(E)-4-Aryl-4-oxo-2-butenoic acid amides, chalconeearoylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization
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2013
Authors
Vitorović-Todorović, Maja D.
Erić-Nikolić, Aleksandra
Kolundžija, Branka
Hamel, Ernest

Ristić, Slavica S.
Juranić, Ivan

Drakulić, Branko

Article (Published version)

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Show full item recordAbstract
Antiproliferative activity of twenty-nine (E)-4-aryl-4-oxo-2-butenoic acid amides against three human
tumor cell lines (HeLa, FemX, and K562) is reported. Compounds showed antiproliferative activity in
one-digit micromolar to submicromolar concentrations. The most active derivatives toward all the cell
lines tested bear alkyl substituents on the aroyl moiety of the molecules. Fourteen compounds showed
tubulin assembly inhibition at concentrations <20 mM. The most potent inhibitor of tubulin assembly
was unsubstituted compound 1, with IC50 ¼ 2.9 mM. Compound 23 had an oral LD50 in vivo of 45 mg/kg in
mice. Cell cycle analysis on K562 cells showed that compounds 1, 2 and 23 caused accumulation of cells
in the G2/M phase, but inhibition of microtubule polymerization is not the principal mode of action of
the compounds. Nevertheless, they may be useful leads for the design of a new class of antitubulin
agents.
Keywords:
(E)-4-Aryl-4-oxo-2-butenoic acid amides / chalconeearoylacrylic acid chimeras / antiproliferative activity / inhibition of tubulin polymerizationSource:
European Journal of Medicinal Chemistry, 2013, 62, 40-50Publisher:
- Elsevier Masson SAS.
Projects:
DOI: 10.1016/j.ejmech.2013.01.006
ISSN: 0223-5234