(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.
Funding / projects:
- Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-MESTD-Basic Research (BR or ON)-172035)
DOI: 10.1016/j.ejmech.2013.01.006
ISSN: 0223-5234
WoS: 000318577500005
Scopus: 2-s2.0-84872676363
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IHTMTY - JOUR AU - Vitorović-Todorović, Maja D. AU - Erić-Nikolić, Aleksandra AU - Kolundžija, Branka AU - Hamel, Ernest AU - Ristić, Slavica S. AU - Juranić, Ivan AU - Drakulić, Branko PY - 2013 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2873 AB - 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. PB - Elsevier Masson SAS. T2 - European Journal of Medicinal Chemistry T1 - (E)-4-Aryl-4-oxo-2-butenoic acid amides, chalconeearoylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization VL - 62 SP - 40 EP - 50 DO - 10.1016/j.ejmech.2013.01.006 ER -
@article{ author = "Vitorović-Todorović, Maja D. and Erić-Nikolić, Aleksandra and Kolundžija, Branka and Hamel, Ernest and Ristić, Slavica S. and Juranić, Ivan and Drakulić, Branko", year = "2013", abstract = "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.", publisher = "Elsevier Masson SAS.", journal = "European Journal of Medicinal Chemistry", title = "(E)-4-Aryl-4-oxo-2-butenoic acid amides, chalconeearoylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization", volume = "62", pages = "40-50", doi = "10.1016/j.ejmech.2013.01.006" }
Vitorović-Todorović, M. D., Erić-Nikolić, A., Kolundžija, B., Hamel, E., Ristić, S. S., Juranić, I.,& Drakulić, B.. (2013). (E)-4-Aryl-4-oxo-2-butenoic acid amides, chalconeearoylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization. in European Journal of Medicinal Chemistry Elsevier Masson SAS.., 62, 40-50. https://doi.org/10.1016/j.ejmech.2013.01.006
Vitorović-Todorović MD, Erić-Nikolić A, Kolundžija B, Hamel E, Ristić SS, Juranić I, Drakulić B. (E)-4-Aryl-4-oxo-2-butenoic acid amides, chalconeearoylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization. in European Journal of Medicinal Chemistry. 2013;62:40-50. doi:10.1016/j.ejmech.2013.01.006 .
Vitorović-Todorović, Maja D., Erić-Nikolić, Aleksandra, Kolundžija, Branka, Hamel, Ernest, Ristić, Slavica S., Juranić, Ivan, Drakulić, Branko, "(E)-4-Aryl-4-oxo-2-butenoic acid amides, chalconeearoylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization" in European Journal of Medicinal Chemistry, 62 (2013):40-50, https://doi.org/10.1016/j.ejmech.2013.01.006 . .