158264-59-6Relevant academic research and scientific papers
5-Hydroxy-2-(phenyl or styryl)chromones: One-pot synthesis and C-6, C-8 13C NMR assignments
Silva,Pinto,Cavaleiro
, p. 5899 - 5902 (1994)
A new procedure to synthesise 5-hydroxy derivatives of 2-phenyl- and 2- styrylchromones is reported. The assignments of their C-6 and C-8 atoms, made by proton-coupled 13C and selective INEPT NMR spectroscopy, show that the literature data for such carbon centres must be interchanged.
Structural basis for the activity of the RSK-specific inhibitor, SL0101
Smith, Jeffrey A.,Maloney, David J.,Hecht, Sidney M.,Lannigan, Deborah A.
, p. 5018 - 5034 (2008/03/12)
Inappropriate activity of p90 ribosomal S6 kinase (RSK) has been implicated in various human cancers as well as other pathologies. We previously reported the isolation, characterization, and synthesis of the natural product kaempferol 3-O-(3″,4″-di-O-acetyl-α-l-rhamnopyranoside), termed SL0101 [Smith, J. A.; Poteet-Smith, C. E.; Xu, Y.; Errington, T. M.; Hecht, S. M.; Lannigan, D. A. Cancer Res., 2005, 65, 1027-1034: Xu, Y.-M; Smith, J. A.; Lannigan, D. A.; Hecht, S. M. Bioorg. Med. Chem., 2006, 14, 3974-3977: Maloney, D. J.; Hecht, S. M. Org. Lett., 2005, 7, 1097-1099]. SL0101 is a potent and specific inhibitor of RSK; therefore, we performed an analysis of the structural basis for the inhibitory activity of this lead compound. In in vitro kinase assays we found that acylation of the rhamnose moiety and the 4′, 5, and 7-hydroxyl groups are responsible for maintaining a high affinity interaction of RSK with SL0101. It is likely that the hydroxyl groups facilitate RSK binding through their ability to form hydrogen bonds. To determine whether the SL0101 derivatives were specific for inhibition of RSK we analyzed their ability to preferentially inhibit the growth of the human breast cancer line, MCF-7, compared to the normal human breast line, MCF-10A. We have previously validated this differential growth assay as a convenient readout for analyzing the specificity of RSK inhibitors [Smith, J. A.; Maloney, D. J.; Clark, D. E.; Xu, Y.-M.; Hecht, S. M.; Lannigan, D. A. Bioorg. Med. Chem., 2006, 14, 6034-6042]. We found that acylation of the rhamnose moiety was essential for maintaining the selectivity for RSK inhibition in intact cells. Further, the efficacy of SL0101 in intact cells is limited by cellular uptake as well as possible hydrolysis of the acetyl groups on the rhamnose moiety by ubiquitous intracellular esterases. These studies should facilitate the development of a RSK inhibitor, based on the SL0101 pharmacophore, as an anti-cancer chemotherapeutic agent.
Synthesis of 3-(2-benzyloxy-6-hydroxyphenyl)-1-methylpyrazoles by the reaction of chromones with methylhydrazine
Pinto,Silva,Cavaleiro
, p. 1629 - 1634 (2007/10/03)
The 3-(2-benzyloxy-6-hydroxyphenyl)-5-(methyl, phenyl or styryl)pyrazoles were prepared from the reaction of 2-(methyl, phenyl or styryl)chromones with methylhydrazine. The structure of these compounds has been determined by several nmr techniques, and the reaction mechanism is discussed.
Syntheses of 5-Hydroxy-2-(phenyl or styryl)chromones and of Some Halo Derivatives
Pinto, Diana C. G. A.,Silva, Artur M. S.,Cavaleiro, Jose A. S.
, p. 1887 - 1893 (2007/10/03)
One-pot syntheses of 5-hydroxy-2-(phenyl or styryl)chromones and the corresponding 6- and 8-monoiodo- and 6,8-diiodochromones have been developed. The procedures involve oxidative cyclization of 2′-benzyloxy-6′-hydroxychalcones and 2′-benzyloxy-6′-hydroxy-2-cinnamylideneacetophenones and electrophilic substitution processes on the chromone moieties; such procedures were also applied to the syntheses of 6,8-dibromochromone derivatives.
