- Carboxyl Methyltransferase Catalysed Formation of Mono- and Dimethyl Esters under Aqueous Conditions: Application in Cascade Biocatalysis
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Carboxyl methyltransferase (CMT) enzymes catalyse the biomethylation of carboxylic acids under aqueous conditions and have potential for use in synthetic enzyme cascades. Herein we report that the enzyme FtpM from Aspergillus fumigatus can methylate a broad range of aromatic mono- and dicarboxylic acids in good to excellent conversions. The enzyme shows high regioselectivity on its natural substrate fumaryl-l-tyrosine, trans, trans-muconic acid and a number of the dicarboxylic acids tested. Dicarboxylic acids are generally better substrates than monocarboxylic acids, although some substituents are able to compensate for the absence of a second acid group. For dicarboxylic acids, the second methylation shows strong pH dependency with an optimum at pH 5.5–6. Potential for application in industrial biotechnology was demonstrated in a cascade for the production of a bioplastics precursor (FDME) from bioderived 5-hydroxymethylfurfural (HMF).
- Ashbrook, Chloe,Carnell, Andrew J.,Goulding, Ellie,Hatton, Harry,Johnson, James R.,Kershaw, Neil M.,McCue, Hannah V.,Rigden, Daniel J.,Ward, Lucy C.
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supporting information
(2022/02/21)
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- Development of Gene-Targeted Polypyridyl Triplex-Forming Oligonucleotide Hybrids
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In the field of nucleic acid therapy there is major interest in the development of libraries of DNA-reactive small molecules which are tethered to vectors that recognize and bind specific genes. This approach mimics enzymatic gene editors, such as ZFNs, TALENs and CRISPR-Cas, but overcomes the limitations imposed by the delivery of a large protein endonuclease which is required for DNA cleavage. Here, we introduce a chemistry-based DNA-cleavage system comprising an artificial metallo-nuclease (AMN) that oxidatively cuts DNA, and a triplex-forming oligonucleotide (TFO) that sequence-specifically recognises duplex DNA. The AMN-TFO hybrids coordinate CuII ions to form chimeric catalytic complexes that are programmable – based on the TFO sequence employed – to bind and cut specific DNA sequences. Use of the alkyne-azide cycloaddition click reaction allows scalable and high-throughput generation of hybrid libraries that can be tuned for specific reactivity and gene-of-interest knockout. As a first approach, we demonstrate targeted cleavage of purine-rich sequences, optimisation of the hybrid system to enhance stability, and discrimination between target and off-target sequences. Our results highlight the potential of this approach where the cutting unit, which mimics the endonuclease cleavage machinery, is directly bound to a TFO guide by click chemistry.
- Zuin Fantoni, Nicolò,McGorman, Bríonna,Molphy, Zara,Singleton, Daniel,Walsh, Sarah,El-Sagheer, Afaf H.,McKee, Vickie,Brown, Tom,Kellett, Andrew
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p. 3563 - 3574
(2020/10/02)
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- A cationic Zr-based metal organic framework with enhanced acidic resistance for selective and efficient removal of CrO42-
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Water pollution caused by CrO42- has become a global concern due to its high aqueous solubility and good mobility in the underground environment. Recently, water stable zirconium based metal-organic frameworks (Zr-MOFs) have been tested as adsorbents to remove pollutants from contaminated water. However, the low adsorption capacity of Zr-MOFs towards ionic pollutants is unsatisfactory due to their neutral nature. Herein, a cationic Zr-MOF (Zr-C-MOF) was obtained by directly introducing a pyridinium salt as a ligand with an impressive ion exchange capability. Zr-C-MOF demonstrated enhanced acidic resistance and selectively high adsorption of CrO42-. The characteristics of the obtained Zr-C-MOF were confirmed via various techniques including PXRD, FT-IR spectroscopy, 1H-NMR spectroscopy, TGA, SEM, EDX and XPS. Batch adsorption studies have been conducted to gain a deep understanding of the kinetics mechanism, pH effects, adsorption isotherm and the effects of other competing ions. The kinetics and adsorption isotherm of CrO42- adsorption onto Zr-C-MOF were found to well fit the pseudo-second-order rate equation and the Langmuir model, respectively. The comparison of FT-IR, PXRD, SEM, EDX and XPS results of the samples before and after CrO42- adsorption revealed the adsorption mechanism of the anion exchange process. This journal is
- Jiang, Chao,Sun, Ruopei,Du, Ziyao,Singh, Vikramjeet,Chen, Suwen
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p. 12646 - 12653
(2020/10/13)
