- Design, synthesis and biological evaluation of novel 4-substituted coumarin derivatives as antitumor agents
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Herein, fifteen new compounds containing coumarin, 1,2,3-triazole and benzoyl-substituted arylamine moieties were designed, synthesized and tested in vitro for their anticancer activity. The results showed that all tested compounds had moderate antiproliferative activity against MDA-MB-231, a human breast cancer cell line, under both normoxic and hypoxic conditions. Furthermore, the 4-substituted coumarin linked with benzoyl 3,4-dimethoxyaniline through 1,2,3-triazole (compound 5e) displayed the most prominent antiproliferative activities with an IC50 value of 0.03 μM, about 5000 times stronger than 4-hydroxycoumarin (IC50 > 100 μM) and 20 times stronger than doxorubicin (IC50 = 0.60 μM). Meanwhile, almost all compounds revealed general enhancement of proliferation-inhibiting activity under hypoxia, contrasted with normoxia. A docking analysis showed that compound 5e had potential to inhibit carbonic anhydrase IX (CA IX).
- An, Ran,Hou, Zhuang,Li, Jian-Teng,Yu, Hao-Nan,Mou, Yan-Hua,Guo, Chun
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Read Online
- Isolation of molybdenum(vi) from simulated leachates of irradiated uranium-aluminum targets using diluted and undiluted sulfate ionic liquids
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A method is presented to separate molybdenum from other elements commonly present in oxidative alkaline leachates of irradiated uranium-aluminum targets for the production of molybdenum-99. The separation was accomplished by selective extraction of molybdate anions using triazolium and phosphonium sulfate ionic liquid extractants, either diluted in 1-octanol or undiluted. Molybdenum was then stripped from the organic phase using a sodium hydrogen carbonate solution. The extractant was regenerated by contacting the organic phase with an alkaline sulfate solution. The extraction mechanism and the influence of the diluent on the extractant performance were investigated. The reported method provides a promising alternative to state-of-the-art chromatographic processes, showing potential for limiting the production of radioactive waste.
- Raiguel, Stijn,Dehaen, Wim,Binnemans, Koen
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Read Online
- Combinatorial synthesis of new fluorescent scaffolds using click chemistry
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Azides and acetylenes are bio-orthogonal functional groups that can be readily coupled using copper(I)- or ruthenium(II)- catalyzed 1,3-dipolar cycloaddition reactions. Using non-fluorescent aromatic azides and aromatic acetylenes, covering a range of electron rich and poor building blocks, the Huisgen cycloaddition afford 1,4-disubstituted or 1,5-disubstituted 1,2,3-triazoles. Using a combinatorial approach by running reaction in parallel in polypropylene 96-well plates we discovered several new fluorescent 1,2,3-triazoles scaffolds. These compounds show diverse interactions with biomolecules that could find applications in biology in, for example, fluorescence microscopy or biomolecule quantification.
- Cleemann, Felix,Karuso, Peter,Kum-Cheung, Wendy Loa
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supporting information
(2021/12/08)
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- Nickel Boride Catalyzed Reductions of Nitro Compounds and Azides: Nanocellulose-Supported Catalysts in Tandem Reactions
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Nickel boride catalyst prepared in situ from NiCl2 and sodium borohydride allowed, in the presence of an aqueous solution of TEMPO-oxidized nanocellulose (0.01 wt%), the reduction of a wide range of nitroarenes and aliphatic nitro compounds. Here we describe how the modified nanocellulose has a stabilizing effect on the catalyst that enables low loading of the nickel salt pre-catalyst. Ni-B prepared in situ from a methanolic solution was also used to develop a greener and facile reduction of organic azides, offering a substantially lowered catalyst loading with respect to reported methods in the literature. Both aromatic and aliphatic azides were reduced, and the protocol is compatible with a one-pot Boc-protection of the obtained amine yielding the corresponding carbamates. Finally, bacterial crystalline nanocellulose was chosen as a support for the Ni-B catalyst to allow an easy recovery step of the catalyst and its recyclability for new reduction cycles.
- Proietti, Giampiero,Prathap, Kaniraj Jeya,Ye, Xinchen,Olsson, Richard T.,Dinér, Peter
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supporting information
p. 133 - 146
(2021/11/04)
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- Direct 3-Acylation of Indolizines by Carboxylic Acids for the Practical Synthesis of Red Light-Releasable Caged Carboxylic Acids
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To enhance the practicality of photouncaging system using 3-acyl-2-methoxyindolizines, direct acylation of indolizines with carboxylic acids was developed using condensation reagents, generally used for peptide coupling. This method allowed for caging a broad range of carboxylic acids with indolizines. The method enabled a facile synthesis of water-soluble caged bioactive carboxylic acids having an intramolecular photosensitizer. The efficient release of carboxylic acids from the synthesized caged compounds upon red light irradiation was confirmed in neutral buffered solutions.
- Watanabe, Kenji,Terao, Nodoka,Niwa, Takashi,Hosoya, Takamitsu
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p. 11822 - 11834
(2021/07/31)
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- Synthesis of Azaylide-Based Amphiphiles by the Staudinger Reaction
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Catalyst- and reagent-free reactions are powerful tools creating various functional molecules and materials. However, such chemical bonds are usually hydrolysable or require specific functional groups, which limits their use in aqueous media. Herein, we report the development of new amphiphiles through the Staudinger reaction. Simple mixing of chlorinated aryl azide with a hydrophilic moiety and various triarylphosphines (PAr3) gave rise to azaylide-based amphiphiles NPAr3, rapidly and quantitatively. The obtained NPAr3 formed ca. 2 nm-sized spherical aggregates (NPAr3)n in water. The hydrolysis of NPAr3 was significantly suppressed as compared with those of non-chlorinated amphiphiles nNPAr3. Computational studies revealed that the stability is mainly governed by the decrease in LUMO around the phosphorus atom owing to the o-substituted halogen groups. Furthermore, hydrophobic dyes such as Nile red and BODIPY were encapsulated by the spherical aggregates (NPAr3)n in water.
