151562-82-2Relevant academic research and scientific papers
Synthesis, antiprolife ativeactivity and inhibition of tubulinpolymerization by 1,5-and 1,8-disubstituted 10H-anthracen-9-onesbearinga 10-benzylidene or 10-(2-oxo-2-phenylethylidene) moiety
Nickel, Holger C.,Schmidt, Peter,B?hm, Konrad J.,Baasner, Silke,Müller, Klaus,Gerlach, Matthias,Unger, Eberhard,Günther, Eckhard G.,Prinz, Helge
experimental part, p. 3420 - 3438 (2010/08/20)
A novel series of 1,5-and 1,8-disubstituted 10-benzylidene-10H-anthracen-9- ones and 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-ones was synthesized to assess the substituent effects on biological activity. The 3-hydroxy-2,4- dimethoxy-benzylidene analogue 16h displayed strong antiproliferative activity against several tumor cell lines,including multi-drug resistant phenotypes. Flow cytometric studies showed that KB/HeLa cells treated by elected compounds were arrested in the G2/M phases of the cell cycle. Among the compounds tested for inhibition of tubulin polymerization,14 compounds proved to be exceptionally active with IC50 values 1 mM. In the 1,5-dichloro-derived series of benzy-lideneanthracenones,E/Z isomers were separated and biological effects were monitored. We found that the olefinic geometry had no significant effect on biological activity. Furthermore,the E isomeric 1,5-dichloro-substituted phenacylidenes entirely proved to be more potent inhibitors of tubulin polymerization than the recently described 10-(2-oxo-2-phenylethylidene)-10H- anthracen-9-ones. In conclusion,the present study improves understanding of the action of anthracenone-based tubulin polymerization inhibitors and contributes to the design of further potent anti-tubulin drugs.
Antipsoriatic Anthrones with Modulated Redox Properties. 1. Novel 10-Substituted 1,8-Dihydroxy-9(10H)-anthracenones as Inhibitors of 5-Lipoxygenase
Mueller, Klaus,Guerster, Dieter,Piwek, Susanne,Wiegrebe, Wolfgang
, p. 4099 - 4107 (2007/10/02)
The syntheses, the biological evaluation, and the structure-activity relationships of a novel series of 1,8-dihydroxy-9(10H)-anthracenones bearing acyl-, alkyl-, or alkylidene-linked aromatic substituents in the 10-position are described.The phenylacyl and phenylalkylidene analogs were far more potent inhibitors of 5-lipoxygenase (5-LO) from bovine polymorphonuclear leukocytes (IC50 values in the 10-7 M range) than the antipsoriatic drug anthralin, whereas phenylalkyl analogs were only weak inhibitors.Among the active compounds were both potent generators of hydroxyl radicals, as determined by deoxyribose degradation, and strong reducers of the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH).However, several derivatives of this series maintained 5-LO inhibitory activity but did not generate hydroxyl radicals and were not reactive with DPPH.In particular, phenylacyl analogs were also 6 times more efficient in inhibition of lipid peroxidation in model membranes than anthralin.Structure-activity relationships have shown that the presence of free phenolic groups in the attached aromatic ring is beneficial but not required for 5-LO inhibitory potency.The inhibitory potency in the 10-phenylacyl series increased with the length of the acyl chain with three methylene units being the optimum, suggesting a specific enzyme interaction which would not be expected for nonspecific redox inhibitors.
