingsheng,Wang, Xinyan,Li, Yadong,Hu, Yuefei
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p. 6460 - 6462
(2015/11/16)
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