- Kishida, Natsuki,Suzuki, Hayate,Toyota, Shinji,Yamashina, Masahiro,Yoshizawa, Michito
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supporting information
p. 17915 - 17919
(2021/07/09)
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- Antiviral activity of 1,4-disubstituted-1,2,3-triazoles against HSV-1 in vitro
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Background: Herpes simplex virus 1 (HSV-1) affects a large part of the adult population. Anti-HSV-1 drugs, such as acyclovir, target thymidine kinase and viral DNA polymerase. However, the emerging of resistance of HSV-1 alerts for the urgency in developing new antivirals with other therapeutic targets. Thus, this study evaluated a series of 1,4-disubstituted-1,2,3-triazole derivatives against HSV-1 acute infection and provided deeper insights into the possible mechanisms of action. Methods: Human fibroblast cells (HFL-1) were infected with HSV-1 17syn+ and treated with the triazole compounds at 50 mM for 24 h. The 50% effective drug concentration (EC50) was determined for the active compounds. Their cytotoxicity was also evaluated in HFL-1 with the 50% cytotoxic concentration (CC50) determined using CellTiter-Glo solution. The most promising compounds were evaluated by virucidal activity and influence on virus egress, DNA replication and transcription, and effect on an acyclovir-resistant HSV-1 strain. Results: Compounds 3 ((E)-4-methyl-N'-(2-(4(phenoxymethyl)-1H-1,2,3-triazol1yl)benzylidene)benzenesulfonohydrazide) and 4 (2,2'-(4,4'-((1,3-phenylen ebis(oxy))bis(methylene))bis(1H-1,2,3-triazole-4,1 diyl)) dibenzaldehyde) were the most promising, with an EC50 of 16 and 21 mM and CC50 of 285 and 2,593 mM, respectively. Compound 3 was able to inhibit acyclovir-resistant strain replication and to interfere with virus egress. Both compounds did not affect viral DNA replication, but inhibited significantly the expression of ICP0, ICP4 and gC. Compound 4 also affected the transcription of UL30 and ICP34.5. Conclusions: Our findings demonstrated that these compounds are promising antiviral candidates with different mechanisms of action from acyclovir and further studies are merited.
- Viegas, Daiane J.,da Silva, Ver?nica D.,Buarque, Camilla D.,Bloom, David C.,Abreu, Paula A.
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p. 399 - 410
(2021/05/31)
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- Benzimidazole–galactosides bind selectively to the Galectin-8 N-Terminal domain: Structure-based design and optimisation
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We have obtained the X-ray crystal structure of the galectin-8 N-terminal domain (galectin-8N) with a previously reported quinoline–galactoside ligand at a resolution of 1.6 ?. Based on this X-ray structure, a collection of galactosides derivatised at O3 with triazole, benzimidazole, benzothiazole, and benzoxazole moieties were designed and synthesised. This led to the discovery of a 3-O-(N-methylbenzimidazolylmethyl)–galactoside with a Kd of 1.8 μM for galectin-8N, the most potent selective synthetic galectin-8N ligand to date. Molecular dynamics simulations showed that benzimidazole–galactoside derivatives bind the non-conserved amino acid Gln47, accounting for the higher selectivity for galectin-8N. Galectin-8 is a carbohydrate-binding protein that plays a key role in pathological lymphangiogenesis, modulation of the immune system, and autophagy. Thus, the benzimidazole-derivatised galactosides represent promising compounds for studies of the pathological implications of galectin-8, as well as a starting point for the development of anti-tumour and anti-inflammatory therapeutics targeting galectin-8.
- Hassan, Mujtaba,van Klaveren, Sjors,H?kansson, Maria,Diehl, Carl,Kova?i?, Rebeka,Baussière, Floriane,Sundin, Anders P.,Dernov?ek, Jaka,Walse, Bj?rn,Zetterberg, Fredrik,Leffler, Hakon,Anderluh, Marko,Toma?i?, Tihomir,Jakopin, ?iga,Nilsson, Ulf J.
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- Discovery of triazolyl thalidomide derivatives as anti-fibrosis agents
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Fibrosis with excessive accumulation of extracellular matrix (ECM) often causes progressive organ dysfunction and results in many inflammatory and metabolic diseases, including systemic sclerosis, pulmonary fibrosis, advanced liver disease and advanced kidney disease. The store-operated calcium entry (SOCE) pathway and the related signaling pathway were both found to be the important routes for fibrogenesis. Our aim in this study was to discover novel compounds to inhibit fibrogenesis. A number of triazolyl thalidomide derivatives were synthesized and evaluated for their anti-fibrosis activities. Compounds 7b-e, 8c-d, 10a-b and 10e inhibited intracellular Ca2+ activation and showed no cytotoxicity. Among them, 6-{4-[(3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl)methyl]-1H-1,2,3-triazol-1-yl}hexanoic acid (10e) with the most potent inhibitory effect was chosen for further examination. The results revealed that compound 10e, a SOCE inhibitor, reversed the migratory ability of TGF-β1-induced myofibroblasts, dedifferentiated myofibroblasts to fibroblasts due to cytoskeleton remodeling, and restrained myofibroblast activation by targeting Orai1 and TGF-β1/SMAD2/3 signaling pathways. The in silico study indicated that compound 10e, with the appropriate lipophilic carbon chain and carboxylic acid, showed a good drug-likeness model score. Conclusively, the SOCE inhibitor, compound 10e, is used as a promising lead compound for the development of a new treatment for fibrosis. This journal is
- Tang, Kai-Wei,Hsu, Wen-Li,Chen, Cheng-Ru,Tsai, Ming-Hsien,Yen, Chia-Jung,Tseng, Chih-Hua
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p. 3589 - 3599
(2021/03/03)
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- Design, click conventional and microwave syntheses, DNA binding, docking and anticancer studies of benzotriazole-1,2,3-triazole molecular hybrids with different pharmacophores
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Despite the availability of some drugs, there is an urgent need for effective anti-cancer medication. It is due to various side effects and non-functionality of the present drugs; especially at the late stage of cancer. Therefore, three series (4a-e, 6a-e and 8a-j; 21 compounds) of benzotriazole-1,2,3-triazole hybrids (carrying different pharmacophores) have been designed and synthesized (by both conventional and microwave syntheses) through the Cu(I)-catalyzed click 1,3-dipolar cycloaddition reaction of the propargylated benzotriazole with the appropriate aliphatic, aromatic and phenyl/benzyl acetamide azides. The syntheses times were from 6 to 12 h and 4 to 8 min in conventional and microwave syntheses. The yields were 80 to 86percent and 89 to 95percent in conventional and microwave syntheses; confirming microwave synthesis as an economic and eco-friendly method. These compounds were characterized by proper spectroscopic methods. The anticancer activities with A549 and H1299 lung cancer cell lines were in the range of 70.0 to 90.0percent for 4a-e series, 78.0 to 90.0percent for 6a-e series and 81.0 to 90.0percent for 8a-j series. The reported compounds showed good DNA binding constants in the range of 1.3 × 103 to 11.90 × 105 M?1. The docking results suggested strong DNA bindings of the reported compounds in the minor grooves of DNA; through hydrogen bonding and hydrophobic interactions. The quite good anticancer activities and high DNA binding constants have indicated that the reported molecules may be future anticancer agents.
