Synthesis, antiproliferative activity and inhibition of tubulin polymerization by 1,5- and 1,8-disubstituted 10H-anthracen-9-ones bearing a 10-benzylidene or 10-(2-oxo-2-phenylethylidene) moiety
In: European Journal of Medicinal Chemistry, Jg. 45 (2010-08-01), Heft 8, S. 3420-3438
academicJournal
Zugriff:
Abstract: 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 μM. In the 1,5-dichloro-derived series of benzylideneanthracenones, 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. [Copyright &y& Elsevier]
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Synthesis, antiproliferative activity and inhibition of tubulin polymerization by 1,5- and 1,8-disubstituted 10H-anthracen-9-ones bearing a 10-benzylidene or 10-(2-oxo-2-phenylethylidene) moiety
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Autor/in / Beteiligte Person: | Nickel, Holger C. ; Schmidt, Peter ; Böhm, Konrad J. ; Baasner, Silke ; Müller, Klaus ; Gerlach, Matthias ; Unger, Eberhard ; Günther, Eckhard G. ; Prinz, Helge |
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Zeitschrift: | European Journal of Medicinal Chemistry, Jg. 45 (2010-08-01), Heft 8, S. 3420-3438 |
Veröffentlichung: | 2010 |
Medientyp: | academicJournal |
ISSN: | 0223-5234 (print) |
DOI: | 10.1016/j.ejmech.2010.04.032 |
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