10-(2-oxo-2-Phenylethylidene)-10H-anthracen-9-ones as Highly Active Antimicrotubule Agents: Synthesis, Antiproliferative Activity, and Inhibition of Tubulin Polymerization

Prinz H, Schmidt P, Böhm KJ, Baasner S, Müller K, Unger E, Gerlach M, Günther EG

Zusammenfassung

A series of 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-ones were synthesized and evaluated for interactions with tubulin and for antiproliferative activity against a panel of human and rodent tumor cell lines. The 4-methoxy analogue 17b was most potent, displaying IC50 values ranging from 40 to 80 nM, including multidrug resistant phenotypes, and had excellent activity as an inhibitor of tubulin polymerization (IC50 = 0.52 mu M). Concentration-dependent flow cytometric studies showed that KB/HeLa cells treated with 17b were arrested in the G2/M phases of the cell cycle (EC50 = 90 nM). In competition experiments, 17b strongly displaced [H-3]-colchicine from its binding site in the tubulin. The results obtained demonstrate that the anti proliferative activity is related to the inhibition of tubulin polymerization.

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