- Alharbi, Khalid,Ali, Imran,Aljuhani, Ateyatallah,Alraqa, Shaya Yahya,Aouad, Mohamed Reda,Rezki, Nadjet
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- CHEMOSELECTIVE SENSITIVITY BOOSTER FOR TAGGING A PEPTIDE, PEPTIDE CONJUGATE, OR SIMILAR REACTIVE MOLECULE
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The invention pertains to chemoselective sensitivity booster for tagging a peptide, peptide conjugate, or similar reactive molecule for analysis of a peptide, protein, antibody, protein bioconjugate, antibody bioconjugate, and similar analytes. The sensitivity booster comprises of sp2 or sp3 nitrogen centers in combination with hydrophobic carbon chains linked with an electrophile or nucleophile for attachment with a peptide, peptide conjugate, or molecules with similar reactivity.
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Page/Page column 24
(2020/12/29)
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- Structural modification of the aryl sulfonate ester of cjoc42 for enhanced gankyrin binding and anti-cancer activity
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Gankyrin is an oncogenic protein involved in various biological processes, such as cellular growth and proliferation. Its overexpression in certain cancers results in an increase of gankyrin-mediated protein-protein interactions (PPIs), leading to cancer proliferation. To date, only one small molecule (cjoc42) has been identified to bind gankyrin, which simultaneously inhibits its interaction with the 26S proteasome. Despite this advance, 2nd generation inhibitors are needed to improve gankyrin binding and cellular efficacy. To this end, an extensive SAR for the aryl sulfonate ester moiety of the cjoc42 scaffold was explored, and showed that substitutions at the 2-, 3-, and 4-positions manifested significant increases in gankyrin binding, resulting in the most potent binders of gankyrin to date. Subsequent cell-based assay evaluation of our derivatives demonstrated antiproliferative activity against pediatric liver cancer cell lines Hep3B and HepG2, which was not previously observed for cjoc42.
- Kanabar, Dipti,Farrales, Pamela,Gnanamony, Manu,Almasri, Joseph,Abo-Ali, Ehab M.,Otmankel, Younos,Shah, Henna,Nguyen, Dawn,El Menyewi, Mark,Dukhande, Vikas V.,D'Souza, Amber,Muth, Aaron
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supporting information
(2020/01/06)
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- New α-Hydroxy-1,2,3-triazoles and 9H-Fluorenes-1,2,3-triazoles: H Synthesis and Evaluation as Glycine Transporter 1 Inhibitors
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Two series of new compounds containing 1,2,3-triazole moiety were designed as putative GlyT1 inhibitors aiming the discovery of new hits with activity in cognitive disorders. 1,4-Disubstituted α-hydroxy-1,2,3-triazoles were obtained as racemates in moderate to good yields by the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction (click chemistry) as the key step between propargyl alcohols and aryl azides, previously prepared from anilines or boronic acids. Benzo[c]chromene-triazoles were planned to be obtained by palladium-catalyzed C?H activation using [bis(trifluoroacetoxy)iodobenzene] (PhI(TFA)2) of some α-hydroxy-1,2,3-triazoles, since benzo[c]chromenes are also privileged groups with several biological activities, including to the central nervous system. Unexpectedly, 9H-fluorenes-1,2,3-triazoles, instead of benzo[c]chromenetriazoles, were obtained by Friedel-Crafts alkylation reaction. The two series of compounds were tested for inhibition of the glycine transporter (rat GlyT1 isoform) but only the α-hydroxy-1,2,3-triazole 9b was active (half maximal inhibitory concentration (IC50) = 8.0 μM).
- Buarque, Camilla D.,Guimar?es, Marilia Z.,López?Corcuera, Beatriz,Neto, Jo?o Gon?alves,No?l, Fran?ois,Silva, Rafaela R.,da Silva, Veronica D.
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p. 1258 - 1269
(2020/10/14)
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- Biofilm inhibition and DNA binding studies of isoxazole-triazole conjugates in the development of effective anti-bacterial agents
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Isoxazole-triazole conjugates (8a-q) were synthesized using click chemistry approach and their biological activities were explored to develop novel antibacterial agents. In vitro antibacterial screening against Gram-positive as well as Gram-negative bacterial strains identified compounds 8b and 8m with potent inhibitory potential against selective bacterial cells. 8b showed IC50 value of 67.6 μg/mL against P. aeruginosa while 8m exhibited better activity against Gram-positive bacteria S. pneumoniae and E. faecalis having IC50 values 74.13 and 44.7 μg/mL, respectively. Effect on growth kinetics of the bacterial cells as well as cytotoxicity studies on human embryonic kidney cells (HEK293) further supports their biological potential. Compound 8m significantly inhibited biofilm formation of E. coli cells visualized by scanning electron microscopy (SEM) analysis. The interaction of these compounds with ctDNA, as their possible mode of action, was studied using multi-spectroscopic techniques and molecular docking. The data suggested that compound 8m intercalate in the minor groove of DNA.
- Habib, Farhat,Alam, Shadab,Hussain, Afzal,Aneja, Babita,Irfan, Mohammad,Alajmi, Mohamed F.,Hasan, Phool,Khan, Parvez,Rehman, Md Tabish,Noman, Omar Mohammed,Azam, Amir,Abid, Mohammad
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- Design, synthesis & biological evaluation of ferulic acid-based small molecule inhibitors against tumor-associated carbonic anhydrase IX
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Carbonic anhydrase IX (CAIX) is an emerging drug target for hypoxia associated cancers. To identify potent and selective inhibitors of CAIX, a small library of ferulic acid (FA) derivatives bearing triazole moiety has been designed, synthesized and evaluated against different human CA isoforms (CAII, CAVA & CAIX). Though most of the compounds showed CAIX inhibition in the micromolar range, compound 7i selectively inhibits CAIX in the nanomolar range (IC50 = 24 nM). In silico analysis revealed binding of 7i with the catalytically important amino acid residues of CAIX. Further, cell-based studies indicate that 7i inhibits the activity of CAIX, decreases the epithelial to mesenchymal transitions, induces apoptosis, inhibits cell migration and colonization potential of cancer cells. Taken together, these results emphasized the use of 7i as a prospective pharmacological lead molecule in CAIX targeted anticancer therapeutics.
- Abid, Mohammad,Alajmi, Mohamed F.,Aneja, Babita,Daniliuc, Constantin G.,Hasan, Phool,Hassan, Md. Imtaiyaz,Hussain, Afzal,Khan, Parvez,Mohsin, Mohd.,Queen, Aarfa,Rizvi, M. Moshahid A.,Shamsi, Farheen
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- Heterogeneous photocatalysis of azides: Extending nitrene photochemistry to longer wavelengths
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The photodecomposition of azides to generate nitrenes usually requires wavelengths in the 300 nm region. In this study, we show that this reaction can be readily performed in the UVA region (368 nm) when catalyzed by Pd-decorated TiO2. In aqueous medium the reaction leads to amines, with water acting as the H source; however, in non-protic and non-nucleophilic media, such as acetonitrile, nitrenes recombine to yield azo compounds, while azirine-mediated trapping occurs in the presence of nucleophiles. The heterogeneous process facilitates catalyst separation while showing great chemoselectivity and high yields.