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- Design, synthesis, and biological characterization of a new class of symmetrical polyamine-based small molecule CXCR4 antagonists
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CXCR4, a well-studied coreceptor of human immunodeficiency virus type 1 (HIV-1) entry, recognizes its cognate ligand SDF-1α (also named CXCL12) which plays many important roles, including regulating immune cells, controlling hematopoietic stem cells, and directing cancer cells migration. These pleiotropic roles make CXCR4 an attractive target to mitigate human disorders. Here a new class of symmetrical polyamines was designed and synthesized as potential small molecule CXCR4 antagonists. Among them, a representative compound 21 (namely HF50731) showed strong CXCR4 binding affinity (mean IC50 = 19.8 nM) in the CXCR4 competitive binding assay. Furthermore, compound 21 significantly inhibited SDF-1α-induced calcium mobilization and cell migration, and blocked HIV-1 infection via antagonizing CXCR4 coreceptor function. The structure-activity relationship analysis, site-directed mutagenesis, and molecular docking were conducted to further elucidate the binding mode of compound 21, suggesting that compound 21 could primarily occupy the minor subpocket of CXCR4 and partially bind in the major subpocket by interacting with residues W94, D97, D171, and E288. Our studies provide not only new insights for the fragment-based design of small molecule CXCR4 antagonists for clinical applications, but also a new and effective molecular probe for CXCR4-targeting biological studies.
- An, Jing,Fang, Xiong,Huang, Lina S.,Huang, Ziwei,Liang, Boqiang,Meng, Qian,Schooley, Robert T.,Wang, Juan,Xu, Yan,Zhang, Chaozai,Zhang, Huijun,Zhang, Xingquan,Zhu, Siyu
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supporting information
(2020/06/03)
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- New Water-Soluble Copper(II) Complexes with Morpholine-Thiosemicarbazone Hybrids: Insights into the Anticancer and Antibacterial Mode of Action
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Six morpholine-(iso)thiosemicarbazone hybrids HL1-HL6 and their Cu(II) complexes with good-to-moderate solubility and stability in water were synthesized and characterized. Cu(II) complexes [Cu(L1-6)Cl] (1-6) formed weak dimeric associates in the solid state, which did not remain intact in solution as evidenced by ESI-MS. The lead proligands and Cu(II) complexes displayed higher antiproliferative activity in cancer cells than triapine. In addition, complexes 2-5 were found to specifically inhibit the growth of Gram-positive bacteria Staphylococcus aureus with MIC50 values at 2-5 μg/mL. Insights into the processes controlling intracellular accumulation and mechanism of action were investigated for 2 and 5, including the role of ribonucleotide reductase (RNR) inhibition, endoplasmic reticulum stress induction, and regulation of other cancer signaling pathways. Their ability to moderately inhibit R2 RNR protein in the presence of dithiothreitol is likely related to Fe chelating properties of the proligands liberated upon reduction.
- Ohui, Kateryna,Afanasenko, Eleonora,Bacher, Felix,Ting, Rachel Lim Xue,Zafar, Ayesha,Blanco-Cabra, Núria,Torrents, Eduard,D?m?t?r, Orsolya,May, Nóra V.,Darvasiova, Denisa,Enyedy, éva A.,Popovi?-Bijeli?, Ana,Reynisson, Jóhannes,Rapta, Peter,Babak, Maria V.,Pastorin, Giorgia,Arion, Vladimir B.
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supporting information
p. 512 - 530
(2019/01/04)
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- MODULATORS OF ESTROGEN RECEPTOR PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a cereblon, Von Hippel-Lindau ligase-binding moiety, Inhibitors of Apotosis Proteins, or mouse double-minute homolog 2 ligand, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
- -
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Paragraph 00409
(2018/08/20)
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- A class of 2, 3 - dihydronaphth block pyrimidine analogs, its synthetic method, pharmaceutical composition and use thereof
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The invention belongs to the technical field of medicines and relates to a 2,3-dihydronaphthalene-embedded m-diazabenzene analogue represented as the following general formula I and a preparation method thereof. The 2,3-dihydronaphthalene-embedded m-diazabenzene analogue has a function of inhibiting biological activities of different subtypes of a protein-tyrosine-phosphatase family (PTPases), can be used as a tool compound for researching a biological function correlation of the subtypes of the protein-tyrosine-phosphatase family (PTPases) in a cell signal transduction process, and provides a new approach for preventing and treating cancer, metabolic and immunological diseases, angiocardiopathy and neurological diseases.
