Skip to Content
MilliporeSigma
  • 9-Benzylidene-naphtho[2,3-b]thiophen-4-ones as novel antimicrotubule agents-synthesis, antiproliferative activity, and inhibition of tubulin polymerization.

9-Benzylidene-naphtho[2,3-b]thiophen-4-ones as novel antimicrotubule agents-synthesis, antiproliferative activity, and inhibition of tubulin polymerization.

Journal of medicinal chemistry (2006-12-22)
Anne Zuse, Peter Schmidt, Silke Baasner, Konrad J Böhm, Klaus Müller, Matthias Gerlach, Eckhard G Günther, Eberhard Unger, Helge Prinz
ABSTRACT

A novel series of 9-benzylidene-naphtho[2,3-b]thiophen-4-ones and structurally related compounds were synthesized and evaluated for their ability to inhibit tubulin polymerization. The 4-hydroxy-3,5-dimethoxy-benzylidene analogue 15d was identified as a potent cytotoxic agent in an assay based on K562 leukemia cells. Antiproliferative activity of 15d and the 2,4-dimethoxy-3-hydroxy-benzylidene analogue 15e was additionally evaluated against a panel of 12 tumor cell lines, including multidrug resistant phenotypes. All resistant cell lines were sensitive to these compounds. Concentration-dependent flow cytometric studies showed that K562 cells as well as KB/HeLa cells treated by 15d were arrested in the G2/M phases of the cell cycle. Moreover, four compounds strongly inhibited tubulin polymerization with activities higher or comparable to those of the reference compounds. In competition experiments, the most active compounds strongly displaced radiolabeled colchicine from its binding site in the tubulin, showing IC50 values virtually 3- to 4-fold lower than that of colchicine.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Vinblastine sulfate salt, ≥97% (HPLC)
Sigma-Aldrich
Nocodazole, ≥99% (TLC), powder
Sigma-Aldrich
Colchicine, ≥95% (HPLC), powder
Sigma-Aldrich
Colchicine, BioReagent, suitable for plant cell culture, ≥95% (HPLC)
Sigma-Aldrich
Podophyllotoxin