- Novel Copper-Containing Cytotoxic Agents Based on 2-Thioxoimidazolones
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A series of 73 ligands and 73 of their Cu+2 and Cu+1 copper complexes with different geometries, oxidation states of the metal, and redox activities were synthesized and characterized. The aim of the study was to establish the structure-activity relations
- Krasnovskaya, Olga O.,Guk, Dmitry A.,Naumov, Alexey E.,Nikitina, Vita N.,Semkina, Alevtina S.,Vlasova, Kseniya Yu.,Pokrovsky, Vadim,Ryabaya, Oksana O.,Karshieva, Saida S.,Skvortsov, Dmitry A.,Zhirkina, Irina V.,Shafikov, Radik R.,Gorelkin, Petr V.,Vaneev, Alexander N.,Erofeev, Alexander S.,Mazur, Dmitrii M.,Tafeenko, Viktor A.,Pergushov, Vladimir I.,Melnikov, Mikhail Ya.,Soldatov, Mikhail A.,Shapovalov, Victor V.,Soldatov, Alexander V.,Akasov, Roman. A.,Gerasimov, Vasily M.,Sakharov, Dmitry A.,Moiseeva, Anna A.,Zyk, Nikolay V.,Beloglazkina, Elena K.,Majouga, Alexander G.
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- Synthesis of isothiocyanates using DMT/NMM/TsO? as a new desulfurization reagent
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Thirty-three alkyl and aryl isothiocyanates, as well as isothiocyanate derivatives from esters of coded amino acids and from esters of unnatural amino acids (6-aminocaproic, 4-(aminomethyl)benzoic, and tranexamic acids), were synthesized with satisfactory or very good yields (25–97%). Synthesis was performed in a “one-pot”, two-step procedure, in the presence of organic base (Et3 N, DBU or NMM), and carbon disulfide via dithiocarbamates, with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO? ) as a desulfurization reagent. For the synthesis of aliphatic and aromatic isothiocyanates, reactions were carried out in a microwave reactor, and selected alkyl isothiocyanates were also synthesized in aqueous medium with high yields (72–96%). Isothiocyanate derivatives of L-and D-amino acid methyl esters were synthesized, under conditions without microwave radiation assistance, with low racemization (er 99 > 1), and their absolute configuration was confirmed by circular dichroism. Isothiocyanate derivatives of natural and unnatural amino acids were evaluated for antibacterial activity on E. coli and S. aureus bacterial strains, where the most active was ITC 9e.
- Janczewski, ?ukasz,Kolesińska, Beata,Kr?giel, Dorota
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- Systems biology approaches based discovery of a small molecule inhibitor targeting both c-Met/PARP-1 and inducing cell death in breast cancer
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Breast cancer is the second most common types of cancer worldwide. Molecular strategies have developed rapidly; however, novel treatments strategies with high efficacy and lower toxicity are still urgently demanded. Notably, biological networks estimated from microarray data and functional activity network analysis could be utilized to identify and validate potential targets. In this study, two microarray data (GSE13477, GSE31192) were firstly selected, and analyzed by multi-functional activity network analysis to generate the core protein-protein-interaction (PPI) network. Several potential targets were subsequently identified and c-Met and poly (ADP-ribose) polymerase-1 (PARP-1) were manually chosen as the key targets in breast cancer. Furthermore, virtual screening and molecular dynamics (MD) simulations were utilized to recognize novel c-Met/PARP-1 inhibitors in Specs products database. Three small molecules, namely, ZINC19909930, ZINC20032678 and ZINC13562414 were selected. Additionally, these compounds were synthesized, and two breast cancer cell lines, MDA-MB-231 and MCF-7 cells were used to validate our bioinformatic findings in vitro. MTT assay and Hoechst staining showed that ZINC20032678 significantly induced breast cancer cell death, which was mediated through apoptosis by flow cytometry. Furthermore, ZINC20032678 was shown to target the active sites of the both targets and recruitment of downstream apoptotic signaling pathways, eventually inducing breast cancer cell apoptosis. Collectively, our findings not only offer systems biology approaches based drug target identification, but also provide the new clues for developing novel inhibitors for future breast cancer research.
- Chen, Jie,Cheng, Lijia,Dong, Hongbo,He, Gang,Shi, Zheng,Tang, Yong,Xiong, Hang,Xu, Guangya,Yan, Xueling,Yu, Tian,Zhou, Hui
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p. 2656 - 2666
(2020/03/13)
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- Synthesis of Isothiocyanates and Unsymmetrical Thioureas with the Bench-Stable Solid Reagent (Me4N)SCF3
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A highly efficient, selective, and rapid transformation of primary amines and diamines to isothiocyanates and cyclic thioureas is disclosed. As opposed to established approaches that employ toxic or volatile electrophilic liquids and require reaction control (i.e., slow addition, cooling), this protocol utilizes the bench-stable, solid reagent (Me4N)SCF3 at room temperature. The method is characterized by operational simplicity, high speed, efficiency, high functional group tolerance, and late-stage applicability. The byproducts are solids, allowing isolation of the target compounds by filtration.
- Scattolin, Thomas,Klein, Alexander,Schoenebeck, Franziska
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supporting information
p. 1831 - 1833
(2017/04/11)
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- Direct synthesis of isothiocyanates from isonitriles by molybdenum-catalyzed sulfur transfer with elemental sulfur
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The direct molybdenum-catalyzed sulfuration of a variety of isonitriles with elemental sulfur or propene sulfide as sulfur donors affords the corresponding isothiocyanates in good yields and under mild reaction conditions. A catalytic cycle is suggested, in which the molybdenum oxo disulfur complex operates as the active sulfur-transferring species. A novel adduct between the isonitrile and the molybdenum complex has been characterized by X-ray analysis and its association constant determined by UV-vis spectroscopy, but this adduct appears not to be involved in the sulfur-transfer process.
- Adam, Waldemar,Bargon, Rainer M.,Bosio, Sara G.,Schenk, Wolfdieter A.,Stalke, Dietmar
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p. 7037 - 7041
(2007/10/03)
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- Activation of Dithiocarbamate by 2-Halothiazolium Salts
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Activation of dithiocarbamate salts with 2-halo-3-alkyl-4-phenylthiazolium salt and subsequent one-pot nucleophilic reaction with N, S, and O nucleophiles provided substituted thioureas, dithiocarbamates, and thiocarbamates or amides, respectively, under very mild conditions.A useful thiocarbonyl-transfer reaction is also described that consists of activation of imidazolodithiocarbamate and a subsequent one-pot nucleophilic reaction. (Thiocarbonyl)diimidazole is generated in situ.
- Sugimoto, Hirohiko,Makino, Itsuo,Hirai, Kentaro
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p. 2263 - 2267
(2007/10/02)
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- Substitution Reaction of Organic Halide by Trimethylsilyl Isothiocyanate: Formation of Thiocyanate and Its Rearrangement to Isothiocyanate
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The reaction of organic halide with trimethylsilyl isothiocyanate (TMSTC) gave thiocyanate 1 and its isomerized isothiocyanate 2.Details of the substitution and the isomerization reactions were examined.
- Nishiyama, Kozaburo,Oba, Makoto
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p. 2692 - 2694
(2007/10/02)
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