- -
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Paragraph 0234-0236
(2017/07/22)
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- INHIBITORS OF COLLAGEN PROLYL 4-HYDROXYLASE
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Biheteroaryl dicarboxylates and esters, and salts thereof which are useful as modulators of CP4H activity and more particularly as inhibitors of CP4H. Compounds of formula: and salts thereof where: X is S, O, NH, or NR, where R is an alkyl group having 1-3 carbon atoms; R1 and R2 independently are —OR7, or —NHSO2R8, where R7 is selected from: hydrogen, alkyl, alkenyl, alkoxyalkyl, —R′—CO—R″, —R′—CO—O—R″, —CO—R″, —R′—O—CO—R″, —R′—CO—NR″, —CO—NR″, or —R′—O—CO—NR″, and R8 is selected from hydrogen, alkyl, aryl, arylalkyl; R3, R4 and R6 independently are hydrogen, alkyl, alkoxy, alkenyl, alkenoxy, halo alkyl, haloalkenyl, halogen, hydroxyl, hydroxyalkyl, hydroxyalkenyl, aryl, aryloxy, arylalkyl or arylalkyloxy; R5 is hydrogen, halogen, alkyl having 1-3 carbon atoms, or alkoxy having 1-3 carbon atoms; —R′— is a divalent straight chain or branched alkylene, and —R″ is an alkyl, alkenyl, arylalkyl, or aryl group. Methods for inhibition of CP4H in vivo and in vitro.
- -
-
Paragraph 0309; 0310; 0311
(2016/10/17)
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- BTK INHIBITORS
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The present invention provides Bruton's Tyrosine Kinase (Btk) inhibitor compounds according to Formula (I), or pharmaceutically acceptable salts or stereoisomers thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of Btk inhibitor compounds of Formula (I) in the treatment of Btk mediated disorders.
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Page/Page column 58
(2016/08/03)
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- 1H-2,3-Dihydroperimidine derivatives: A new class of potent protein Tyrosine Phosphatase 1B inhibitors
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A series of 1H-2,3-dihydroperimidine derivatives was designed, synthesized, and evaluated as a new class of inhibitors of protein tyrosine phosphatase 1B (PTP1B) with IC50 values in the micromolar range. Compounds 46 and 49 showed submicromolar inhibitory activity against PTP1B, and good selectivity (3.48-fold and 2.10-fold respectively) over T-cell protein tyrosine phosphatases (TCPTP). These results have provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.
- Wang, Wen-Long,Yang, Dong-Lin,Gao, Li-Xin,Tang, Chun-Lan,Ma, Wei-Ping,Ye, Hui-Hua,Zhang, Si-Qi,Zhao, Ya-Nan,Xu, Hao-Jie,Hu, Zhao,Chen, Xia,Fan, Wen-Hua,Chen, Hai-Jun,Li, Jing-Ya,Nan, Fa-Jun,Li, Jia,Feng, Bainian
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p. 102 - 121
(2014/02/14)
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- Primary coloured electrochromism of aromatic oxygen and sulfur diesters
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Eleven aromatic diesters and thioic S,S′-diesters were synthesized and investigated using electrochemical (cyclic voltammetry and controlled potential electrolysis) and UV-vis spectroscopic techniques over a range of temperatures. Nine of the compounds exhibited vibrant colour changes from a colourless state in their neutral forms to brightly coloured upon one-electron electrochemical reduction in acetonitrile. The compounds were found to display either red, green or blue colours in their one-electron reduced states. The electrochromic properties of 3 of the compounds that displayed the most vibrant colour changes were examined in solution using a gold micro-mesh electrode laminated inside a polymer film.
- Xu, Xiuhui,Webster, Richard D.
