Novel anthraquinone based chalcone compounds were synthesized starting from 1-acetylanthraquinone in a Claisen-Schmidt reaction and evaluated for their anticancer potential against three human cancer cell lines. Compounds 4a, 4b and 4j showed promising activity in inhibition of HeLa cells with IC50 values ranging from 2.36 to 2.73 mu M and low cytotoxicity against healthy MRC-5 cell lines. The effects that compounds produces on the cell cycle were investigated by flow cytometry. It was found that 4a, 4b and 4j cause the accumulation of cells in the S and G2/M phases in a dose-dependent manner and induce caspase-dependent apoptosis. All of three compounds exhibit calf thymus DNA-binding activity. The determined binding constants by absorption titrations (2.65 x 10(3) M-1, 1.36 x 10(3) M(-1)and 2.51 x 10(3) M-1 of 4a/CT-DNA, 4b/CT-DNA and 4j/CT-DNA, respectively) together with fluorescence displacement analysis designate 4a, 4b and 4j as strong minor groove binders, but no cleavage of pl...asmid DNA was observed.
Keywords:
Chalcone / Anthraquinone / cytotoxicity / Apoptosis / DNA study
Source:
European Journal of Medicinal Chemistry, 2015, 89, 401-410
Publisher:
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
TY - JOUR
AU - Markovic, Violeta
AU - Debeljak, Nevena
AU - Stanojković, Tatjana
AU - Kolundzija, Branka
AU - Sladić, Dušan
AU - Vujčić, Miroslava
AU - Janović, Barbara
AU - Tanic, Nikola
AU - Perovic, Milka
AU - Tesic, Vesna
AU - Antic, Jadranka
AU - Joksovic, Milan D.
PY - 2015
UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1745
AB - Novel anthraquinone based chalcone compounds were synthesized starting from 1-acetylanthraquinone in a Claisen-Schmidt reaction and evaluated for their anticancer potential against three human cancer cell lines. Compounds 4a, 4b and 4j showed promising activity in inhibition of HeLa cells with IC50 values ranging from 2.36 to 2.73 mu M and low cytotoxicity against healthy MRC-5 cell lines. The effects that compounds produces on the cell cycle were investigated by flow cytometry. It was found that 4a, 4b and 4j cause the accumulation of cells in the S and G2/M phases in a dose-dependent manner and induce caspase-dependent apoptosis. All of three compounds exhibit calf thymus DNA-binding activity. The determined binding constants by absorption titrations (2.65 x 10(3) M-1, 1.36 x 10(3) M(-1)and 2.51 x 10(3) M-1 of 4a/CT-DNA, 4b/CT-DNA and 4j/CT-DNA, respectively) together with fluorescence displacement analysis designate 4a, 4b and 4j as strong minor groove binders, but no cleavage of plasmid DNA was observed.
PB - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
T2 - European Journal of Medicinal Chemistry
T1 - Anthraquinone-chalcone hybrids: Synthesis, preliminary antiproliferative evaluation and DNA-interaction studies
VL - 89
SP - 401
EP - 410
DO - 10.1016/j.ejmech.2014.10.055
ER -
@article{
author = "Markovic, Violeta and Debeljak, Nevena and Stanojković, Tatjana and Kolundzija, Branka and Sladić, Dušan and Vujčić, Miroslava and Janović, Barbara and Tanic, Nikola and Perovic, Milka and Tesic, Vesna and Antic, Jadranka and Joksovic, Milan D.",
year = "2015",
abstract = "Novel anthraquinone based chalcone compounds were synthesized starting from 1-acetylanthraquinone in a Claisen-Schmidt reaction and evaluated for their anticancer potential against three human cancer cell lines. Compounds 4a, 4b and 4j showed promising activity in inhibition of HeLa cells with IC50 values ranging from 2.36 to 2.73 mu M and low cytotoxicity against healthy MRC-5 cell lines. The effects that compounds produces on the cell cycle were investigated by flow cytometry. It was found that 4a, 4b and 4j cause the accumulation of cells in the S and G2/M phases in a dose-dependent manner and induce caspase-dependent apoptosis. All of three compounds exhibit calf thymus DNA-binding activity. The determined binding constants by absorption titrations (2.65 x 10(3) M-1, 1.36 x 10(3) M(-1)and 2.51 x 10(3) M-1 of 4a/CT-DNA, 4b/CT-DNA and 4j/CT-DNA, respectively) together with fluorescence displacement analysis designate 4a, 4b and 4j as strong minor groove binders, but no cleavage of plasmid DNA was observed.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris",
journal = "European Journal of Medicinal Chemistry",
title = "Anthraquinone-chalcone hybrids: Synthesis, preliminary antiproliferative evaluation and DNA-interaction studies",
volume = "89",
pages = "401-410",
doi = "10.1016/j.ejmech.2014.10.055"
}
Markovic, V., Debeljak, N., Stanojković, T., Kolundzija, B., Sladić, D., Vujčić, M., Janović, B., Tanic, N., Perovic, M., Tesic, V., Antic, J.,& Joksovic, M. D.. (2015). Anthraquinone-chalcone hybrids: Synthesis, preliminary antiproliferative evaluation and DNA-interaction studies. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris., 89, 401-410.
https://doi.org/10.1016/j.ejmech.2014.10.055
Markovic V, Debeljak N, Stanojković T, Kolundzija B, Sladić D, Vujčić M, Janović B, Tanic N, Perovic M, Tesic V, Antic J, Joksovic MD. Anthraquinone-chalcone hybrids: Synthesis, preliminary antiproliferative evaluation and DNA-interaction studies. in European Journal of Medicinal Chemistry. 2015;89:401-410.
doi:10.1016/j.ejmech.2014.10.055 .
Markovic, Violeta, Debeljak, Nevena, Stanojković, Tatjana, Kolundzija, Branka, Sladić, Dušan, Vujčić, Miroslava, Janović, Barbara, Tanic, Nikola, Perovic, Milka, Tesic, Vesna, Antic, Jadranka, Joksovic, Milan D., "Anthraquinone-chalcone hybrids: Synthesis, preliminary antiproliferative evaluation and DNA-interaction studies" in European Journal of Medicinal Chemistry, 89 (2015):401-410,
https://doi.org/10.1016/j.ejmech.2014.10.055 . .