- Argüello, Juan E.,Lanterna, Anabel E.,Lemir, Ignacio D.,Scaiano, Juan C.
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supporting information
p. 10239 - 10242
(2020/10/02)
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- Synthesis and Antitrypanosomal Activity of 1,4-Disubstituted Triazole Compounds Based on a 2-Nitroimidazole Scaffold: a Structure-Activity Relationship Study
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Chagas disease affects 6–8 million people worldwide, remaining a public health concern. Toxicity, several adverse effects and inefficiency in the chronic stage of the disease are the major challenges regarding the available treatment protocols. This work involved the synthesis of twenty-two 1,4-disubstituted-1,2,3-triazole analogues of benznidazole (BZN), by using a click chemistry strategy. Analogues were obtained in moderate to good yields (40-97 %). Antitrypanosomal activity was evaluated against the amastigote forms of Trypanosoma cruzi. Compound 8 a (4-(2-nitro-1H-imidazol-1-yl)methyl)-1-phenyl-1H-1,2,3-triazole) without substituents on phenyl ring showed similar biological activity to BZN (IC50=3.0 μM, SI>65.3), with an IC50=3.1 μM and SI>64.5. Compound 8 o (3,4-di-OCH3?Ph) with IC50 = 0.65 μM was five-fold more active than BZN, and showed an excellent selectivity index (SI>307.7). Compound 8 v (3-NO2, 4-CH3?Ph) with IC50=1.2 μM and relevant SI>166.7, also exhibited higher activity than BZN. SAR analysis exhibited a pattern regarding antitrypanosomal activity relative to BZN, in compounds with electron-withdrawing groups (Hammett σ+) at position 3, and electron-donating groups (Hammett σ-) at position 4, as observed in 8 o and 8 v. Further research might explore in vivo antitrypanosomal activity of promising analogues 8 a, 8 o, and 8 v. Overall, this study indicates that approaches such as the bioisosteric replacement of amide group by 1,2,3-triazole ring, the use of click chemistry as a synthesis strategy, and design tools like Craig-plot and Topliss tree are promising alternatives to drug discovery.
- Assun??o, Elvis L. F.,Carvalho, Diego B.,das Neves, Amarith R.,Kawasoko Shiguemotto, Cristiane Y.,Portapilla, Gisele B.,de Albuquerque, Sergio,Baroni, Adriano C. M.
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p. 2019 - 2028
(2020/09/21)
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- Sensitivity booster for mass detection enables unambiguous analysis of peptides, proteins, antibodies, and protein bioconjugates
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A chemical tag enhances peptide detection by multiple orders in mass spectrometry. The substantial improvement in the peptide mapping along with simplified and enhanced fragmentation pattern enables the unambiguous sequencing of a protein and antibody. The chemoselective sensitivity booster provides a tool for remarkably improved analysis of protein bioconjugates.
- Singudas, Rohith,Reddy, Neelesh C.,Rai, Vishal
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supporting information
p. 9979 - 9982
(2019/08/22)
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- Design, synthesis and anti-platelet aggregation activity study of ginkgolide-1,2,3-triazole derivatives
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Ginkgolides are the major active component of Ginkgo biloba for inhibition of platelet activating factor receptor. An azide-alkyne Huisgen cycloaddition reaction was used to introduce a triazole nucleus into the target ginkgolide molecules. A series of ginkgolide-1,2,3-triazole conjugates with varied functional groups including benzyl, phenyl and heterocycle moieties was thus synthesized. Many of the designed derivatives showed potent antiplatelet aggregation activities with IC50 values of 5~21 nM.
- Cui, Jian,Hu, Lean,Shi, Wei,Cui, Guozhen,Zhang, Xumu,Zhang, Qing-Wen
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- Synthesis, structure, and synthetic potential of arenediazonium trifluoromethanesulfonates as stable and safe diazonium salts
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Aromatic diazonium salts are valuable building blocks for organic synthesis; however, in most cases, they are unstable, unsafe, poorly soluble, and/or expensive. In this paper, we have shown that a variety of stable and safe arenediazonium triflates ArN2+ TfO– can be obtained easily and in high yields by diazotization of anilines with tert-butyl nitrite in the presence of trifluoromethanesulfonic acid. Arenediazonium triflates are relatively shelf-stable in the dry state. They dissolve well in water, as well as polar and even nonpolar organic solvents. Less than 800 J/g of energy is released during the thermal decomposition of these salts, which indicates their explosion safety. Arenediazonium triflates have a high reactivity in the known reactions of diazonium chemistry, and undergo an unusual metal-free chlorodediazonization reaction with chloroform and CCl4.
- Filimonov, Victor D.,Krasnokutskaya, Elena A.,Kassanova, Assia Zh.,Fedorova, Valentina A.,Stankevich, Ksenia S.,Naumov, Nikolay G.,Bondarev, Alexander A.,Kataeva, Veronika A.
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p. 665 - 674
(2018/09/14)
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- Design, synthesis, and anti-bacterial evaluation of triazolyl-pterostilbene derivatives
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Staphylococcus aureus resistance to current antibiotics has become the greatest global challenge facing public health. The development of new antimicrobial agents is urgent and important and is needed to provide additional therapeutic options. In our previous study, we found out that pterostilbene exhibited potent antibacterial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA). According to previous studies, 1,2,3-triazole, with the characteristic of increasing the interaction with the target readily and enhancing water solubility, were widely used in the approved anti-bacterial drugs. Therefore, these results attract our interest to use the structure of pterostilbene as a scaffold for the hybrid 1,2,3-triazole moiety to develop a novel anti-MRSA infection agent. In this study, we demonstrated the design and synthesis of a series of triazolylpterostilbene derivatives. Among these compounds, compound 4d exhibited the most potent anti-MRSA activity with a minimum inhibitory concentration (MIC) value of 1.2-2.4 μg/mL and a minimum bactericidal concentration (MBC) value of 19.5-39 μg/mL. The structure-activity relationship and antibacterial mechanism were investigated in this study. Molecular docking studies were carried out to verify and rationalize the biological results. In this study, the results confirmed that our design could successfully increase the inhibitory activity and specificity against MRSA. Compound 4d could be used as a candidate for anti-bacterial agents and in depth vivo studies should be further investigated.