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p. 18100 - 18107
(2014/05/20)
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- Synthesis of planar chiral N-heterocyclic-substituted pyridinophanes
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Four new planar chiral N-heterocyclic-substituted [2](1,4)benzene[2](2,5) pyridinophanes have been synthesized. With the attached pyrazole, triazole, tetrazole, and pyrimidine moieties, different N,N-chelating ligands that vary in the number of enclosed nitrogen atoms, ring size, and electronic properties were added to a mostly neglected class of pyridinophanes. Additionally, the known synthesis of the pyridinophane scaffold was simplified considerably. With the acetyl, amino, and amido pyridinophane, various useful intermediates for new pyridinophane ligands were synthesized, which would allow for further investigations of this ligand system. New planar chiral bis(heterocyclic) N-donors based on the rarely investigated class of [2](1,4)-benzene[2](2,5) pyridinophanes were synthesized. The synthesis of the pyridinophane scaffold was simplified, and a pyrazole, triazole, tetrazole, and pyrimidine heterocycle were successfully attached to the planar chiral backbone. Copyright
- Kramer, Joshua J. P.,Nieger, Martin,Braese, Stefan
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supporting information
p. 541 - 549
(2013/02/26)
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- Molecular docking and enzymatic evaluation to identify selective inhibitors of aspartate semialdehyde dehydrogenase
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Microbes that have gained resistance against antibiotics pose a major emerging threat to human health. New targets must be identified that will guide the development of new classes of antibiotics. The selective inhibition of key microbial enzymes that are responsible for the biosynthesis of essential metabolites can be an effective way to counter this growing threat. Aspartate semialdehyde dehydrogenases (ASADHs) produce an early branch point metabolite in a microbial biosynthetic pathway for essential amino acids and for quorum sensing molecules. In this study, molecular modeling and docking studies were performed to achieve two key objectives that are important for the identification of new selective inhibitors of ASADH. First, virtual screening of a small library of compounds was used to identify new core structures that could serve as potential inhibitors of the ASADHs. Compounds have been identified from diverse chemical classes that are predicted to bind to ASADH with high affinity. Next, molecular docking studies were used to prioritize analogs within each class for synthesis and testing against representative bacterial forms of ASADH from Streptococcus pneumoniae and Vibrio cholerae. These studies have led to new micromolar inhibitors of ASADH, demonstrating the utility of this molecular modeling and docking approach for the identification of new classes of potential enzyme inhibitors.
- Luniwal, Amarjit,Wang, Lin,Pavlovsky, Alexander,Erhardt, Paul W.,Viola, Ronald E.
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experimental part
p. 2950 - 2956
(2012/06/29)
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- Enantioselective Fujiwara-Moritani indole and pyrrole annulations catalyzed by chiral palladium(II)-NicOx complexes
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The catalytic asymmetric Fujiwara-Moritani ring closures of several indole-and pyrrole-based cyclization precursors are reported. These unprecedented oxidative palladium(II)-catalyzed annulations allow for the formation of a stereogenic quaternary carbon atom, and decent levels of enantiocontrol are seen in 5-exo-trig cyclizations (54% ee for an indole and 76% ee for a pyrrole) while 6-exo-trig ring closures afford essentially racemic material. Novel oxazoline ligands with a nicotine platform (NicOx) are pivotal for good catalytic turnover as conventional PyOx ligands failed to produce acceptable chemical yields. The preparation of these NicOx ligands as well as the syntheses of the cyclization precursors are described in detail.
- Schiffner, Julia A.,Woeste, Thorsten H.,Oestreich, Martin
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supporting information; experimental part
p. 174 - 182
(2010/04/02)
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- 5-ANILINOIMIDAZOPYRIDINES AND METHODS OF USE
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The invention relates to imidazopyridines of formula I with anti-cancer and/or anti-inflammatory activity and more specifically to imidazopyridines which inhibit MEK kinase activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth or treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
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Page/Page column 65
(2009/08/14)
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- CONJUGATES OF ARTEMISININ-RELATED ENDOPEROXIDES AND HYDRAZONE DERIVATIVES FOR THE TREATMENT OF CANCER
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Compounds having an artemisinin-related endoperoxide moiety covalently coupled to a hydrazone moiety through a linker. Compositions and methods for treating cancer using the compounds.
