- New series of double-modified colchicine derivatives: Synthesis, cytotoxic effect and molecular docking
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Colchicine is a well-known anticancer compound showing antimitotic effect on cells. Its high cytotoxic activity against different cancer cell lines has been demonstrated many times. In this paper we report the syntheses and spectroscopic analyses of novel colchicine derivatives obtained by structural modifications at C7 (carbon-nitrogen single bond) and C10 (methylamino group) positions. All the obtained compounds have been tested in vitro to determine their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX, and BALB/3T3 cell lines. The majority of obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin and cisplatin against the tested cancerous cell lines. Additionally, most of the presented derivatives were able to overcome the resistance of LoVo/DX cells. Additionally, their mode of binding to β-tubulin was evaluated in silico. Molecular docking studies showed that apart from the initial amides 1 and 2, compound 14, which had the best antiproliferative activity (IC50 = 0.1–1.6 nM), stood out also in terms of its predicted binding energy and probably binds best into the active site of βI-tubulin isotype.
- Aminpour, Maral,Huczyn?ski, Adam,Krzywik, Julia,Maj, Ewa,Mozga, Witold,Tuszyn?ski, Jack A.,Wietrzyk, Joanna
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- ANTIMICROBIAL COMPOSITIONS, METHODS OF MAKING, AND METHODS OF USE
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The invention provides a protected antimicrobial compound and methods of using the same.
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Paragraph 0011; 0013
(2019/03/08)
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- Acid-Triggered, Acid-Generating, and Self-Amplifying Degradable Polymers
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We describe the 3-iodopropyl acetal moiety as a simple cleavable unit that undergoes acid catalyzed hydrolysis to liberate HI (pKa-10) and acrolein stoichiometrically. Integrating this unit into linear and network polymers gives a class of macromolecules that undergo a new mechanism of degradation with an acid amplified, sigmoidal rate. This trigger-responsive self-amplified degradable polymer undergoes accelerated rate of degradation and agent release.
- Miller, Kali A.,Morado, Ephraim G.,Samanta, Shampa R.,Walker, Brittany A.,Nelson, Arif Z.,Sen, Samya,Tran, Dung T.,Whitaker, Daniel J.,Ewoldt, Randy H.,Braun, Paul V.,Zimmerman, Steven C.
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supporting information
p. 2838 - 2842
(2019/03/05)
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- PROTECTED CARBOXYLIC ACID-BASED METABOLITES FOR THE TREATMENT OF MITOCHONDRIAL DISORDERS
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The present invention provides novel cell-permeable carboxylic acid-based metabolites and cell permeable precursors thereof aimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates fr
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Page/Page column 50
(2017/07/29)
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- METHOD FOR THE CATALYTIC REDUCTION OF ACID CHLORIDES AND IMIDOYL CHLORIDES
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The present application relates to methods for the catalytic reduction of acid chlorides and/or imidoyl chlorides. The methods comprise reacting the acid chloride or imidoyl chloride with a silane reducing agent in the presence of a catalyst such as [Cp(Pri3P)Ru(NCMe)2]+[PF6]?.
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Paragraph 0104
(2014/08/19)
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- Chemoselective ruthenium-catalyzed reduction of acid chlorides to aldehydes with dimethylphenylsilane
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A variety of aromatic and alkyl acid chlorides can be selectively converted into aldehydes using dimethylphenyl silane (HSiMe2Ph) as the reducing reagent in the presence of the cationic ruthenium catalyst {Cp[(i-Pr)3P]Ru(NCMe)2}+ [PF6] -. The reactions proceed under very mild conditions and are tolerant to many functional groups. Copyright
- Gutsulyak, Dmitry V.,Nikonov, Georgii I.
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experimental part
p. 607 - 611
(2012/04/23)
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- Intermolecular oxonium ylide mediated synthesis of medium-sized oxacycles
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Detailed in this account are our efforts toward efficient oxacycle syntheses. Two complementary approaches are discussed, with both employing chemoselective allyl ether activation and rearrangement as the key step. Vinyl substituted oxiranes and oxetanes provide a single step access to dihydropyrans and tetrahydrooxepines. Oxiranes proved to be poor substrates, while oxetanes were slightly better. An alternative approach using substituted allyl ethers proved successful and addressed the limitations encountered in the ring expansions.
- MacK, Daniel J.,Batory, Lindsay A.,Njardarson, Jon T.
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supporting information; experimental part
p. 378 - 381
(2012/03/09)
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- Amido macrolides
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Various macrolide compounds such as those having the following formulas are provided where the variables have the values provided herein.
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- Amido macrolides
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Various macrolide compounds such as those having the following formulas are provided where the variables have the values provided herein.
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Page/Page column 25
(2010/01/31)
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- N-(4-methylbenzenesulfonyl)- pyrrolidines and piperidines by a tandem S(N)2-Michael addition reaction
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A tandem S(N)2-Michael addition sequence has been developed for the preparation of N-(4-methylbenzenesulfonyl)- pyrrolidines and piperidines bearing functionalized side chains at C-2.
- Bunce, Richard A.,Allison, Jeffrey C.