- Tang, Kai-Wei,Yang, Shih-Chun,Tseng, Chih-Hua
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- Identification of highly potent and selective Cdc25 protein phosphatases inhibitors from miniaturization click-chemistry-based combinatorial libraries
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Cell division cycle 25 (Cdc25) protein phosphatases play key roles in the transition between the cell cycle phases and their association with various cancers has been widely proven, which makes them ideal targets for anti-cancer treatment. Though several Cdc25 inhibitors have been developed, most of them displayed low activity and poor subtype selectivity. Therefore, it is extremely important to discover novel small molecule inhibitors with potent activities and significant selectivity for Cdc25 subtypes, not only served as drugs to treat cancer but also to probe its mechanism in transitions. In this study, miniaturized parallel click chemistry synthesis via CuAAC reaction followed by in situ biological screening were used to discover selective Cdc25 inhibitors. The bioassay results showed that compound M2N12 proved to be the most potent Cdc25 inhibitor, which also act as a highly selective Cdc25C inhibitor and was about 9-fold potent than that of NSC 663284. Moreover, M2N12 showed remarkable anti-growth activity against the KB-VIN cell line, equivalent to that of PXL and NSC 663284. An all-atom molecular dynamics (MD) simulation approach was further employed to probe the significant selectivity of M2N12 for Cdc25C relative to its structural homologs Cdc25A and Cdc25B. Overall, above results make M2N12 a promising lead compound for further investigation and structural modification.
- Jing, Lanlan,Wu, Gaochan,Hao, Xia,Olotu, Fisayo A.,Kang, Dongwei,Chen, Chin Ho,Lee, Kuo-Hsiung,Soliman, Mahmoud E.S.,Liu, Xinyong,Song, Yuning,Zhan, Peng
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- Synthesis and structures of zwitterionic polymers to induce electrostatic interaction with PDMS surface treated by air-plasma
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Various zwitterionic polymers, sulfobetaine and phosphoryl choline derivatives were synthesized in order to investigate zwitterionic polymer structures toward surface modification of PDMS, where the adsorption of zwitterionic polymers on polydimethylsiloxane surface treated with air-plasma was induced by the electrostatic interaction,. The electrostatic interaction was evaluated with hydrophilicity. The results suggested that a sulfobetaine polymer with higher molecular weight, lower molecular weight distribution, and shorter alkyl chain afforded high electrostatic interaction. A sulfobetaine polymer bearing phenylazide group showed similar electrostatic interaction with the PDMS surface, and it is a promising material for surface modification ofpolydimethylsiloxane.
- Tanaka, Mutsuo,Hirata, Yoshiki,Sawaguchi, Takahiro,Kurosawa, Shigeru
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p. 330 - 343
(2018/06/29)
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- Multi-Gram Scale Synthesis of 1,2,3-Triazolium Ionic Liquids and Assay of Their Resistance towards Bases
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An easily upscalable synthesis method for 1,2,3-triazolium ionic liquids is presented. Several ionic liquids were synthesized and characterized. The influence of the side chain structure on the base-stability was investigated. One example, functionalized with linear alkyl side chains, was found to exhibit excellent stability against hot concentrated NaOH solutions and Grignard reagents.
- Raiguel, Stijn,Thomas, Joice,Binnemans, Koen,Dehaen, Wim
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supporting information
p. 4850 - 4856
(2018/09/06)
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- Chemoselective Rapid Azo-Coupling Reaction for Bioconjugation
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Novel biomolecular conjugates containing non-natural aromatic chemical moieties covalently coupled to a diazonium compound and methods of their use are disclosed.
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Paragraph 0084
(2019/01/04)
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- Investigation of Strain-Promoted Azide-Alkyne Cycloadditions in Aqueous Solutions by Capillary Electrophoresis
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The Cu-free 1,3-dipolar cycloaddition of cyclooctynes and azides is an up-and-coming method in bioorganic chemistry and other disciplines. However, broad application is still hampered by major drawbacks such as poor solubility of the reactants in aqueous media and low reaction rates. It is thus of high demand to devise a fast and user-friendly strategy for the optimization of reaction conditions and reagent design. We describe a capillary electrophoresis (CE) study of reaction kinetics in strain-promoted azide-alkyne cycloadditions (SPAAC) using substrates with acidic or basic functionalities. This study reveals that the pH value has a significant effect on reaction rates as a result of changes in the reactants' charge state via protonation or deprotonation, and the concomitant changes of electronic properties. This novel experimental setup also enables the study of even more challenging conditions such as reactions in micelles and we did indeed observe much faster SPAAC reactions in the presence of surfactants. Careful combination of the above-mentioned parameters resulted in the identification of conditions enabling remarkable rate enhancement by a factor of 80. This electrophoretic method may thus serve as a versatile, fast and reliable tool for screening purposes in all research areas applying SPAAC reactions.
- Steflova, Jana,Storch, Golo,Wiesner, Sarah,Stockinger, Skrollan,Berg, Regina,Trapp, Oliver
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supporting information
p. 604 - 613
(2018/01/27)
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- Comprehensive Synthesis of Amino Acid-Derived Thiazole Peptidomimetic Analogues to Understand the Enigmatic Drug/Substrate-Binding Site of P-Glycoprotein
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A novel set of 64 analogues based on our lead compound 1 was designed and synthesized with an initial objective of understanding the structural requirements of ligands binding to a highly perplexing substrate-binding site of P-glycoprotein (P-gp) and their effect on modulating the ATPase function of the efflux pump. Compound 1, a stimulator of P-gp ATPase activity, was transformed to ATPase inhibitory compounds 39, 53, and 109. The ATPase inhibition by these compounds was predominantly contributed by the presence of a cyclohexyl group in lieu of the 2-aminobenzophenone moiety of 1. The 4,4-difluorocyclohexyl analogues, 53 and 109, inhibited the photolabeling by [125I]-IAAP, with IC50 values of 0.1 and 0.76 μM, respectively. Selected compounds were shown to reverse paclitaxel resistance in HEK293 cells overexpressing P-gp and were selective toward P-gp over CYP3A4. Induced-fit docking highlighted a plausible binding pattern of inhibitory compounds in the putative-binding pocket of P-gp. The current study underscores the stringent requirement by P-gp to bind to chemically similar molecules.
- Patel, Bhargav A.,Abel, Biebele,Barbuti, Anna Maria,Velagapudi, Uday Kiran,Chen, Zhe-Sheng,Ambudkar, Suresh V.,Talele, Tanaji T.
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p. 834 - 864
(2018/02/17)
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- Stable Lanthanide-Organic Framework Materials Constructed by a Triazolyl Carboxylate Ligand: Multifunction Detection and White Luminescence Tuning
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Under hydrothermal conditions, we have successfully synthesized six isostructural lanthanide coordination polymers, [LnL1.5(H2O)2]·1.75H2O (1-6; Ln = Eu, La, Pr, Nd, Sm, Gd), by the reaction of 5-methyl-1-(4-carboxylphenyl)-1H-1,2,3-triazole-4-carboxylic acid (H2L) and Ln(NO3)3·6H2O. Structural analysis shows that polymers 1-6 show novel three-dimensional supramolecular network structures. The luminescent properties for polymer 1 have been investigated at room temperature. The results have shown that polymer 1 can be used as a chemical sensor for multifunctional testing such as UO22+, Fe3+ ion detection, and small organic molecule detection because of its strong fluorescence properties. In particular, polymer 1 exhibits extremely high selectivity and sensitivity for the detection of Fe3+ ions. In addition, white-light emission is achieved through a reasonable tuning proportion by mixing Gd3+ and Eu3+.