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Page/Page column 14
(2008/06/13)
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- COVALENT CONJUGATES BETWEEN ENDOPEROXIDES AND TRANSFERRIN AND LACTOFERRIN RECEPTOR-BINDING AGENTS
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The invention relates to covalent conjugates between endoperoxides and small peptides and organic compounds that bind to molecular cavities on the transferrin or lactoferrin receptor, and the use of compositions comprising these conjugates to treat cancer, hyperproliferative disorders, inflammatory diseases, and infections.
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Page/Page column 13-14
(2008/06/13)
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- Synthesis of a novel carboxy functionalized PyOX-ligand
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A short and convenient synthesis of a carboxy functionalized PyOX-core is presented. The carboxy functionality offers a wide variety of possibilities for further modification. In this paper, the core is functionalized with a mercapto tail.
- Oila, Markku J.,Tois, Jan E.,Koskinen, Ari M.P.
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p. 967 - 969
(2007/10/03)
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- Ligand creation via linking - A rapid and convenient method for construction of novel supported PyOX-ligands
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A novel supported amino alcohol linker was synthesized and utilized for attachment of picolinic acid derivatives onto different supports. When the resin bound molecule was further activated, the PyOX-moiety could be constructed reliably in enantiopure form. Furthermore, an efficient Pd-catalyzed modification of a picolinic acid derivative is presented.
- Oila, Markku J.,Tois, Jan E.,Koskinen, Ari M.P.
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p. 10748 - 10756
(2007/10/03)
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- Characterizing the "shell phase" formed from amphiphilic picolinates
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The shell phase forms when certain picolinates are subjected to energy input (via sonication or vortexing) while exposed to a water/toluene mixture. A shell, about 600 A thick and containing the picolinate and (very likely) toluene, surround the water droplets that are always produced during the mixing process. Solubility in either phase appears to be deleterious to shell formation. The shells, stable for months, are not easily distorted but can be punctured, even skewered, with a syringe needle without destroying the sphere, yet there is enough mobility among the molecules to repair the physical damage after the needle is removed. This, plus the absence of evidence for crystallinity, suggests a solid or semisolid film forms when picolinates, with the aid of an aromatic solvent, are provided the energy to rearrange themselves on water droplet surfaces. Structure-activity comparisons among the 10 compounds studied indicate that chain-chain association and intermolecular hydrogen bonding are dominant forces in a side-by-side self-assembly of the molecules within the shells. Copyright
- Menger, Fredric M.,Galloway, Ashley L.,Lundberg, Dan
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p. 11914 - 11915
(2007/10/03)
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- Improved carbonylation of heterocyclic chlorides and electronically challenging aryl bromides
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Optimized conditions are described that effect the carbonylation of diverse heterocyclic chlorides to yield the desired alkyl esters. In addition, bromoanilines and bromoanisoles, which normally are poor substrates under standard carbonylation protocols, were efficiently converted to the desired products under these new conditions. The nature of the metal bidentate ligand complex was found to be critical. Specifically, a correlation between ligand bite angle and catalytic efficiency is documented.
- Albaneze-Walker, Jennifer,Bazaral, Charles,Leavey, Tanya,Dormer, Peter G.,Murry, Jerry A.
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p. 2097 - 2100
(2007/10/03)
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- Photodetachment of zwitterions: Probing intramolecular coulomb repulsion and attraction in the gas phase using pyridinium dicarboxylate anions
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Zwitterions are critically important in many biological transformations and are used in numerous chemical processes. The consequences of electrostatic effects on reactivity and physical properties, however, are largely unknown. In this work, we report the results of negative ion photoelectron spectra of nine isomeric pyridinium dicarboxylate zwitterions and three nonzwitterionic methoxycarbonylpyridine carboxylate isomers (-O2CPyrCO2CH3). Information about the intramolecular electrostatic interactions was directly obtained from the photoelectron spectra. The adiabatic and vertical detachment energies were measured and understood in terms of intramolecular Coulombic forces. Calculations at the B3LYP and CCSD(T) level were performed and compared to the experimental electron binding energies. Structures, relative stabilities, and the electron detachment sites also were obtained from the calculations.
- Wang, Xue-Bin,Dacres, Jelena E.,Yang, Xin,Broadus, Katherine M.,Lis, Lev,Wang, Lai-Sheng,Kass, Steven R.