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p. 2175 - 2186
(2007/10/03)
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- 24-and 25-substituted avermectin and milbemycin derivatives
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Novel avermectin and milbemycin derivatives are disclosed, where the C-24 and C-25 carbon atoms are substituted by hydrogen, alkyl, alkenyl, substituted alkyl or substituted alkenyl groups. These compounds can be further substituted at the 4"-, 5-, 13-, and 23-positions. The new C-24 and C-25 substituted avermect prepared by cleavage of known and suitably protected avermectin and milbemycin compounds. The new compounds are potent anti-parasitic agents, in particular, the compounds are anthelmintic, insecticidal and acaricidal agents.
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- Oxidation of Isopropylcyclopropane by Chromyl Chloride: Ring-Opened Products Support a Hydrogen Atom Abstraction Mechanism
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Chromyl chloride (CrO2Cl2) reacts with neat isopropylcyclopropane at 65 °C to give a dark precipitate along with at least 20 organic products. Both cyclopropyl products and ring-opened products are observed: 2-cyclopropyl-2-chloropropane (1,0.4% yield based on chromium), 2-cyclopropyl-2-propanol (2, 0.2%), 5-chloro-2-methyl-2-pentene (3, 0.3%), and 4-methyl-3-penten-1-ol (4, 0.5%) as well as other ring-opened products. Authentic samples of 1-4 were synthesized, and their GC and GC/ MS data were compared with the reaction mixture. Other organic products (5-10) were tentatively assigned by GC/MS on the basis of their m / z and fragmentation patterns. The ratio of (1 + 2) vs (3 + 4) increases by a factor of 2 when the initial concentration of CrO2Cl2 increases from 0.3 to 1.12 M. The reaction was also carried out in the gas phase, and essentially all the products from the liquid phase reaction were observed. The products are explained by a mechanism involving initial hydrogen atom abstraction from the substrate. The resulting dimethylcyclopropylcarbinyl radical can either be trapped by CrO2Cl2 (to form 1 and 2) or ring-open to give 4-methyl-3-pentenyl radical, which reacts with CrO2Cl2 to form 3 and 4 as well as further oxidized products. The oxidation of isopropylcyclopropane by MnO4- in pyridine was also examined. Acetone, an expected ring-opened product, was the only product observed by our analytical techniques. Me2C18O is produced from 18O-labeled MnO4-. These results suggest that the reactions of CrO2Cl2 and MnO4- with isopropylcyclopropane proceed by hydrogen atom transfer to form organic radical intermediates.
- Wang, Kun,Mayer, James M.
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p. 4248 - 4252
(2007/10/03)
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- 4"-and 4'-alkylthio avermectin derivatives
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Avermectin derivatives are disclosed wherein the 4"-hydroxy group is replaced by a substituted alkylthio or acylthio group or an iodo group. These avermectin derivatives can be further derivatized at the 5- and 23-positions as ketoximes or O-substituted ketoximes. The 4"-substituted avermectin derivatives are prepared from the 4"- and 4'-trifluoromethanesulfonyl avermectin derivatives with halo- or sulfur-containing nucleophiles. The 4"- and 4'-α- and β-trifluoromethane sulfonates are prepared selectively and converted into 4"- or 4'-alkyl- or acylsulfides, or iodides using the appropriate sulfur-containing or iodine nucleophile. Substituted sulfoxy and sulfonyl substituents at the 4"- and 4'-positions are prepared from oxidation of the corresponding substituted sulfides. The new compounds are potent anti-parasitic agents; in particular, the compounds are anthelmintic, insecticidal and acaricidal agents.
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- SYNTHESIS OF SELENOACETALS
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This paper reports our results concerning the syntheses of various bis(alkylseleno)alkanes and some of their arylseleno analogues by different methods.The scope and limitation of each of them are presented.
- Clarembeau, M.,Cravador, A.,Dumont, W.,Hevesi, L,Krief, A.,et al.
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p. 4793 - 4812
(2007/10/02)
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- Volatile Flavor Components of Kogyoku Apples
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A steam distillate of Kogyoku apple juice was extracted with ethyl ether.The extract was separated into its acidic and neutral fractions, and the neutral fraction was further separated into five fractions by column chromatography.All these fractions were analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry.Several compounds in the neutral fraction of the juice were isolated by preparative GC, and then identified by comparing their mass, infrared and nuclear magnetic resonance spectra with those of authentic compounds.Sixty-seven compounds were identified form the juice, 22 compounds being found for the first time as apple flavor components.Among them, the following compounds have not been previously reported as flavor components in any natural product; (Z)-5-octen-1-ol, (Z,Z)- and (E,Z)-3,5-octadien-1-ols, (Z,Z)- and (E,Z)-3,5-octadien-1-yl acetates, (Z)-5-octene-1,3-diol and 3-hydroxy-(Z)-5-octen-1-yl acetate.We also made a comparison of the volatile flavor compounds in the juice and peel of the same apples.
- Yajima, Izumi,Yanai, Tetsuya,Nakamura, Mikio,Sakakibara, Hidemasa,Hayashi, Kazuo
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p. 849 - 856
(2007/10/02)
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- Synthesis of 2-Hydroxybut-3-enylglucosinolate (Progoitrin)
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A synthesis of 2-hydroxybut-3-enylglucosinolate (progoitrin) is described.Its properties and authentication of its biological activity are discussed.This is the first time that this particular glucosinolate has been isolated in pure form by synthesis.
- MacLeod, Alexander J.,Rossiter, John T.
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p. 717 - 721
(2007/10/02)
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