- Wang, Yu,Xing, Shang-Hua,Bai, Feng-Ying,Xing, Yong-Heng,Sun, Li-Xian
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p. 12850 - 12859
(2018/10/15)
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- 1,2,3-Triazole-quinazolin-4(3H)-one conjugates: evolution of ergosterol inhibitor as anticandidal agent
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The present study describes the synthesis of 1,2,3-triazole-quinazolinone conjugates (5a-q) from ethyl 4-oxo-3-(prop-2-ynyl)-3,4-dihydroquinazoline-2-carboxylate and phenyl azide/substituted phenyl azides employing Cu(i) catalysed Huisgen 1,3-dipolar cycloaddition. The corresponding acids (6a-q) were obtained by hydrolysis of esters (5a-q) to study the effect of these functionalities on the biological activity. All synthesized compounds were screened for in vitro anticandidal evaluation against Candia albicans, Candida glabrata and Candida tropicalis strains. The results indicated that compound 5n showed potent anticandidal activity with IC50 in the range of 8.4 to 14.6 μg mL?1. Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed the non-toxic nature of the selected compounds. Growth kinetic study with compound 5n showed its fungicidal nature as no significant growth of Candida cells was observed even after 24 h. Cellular ergosterol content was determined in the presence of different concentrations of 5n to measure the activity of lanosterol 14α-demethylase indirectly. The results showed significant disruption of the ergosterol biosynthetic pathway through inhibition of lanosterol 14α-demethylase activity supported by docking studies (PDB: 5v5z). Overall, this study demonstrates the anticandidal potential of 5n which can serve as the lead for further structural optimization and SAR studies.
- Masood, Mir Mohammad,Irfan, Mohammad,Khan, Parvez,Alajmi, Mohamed F.,Hussain, Afzal,Garrison, Jered,Rehman, Md. Tabish,Abid, Mohammad
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p. 39611 - 39625
(2018/12/13)
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- CHEMOSELECTIVE THIOL-CONJUGATION WITH ALKENE OR ALKYNE-PHOSPHONAMIDATES
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Disclosed are novel conjugates and processes for the preparation thereof. A process for the preparation of alkene- or alkyne-phosphonamidates comprises the steps of (I) reacting a compound of formula (III), with an azide of formula (IV), to prepare a compound of formula (V), reacting a compound of formula (V) with a thiol-containing molecule of formula (VI), resulting in a compound of formula (VII).
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Page/Page column 89; 90
(2018/03/25)
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- Light-driven reversible surface functionalization with anthracenes: visible light writing and mild UV erasing
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We introduce a methodology to reversibly pattern planar surfaces via the light-induced dimerization of anthracenes, particularly involving a 9-triazolylanthracene motif. Specifically, we demonstrate that the visible light-induced forward reaction can be employed to pattern small molecule species as well as polymers in a spatially resolved fashion. Under UV irradiation, the generated patterns can be erased to regenerate reactive areas, which are then available for a new functionalization step. The dynamic change in surface chemistry is evidenced by ToF-SIMS.
- Claus, Tanja K.,Telitel, Siham,Welle, Alexander,Bastmeyer, Martin,Vogt, Andrew P.,Delaittre, Guillaume,Barner-Kowollik, Christopher
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supporting information
p. 1599 - 1602
(2017/02/10)
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- A Chemoselective Rapid Azo-Coupling Reaction (CRACR) for Unclickable Bioconjugation
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Chemoselective modification of complex biomolecules has become a cornerstone of chemical biology. Despite the exciting developments of the past two decades, the demand for new chemoselective reactions with unique abilities, and those compatible with existing chemistries for concurrent multisite-directed labeling, remains high. Here we show that 5-hydroxyindoles exhibit remarkably high reactivity toward aromatic diazonium ions and this reaction can be used to chemoselectively label proteins. We have previously genetically encoded the noncanonical amino acid 5-hydroxytryptophan in both E. coli and eukaryotes, enabling efficient site-specific incorporation of 5-hydroxyindole into virtually any protein. The 5-hydroxytryptophan residue was shown to allow rapid, chemoselective protein modification using the azo-coupling reaction, and the utility of this bioconjugation strategy was further illustrated by generating a functional antibody-fluorophore conjugate. Although the resulting azo-linkage is otherwise stable, we show that it can be efficiently cleaved upon treatment with dithionite. Our work establishes a unique chemoselective "unclickable" bioconjugation strategy to site-specifically modify proteins expressed in both bacteria and eukaryotes.
- Addy, Partha Sarathi,Erickson, Sarah B.,Italia, James S.,Chatterjee, Abhishek
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supporting information
p. 11670 - 11673
(2017/09/07)
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- Benzoic acid derivatives with trypanocidal activity: Enzymatic analysis and molecular docking studies toward trans-sialidase
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Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (14, 18, and 19) sharing a para-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC50) was 0.15 μM on the NINOA strain, and LC50 0.22 μM on the INC-5 strain. Additionally, compound 18 showed a moderate inhibition (47%) on the trans-sialidase enzyme and a binding model similar to DANA (pattern A).
- Kashif, Muhammad,Moreno-Herrera, Antonio,Villalobos-Rocha, Juan Carlos,Nogueda-Torres, Benjamín,Pérez-Villanueva, Jaime,Rodríguez-Villar, Karen,Medina-Franco, José Luis,De Andrade, Peterson,Carvalho, Ivone,Rivera, Gildardo
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- BROAD SPECTRUM ANTIVIRAL COMPOUNDS AND USES THEREOF
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Disclosed herein, inter alia, are agents having antiviral activity and methods of use thereof.
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Paragraph 0419-0421
(2017/03/21)
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- Glucose promoted facile reduction of azides to amines under aqueous alkaline conditions
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A quick and efficient method for the reduction of azides to amines in water using d-glucose and KOH as green reagents is reported. The protocol is simple, inexpensive, scalable, and can be applied to different aromatic, heteroaromatic and sulphonyl azides. A high level of chemoselectivity is observed for azide reduction in the presence of other reducible functionalities like cyano, nitro, ether, ketone, amide and acid. The reaction gets completed in a short time (5-20 minutes), and furnishes the amines in high yield (85-99%). Unlike conventional hydrogenations, this reduction protocol does not require any metal catalyst, elaborate experimental setup or use of high-pressure equipment.
