- Oxidation of putrescine and cadaverine derivatives by diamine oxidases
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A range of putrescine and cadaverine derivatives has been synthesized and assayed as substrates for the diamine oxidases from pea seedlings and pig kidney. KM and Vmax data are reported, mainly for the pea enzyme. N-Alkylputrescines and C-alkylcadaverines are generally poorer substrates than the parent compounds with up to 4500-fold reduction in Vmax. There is significantly less variation in KM values, indicating that the binding site of the pea enzyme is relatively non-specific and that enzymic specificity lies at the catalytic stage. This suggests that poor substrates might act as convenient, short-lived inhibitors of diamine oxidases.
- Equi, Angela M.,Brown, Alison M.,Cooper, Alan,Her, Surjit K.,Watson, Allan B.,Robins, David J.
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- Further studies on bis-charged tetraazacyclophanes as potent inhibitors of small conductance Ca2+-activated K+ channels
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Previously, quinolinium-based tetraazacyclophanes, such as UCL 1684 and UCL 1848, have been shown to be extraordinarily sensitive to changes in chemical structure (especially to the size of the cyclophane system) with respect to activity as potent non-peptidic blockers of the small conductance Ca 2+-activated K+ ion channels (SKCa). The present work has sought to optimize the structure of the linking chains in UCL 1848. We report the synthesis and SKCa channel-blocking activity of 29 analogues of UCL 1848 in which the central CH2 of UCL 1848 is replaced by other groups X or Y = O, S, CF2, CO, CHOH, CC, CHCH, CHMe to explore whether subtle changes in bond length or flexibility can improve potency still further. The possibility of improving potency by introducing ring substituents has also been explored by synthesizing and testing 25 analogues of UCL 1684 and UCL 1848 with substituents (NO2, NH2, CF 3, F, Cl, CH3, OCH3, OCF3, OH) in the 5, 6 or 7 positions of the aminoquinolinium rings. As in our earlier work, each compound was assayed for inhibition of the afterhyperpolarization (AHP) in rat sympathetic neurons, an action mediated by the SK3 subtype of the SK Ca channel. One of the new compounds (39, R7 = Cl, UCL 2053) is twice as potent as UCL 1848 and UCL 1684: seven are comparable in activity.
- Yang, Donglai,Arifhodzic, Lejla,Ganellin, C. Robin,Jenkinson, Donald H.
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supporting information
p. 907 - 923
(2013/07/27)
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- Sequestering agent for uranyl chelation: a new family of CAMS ligands
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The synthesis of new dipodal bis-sulfocatecholamide uranophiles is presented. Their binding abilities for uranyl cation were determined by UV spectrophotometry in aqueous media under various pH conditions and further studied by 1H NMR analysis of the resonance signal of both aromatic protons of the sulfocatecholamide groups. The results showed that the efficiency of these hydrosoluble chelating agents depends on the nature of the spacers. Each ligand shows a more or less pronounced affinity for uranium. The best receptor is the ligand CYCAMS 5d obtained as a mixture of cis/trans isomers, which achieves the best compromise between rigidity and steric hindrance.
- Leydier, Antoine,Lecerclé, Delphine,Pellet-Rostaing, Stéphane,Favre-Reguillon, Alain,Taran, Frédéric,Lemaire, Marc
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p. 6662 - 6669
(2008/12/20)
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- Potent inducers of terminal differentiation and methods of use thereof
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The invention provides compounds, several of which belong to a class having two or more nonpolar components connected by a polar group and having polar groups on the termini of the compound. The invention also concerns a method of selectively inducing termini differentiation of neoplastic cells and thereby inhibiting proliferation of such cells which comprises contacting the cells under suitable condition with an amount of the compound effect to selectively induce terminal differentiation. Moreover, the invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells which comprises administering to the patient an amount of the compound effective to selectively induce terminal differentiation of such neoplastic cells, thereby inhibiting their proliferation and suppressing oncogenicity. Lastly, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound in an amount effective less than an amount which would cause toxicity in the patient.
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