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p. 296 - 304
(2007/10/03)
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- A new soluble polymer-supported sulfonyl linker - Application to the synthesis of cyclic α-amino acids
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A new soluble poly(ethylene glycol)-supported protecting group of the SES (silylethylsulfonyl) type has been prepared and utilized in the synthesis of cyclic amino esters by ring-closing metathesis (RCM). Acidic cleavage from the support was performed to recover the fully deprotected amino acids. More conventional deprotection conditions with fluoride anions resulted in aromatization of the heterocycles in the case of the 6-membered ring and provided a new route to the synthesis of substituted pyridines. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.
- Varray, Stephane,Lazaro, Rene,Martinez, Jean,Lamaty, Frederic
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p. 2308 - 2316
(2007/10/03)
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- Selective palladium-catalysed carbonylations of dichloroquinoline and simple dichloropyridines
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Dichloroquinoline and some dichloropyridines undergo selective alkoxycarbonylation in the presence of carbon monoxide, an alcohol and PdCl2(PPh3)2 as a catalyst, affording chloro-monoester and/or diesters in good yields under selected reaction conditions.
- Najiba, Douja,Carpentier, Jean-Francois,Castanet, Yves,Biot, Christophe,Brocard, Jacques,Mortreux, Andre
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p. 3719 - 3722
(2007/10/03)
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- Pyridopyrazine derivatives for treating alcohol and nicotine abuse and addiction
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Racemic or optically active pyrido[1,2-a]pyrazine derivatives of the formula STR1 wherein X is N or CH and Y represents one of certain pyrazolo, triazolo, tetrazolo or cyclic imido radicals are useful in the treatment of abuse of and/or addiction to such substances as narcotics, alcohol and nicotine.
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- Electrochemical Reduction of Pyridine- and Benzene-Substituted n-Alkyl Esters and Thioic S-Esters in Acetomtrile
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Bulk controlled potential electrolysis experiments have been performed on a wide range of n-alkyl- substituted esters and thioic S-esters of pyridine and benzene in dry acetonitrile with tetraalkylammonium salts as the supporting electrolyte. In most cases, the bulk one-electron reduction of oxygen esters results in unstable or semistable radicals being formed that decompose via loss of the alkyl radical to leave the carboxylate anion in high yield (ca. 70-100%). Benzoate and dinicotinate esters are the exception to this where the final decomposition products are numerous and complicated. For the thioic S-esters, two types of decomposition mechanism have been identified as operating depending on the stability of their anion radicals. Thioic S-ester radical anions that are very unstable (lifetimes in the order of several milliseconds) decompose with loss of the thiolate ion to leave a neutral acyl radical that undergoes aromatic substitution reactions with other acyl radicals to form, among other products, γ-lactones. Thioic S-esters radical anions that are stable for many minutes to hours ultimately decompose via reaction with molecular oxygen to form carboxylate anions.
- Webster, Richard D.,Bond, Alan M.
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p. 1779 - 1787
(2007/10/03)
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- Bis-aza-bicyclic anxiolytic agents
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Anxiolytic agents which are racemic or optically active pyrido[1,2-a]pyrazine derivatives of the formula STR1 wherein x is N or CH and Y represents one of certain pyrazolo, triazolo, tetrazolo or cyclic imido radicals; and intermediates therefor.
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- INDUCTION OF CELL ARREST IN G2: STRUCTURAL SPECIFICITY OF TRIGONELLINE
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Synthetic analogues of N-methyl nicotinic acid, trigonelline, were prepared to test the structural features necessary for the induction of cellular arrest in G2 in Pisum sativum.Analogues that (1) were regioisomers of trigonelline, (2) possessed different 1,3-substituents, ad (3) contained additional substituents on the pyridine ring were tested for their ability to induce cell arrest in G2 and to anatogize trigonelline induced arrest in G2.Only N-methyl-3-quinoline-carboxic acid and 1-methyl nicotinamide induced cell arrest in G2, and 1-methyl-4-pyridine carboxylic acid and 1-methyl-2-pyridine carboxylic acid were effective trigonelline antagonists.These data further support a specific role for trigonelline in the induction of cell arrest in G2.Key words: Pisum sativum; Leguminosae; pea; trigonelline; structural specificity; structural analogues; cell arrest; G2.
- Lynn, David G.,Lewis, David H.,Tramontano, William A.,Evans, Lance S.
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p. 1225 - 1228
(2007/10/02)
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