- Chandna, Nisha,Kaur, Fatehjeet,Kumar, Shobhna,Jain, Nidhi
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supporting information
p. 4268 - 4271
(2017/09/29)
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- Design, Synthesis, and Biological Evaluation of New Peptide Analogues as Selective COX-2 Inhibitors
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A new class of peptide derivatives possessing SO2Me and N3 pharmacophores at the para position of a phenyl ring bound to different aromatic amino acids were synthesized based on solid-phase synthesis methodology, and evaluated as selective cyclooxygenase-2 (COX-2) inhibitors. One of the analogues, i.e., compound 2a as the representative of this series, was recognized as the highest selective COX-2 inhibitor with a COX-2 selectivity index of >500. The structure–activity relationships (SARs) acquired indicated that compound 2a containing a 4-(methylsulfonyl)benzoyl group as a pharmacophore and tyrosine as a ring bearing amino acid in the second position and glutamic acid as the C-terminal amino acid can give the essential geometry to provide selective COX-2 inhibitory activity. Antiproliferative activity of the synthesized peptides (1a–7b) was also determined against four different human cancer cell lines, including MCF-7, HepG2, A549, and HeLa. According to our results, A549, HepG2, and MCF7 seemed to be more sensitive cell lines than HeLa cells encountering these compounds, which gave inhibitory action with IC50 values from 4.8 to 64.4 μM. In this regard, compounds 3a and 2b displayed the best inhibitory activity against the cell lines. Moreover, a good correlation was observed between the antiproliferative potency and the COX-2 inhibitory activity of compounds 1a, 2a, 2b, and 5b. Such findings suggest that one of the mechanism of anticancer activity of these peptides may be through the COX-2 inhibitory action.
- Ahmaditaba, Mohammad A.,Shahosseini, Soraya,Daraei, Bahram,Zarghi, Afshin,Houshdar Tehrani, Mohammad H.
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- Ribosome Rescue Inhibitors Kill Actively Growing and Nonreplicating Persister Mycobacterium tuberculosis Cells
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The emergence of Mycobacterium tuberculosis (MTB) strains that are resistant to most or all available antibiotics has created a severe problem for treating tuberculosis and has spurred a quest for new antibiotic targets. Here, we demonstrate that trans-translation is essential for growth of MTB and is a viable target for development of antituberculosis drugs. We also show that an inhibitor of trans-translation, KKL-35, is bactericidal against MTB under both aerobic and anoxic conditions. Biochemical experiments show that this compound targets helix 89 of the 23S rRNA. In silico molecular docking predicts a binding pocket for KKL-35 adjacent to the peptidyl-transfer center in a region not targeted by conventional antibiotics. Computational solvent mapping suggests that this pocket is a druggable hot spot for small molecule binding. Collectively, our findings reveal a new target for antituberculosis drug development and provide critical insight on the mechanism of antibacterial action for KKL-35 and related 1,3,4-oxadiazole benzamides.
- Alumasa, John N.,Manzanillo, Paolo S.,Peterson, Nicholas D.,Lundrigan, Tricia,Baughn, Anthony D.,Cox, Jeffery S.,Keiler, Kenneth C.
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p. 634 - 644
(2017/09/18)
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- Hydrotrope promoted in situ azidonation followed by copper catalyzed regioselective synthesis of β-hydroxytriazoles
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Abstract: The rapid method for the synthesis of organic azides was achieved by employing azide acceptors such as halides, epoxides and pseudohalides like diazonium salts and aryl boronic acids in hydrotropic media. In extension, the sequential multicomponent reaction of epoxides, azide and alkynes using copper catalysis has been discussed. The reaction proceeds via the in situ generation of azido-alcohol followed by synthesis of chiral β-hydroxytriazoles. This [3?+?2] cycloaddition reaction of azide and alkyne using copper catalysis serves as a green and efficient protocol in “Click Chemistry”. The nucleophilic addition of azide to epoxide and alkyne-azide cycloaddition is the two simultaneous regioselective click reactions observed in the proposed method. Graphical Abstract: [Figure not available: see fulltext.].
- Patil, Amol,Salunkhe, Rajashri
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p. 4175 - 4187
(2017/06/20)
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- One-Pot, Metal-Free Conversion of Anilines to Aryl Bromides and Iodides
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A metal-free synthesis of aryl bromides and iodides from anilines via halogen abstraction from bromotrichloromethane and diiodomethane is described. This one-pot reaction affords aryl halides from the corresponding anilines in moderate to excellent yields without isolation of diazonium salts. The transformation has short reaction times, a simple workup, and insensitivity to moisture and air and avoids excess halogenation. DFT calculations support a SRN1 mechanism. This method represents a convenient alternative to the classic Sandmeyer reaction.
- Leas, Derek A.,Dong, Yuxiang,Vennerstrom, Jonathan L.,Stack, Douglas E.
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supporting information
p. 2518 - 2521
(2017/05/24)
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- Neutral iodotriazole foldamers as tetradentate halogen bonding anion receptors
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Neutral tetradentate halogen bond donor foldamers were synthesised and exhibit enhanced anion affinities over their hydrogen bonding analogues, displaying iodide selectivity over lighter halide, carboxylate and dihydrogen phosphate anions. A foldamer with a chiral (S)-binaphthol motif was demonstrated to distinguish between enantiomers of chiral anions.
- Borissov, Arseni,Lim, Jason Y. C.,Brown, Asha,Christensen, Kirsten E.,Thompson, Amber L.,Smith, Martin D.,Beer, Paul D.
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supporting information
p. 2483 - 2486
(2017/03/01)
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- Antitumor compound and preparation method thereof
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The present invention is an antitumor compound belonging to the field of medicines, and particularly relates to an antitumor-active compound with a specific chemical structure and a preparation method and use of the antitumor-active compound. The antitumor-active compound is as shown in a general formula, wherein n is an integer from 0 to 3, R1 is methyl, fluorine, chlorine, bromine, carboxyl and a methyl ester, an ethyl ester, a propyl ester, an isopropyl ester, a n-butyl ester, an iso-butyl ester and a tert-butyl ester, R2 is acetyl, propionyl, benzoyl, and an alkyl group having 1-5 carbon atoms, X is CH2 or CO (carbonyl); positions of substituents on the aromatic ring may be 2-site-substituted, 3-site-substituted and 4-site-substituted, and the substitution may be mono-substituted and poly-substituted. The present invention provides the preparation method of the antitumor-active compound. Experiments show that the antitumor-active compound as a new-structure-type topoisomerase inhibitor plays a good role in inhibition of tumor activity.
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Paragraph 0065; 0066; 0094
(2016/10/09)
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- POLYCYCLIC EPOXIDES AND COMPOSITIONS THEREOF WITH ANTI-CANCER ACTIVITIES
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The present technology provides polycyclic epoxides of Formula I, compositions comprising such expoxides and methods of using such epoxides. In particular, these compounds are useful for inhibiting cancer cell proliferation and tumor angiogenesis or treating ovarian, breast, prostate, liver, pancreatic, and colon cancers, as well as leukemia.
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Paragraph 0309; 0310; 0313
(2016/12/01)
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- Design and synthesis of peptide conjugates of phosphoramide mustard as prodrugs activated by prostate-specific antigen
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A series of Glutaryl-Hyp-Ala-Ser-Chg-Gln-4-aminobenzyl phosphoramide mustard conjugates (1a-e) was designed and synthesized as potential prodrugs for site-specific activation by PSA in prostate cancer cells. All conjugates were found to be substrates of PSA with cleavage occurring between Gln and the para-aminobenzyl (PAB) linker. Structure-activity relationship studies on these conjugates indicated that introduction of electron-withdrawing fluorine(s) on the phenyl ring in the PAB linker uniformly improved the chemical stability of the conjugates while the position of substitution affected differently the self-immolative process of conjugates upon proteolysis. Introduction of a fluorine at ortho position to benzylic phosphoramide as in 1b results in better stability of the conjugate prior to activation while maintaining its antiproliferative activity upon activation by PSA. The conjugate 1b with 2-fluoro substitution was identified as a promising lead for further evaluation and optimization in the development of prostate cancer-targeted prodrugs.
- Wu, Xinghua,Hu, Longqin
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p. 2697 - 2706
(2016/06/08)
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- A comparison of novel organoiridium(III) complexes and their ligands as a potential treatment for prostate cancer
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A range of 1,4-substituted 2-pyridyl-N-phenyl triazoles were synthesised and evaluated for their antiproliferative properties against lymph node cancer of the prostate (LNCaP) and bone metastasis of prostate cancer (PC-3) cells. Excellent-to-low IC50 values were determined (5.6-250 μM), and a representative group of 4 ligands were then complexed to iridium(III) giving highly luminescent species. Reevaluation of these compounds against both cell lines was then undertaken and improved potency (up to 72-fold) was observed, giving IC50 values of 0.36-11 μM for LNCaP and 0.85-5.9 μM for PC-3. Preliminary screens for in vivo toxicity were conducted using a zebrafish model showing a wide range of induced toxicity depending of the compound evaluated. Apoptosis and Caspase-3 levels were also determined and showed no statistical difference between some of the treated specimens and the controls. This study may identify novel therapeutic agents for advanced stage of prostate cancer in humans.
- Hockey, Samantha C.,Barbante, Gregory J.,Francis, Paul S.,Altimari, Jarrad M.,Yoganantharajah, Prusothman,Gibert, Yann,Henderson, Luke C.
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p. 305 - 313
(2016/01/28)
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- Cu-Click Compatible Triazabutadienes to Expand the Scope of Aryl Diazonium Ion Chemistry
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Triazabutadienes can be used to readily generate reactive aryl diazonium ions under mild, physiologically relevant conditions. These conditions are compatible with a range of functionalities that do not tolerate traditional aryl diazonium ion generation. To increase the utility of this aryl diazonium ion releasing chemistry an alkyne-containing triazabutadiene was synthesized. The copper-catalyzed azide-alkyne cycloaddition ("Cu-click") reaction was utilized to modify the alkyne-containing triazabutadiene and shown to be compatible with the nitrogen-rich triazabutadiene. One of the triazole products was tethered to a fluorophore, thus enabling the direct fluorescent labeling of a model protein.
- Cornali, Brandon M.,Kimani, Flora W.,Jewett, John C.
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supporting information
p. 4948 - 4950
(2016/10/18)
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- Design of photoaffinity labeling probes derived from 3,4,5-trimethylfuran-2(5H)-one for mode of action elucidation
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Herein we report the synthesis of new probes for photoaffinity labeling with the aim of receptor identification and mode of action elucidation of 3,4,5-trimethylfuran-2(5H)-one (TMB), recently identified in the smoke of burning vegetation as an efficient seed germination inhibitor. These photoaffinity probes consist of an ethynyl group that acts as a tag for introduction of an optional detectable marker unit by an appropriate chemoselective ligation method after the photo-cross-linking operation.
- Po?ta, Martin,Soós, Vilmos,Beier, Petr
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p. 3809 - 3817
(2016/07/06)
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- 7-Aryl-triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrase IX and XII
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Sulfocoumarins behave as interesting inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Here, we report a new series of 7-substituted derivatives which were obtained by the click chemistry approach from 7-propargyloxy-sulfocoumarin and aryl azides incorporating halogens, hydroxy, methoxy and carboxyl moieties in their molecules. The new compounds were screened for the inhibition on four physiologically relevant human CA (hCA) isoforms, the cytosolic hCA I and II and the transmembrane tumor-associated hCA IX and XII. The new compounds did not inhibit the cytosolic isoforms but were low nanomolar inhibitors of the tumor-associated ones hCA IX and XII.
- Nocentini, Alessio,Ceruso, Mariangela,Carta, Fabrizio,Supuran, Claudiu T.
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p. 1226 - 1233
(2016/10/09)
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- Synthesis and in vitro cytotoxic evaluation of new triazole derivatives based on artemisinin via click chemistry
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The paper presents the synthesis of new artemisinin triazole derivatives via click chemistry and their in vitro cytotoxic evaluation against four cancer cell lines including MCF-7, LU-1, HL-60 and P388. The bioassay result showed that most of the target compounds were active against four cell lines, in which compounds 11g displayed the most potent inhibitory activity against HL-60 cell line with IC50 value of 2.5 μM.
- Binh, Le Huy,Van, Nguyen Thi Thuy,Kien, Vu Tuan,My, Nguyen Thi Thuy,Van Chinh, Luu,Nga, Nguyen Thi,Tien, Hoang Xuan,Thao, Do Thi,Vu, Tran Khac
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p. 738 - 750
(2016/03/08)
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- Reagents and methods for sirtuin capture
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The invention provides a method of preparing a sirtuin complex, a method for detecting a sirtuin in a sample, and a method of screening for compounds which inhibit the deacetylase activity of a sirtuin. The method includes (a) providing a sirtuin substrate having the formula: (b) providing NAD+ or an NAD+ analog having the formula: and (c) providing a sirtuin, wherein R1-R4, A1, A2, and n are as defined herein.
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- Synthesis, characterization, and antimicrobial activity of novel (E)-1-(aryl)-3-{3, 5-dimethoxy-4-[(1-(aryl)-1H-1,2,3-triazol-4-yl)methoxy]phenyl}prop-2-en-1-ones
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The new chalcone derivatives containing the 1,2,3-triazole ring system, namely, (E)-1-(aryl)-3-{3,5-dimethoxy-4-[(1-(aryl)-1H-1,2,3-triazol-4-yl)methoxy]phenyl}prop-2-en-1-ones, were synthesized in 65–88% yield by the “click chemistry” reactions of substituted acetophenones, 4-hydroxy-3,5-dimethoxy-benzaldehyde, and different substituted azides. The structure of the compounds was determined by the FT-IR, 1H NMR, 13C NMR, and mass spectroscopic analyses. Compounds 6a–6l were screened for in vitro antimicrobial activity by the agar disc diffusion method.
- Subhashini,Sravanthi, Ch.,Sravanthi,Shivaraj
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p. 1405 - 1411
(2016/08/12)
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