In this work, synthesis of alkylamino and aralkylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone was described. For all obtained derivatives biological activity was studied. Cytotoxic activity of the synthesized derivatives towards multidrug resistant MDR human non small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) as well as detection of cell death superoxide anion generation were investigated. Antimicrobial activity towards Gram positive and Gram negative bacteria and fungal cultures was determined. The results showed that strong cytotoxic activity toward cancer cells was improved with simple avarone mimetics. Some derivatives were selective towards MDR cancer cells. The most active derivatives induced apoptosis in both cancer cell lines, but not in normal cells. Superoxide production was induced by 2,6-disubstituted compounds in MDR cancer cells and not by less active 2,5...-disubstituted compounds and was accompanied by the collapse of the mitochondrial transmembrane potential. Two tert-butylquinone derivatives were particularly selective towards MDR cancer cells. Some tert-butylquinone derivatives exhibited a strong antimicrobial activity. (C) 2016 Elsevier Masson SAS. All rights reserved.
TY - JOUR
AU - Jeremić, Marko
AU - Pešić, Milica
AU - Dinić, Jelena
AU - Banković, Jasna
AU - Novaković, Irena T.
AU - Šegan, Dejan M.
AU - Sladić, Dušan
PY - 2016
UR - https://cherry.chem.bg.ac.rs/handle/123456789/2256
AB - In this work, synthesis of alkylamino and aralkylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone was described. For all obtained derivatives biological activity was studied. Cytotoxic activity of the synthesized derivatives towards multidrug resistant MDR human non small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) as well as detection of cell death superoxide anion generation were investigated. Antimicrobial activity towards Gram positive and Gram negative bacteria and fungal cultures was determined. The results showed that strong cytotoxic activity toward cancer cells was improved with simple avarone mimetics. Some derivatives were selective towards MDR cancer cells. The most active derivatives induced apoptosis in both cancer cell lines, but not in normal cells. Superoxide production was induced by 2,6-disubstituted compounds in MDR cancer cells and not by less active 2,5-disubstituted compounds and was accompanied by the collapse of the mitochondrial transmembrane potential. Two tert-butylquinone derivatives were particularly selective towards MDR cancer cells. Some tert-butylquinone derivatives exhibited a strong antimicrobial activity. (C) 2016 Elsevier Masson SAS. All rights reserved.
PB - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
T2 - European Journal of Medicinal Chemistry
T1 - Simple avarone mimetics as selective agents against multidrug resistant cancer cells
VL - 118
SP - 107
EP - 120
DO - 10.1016/j.ejmech.2016.04.011
ER -
@article{
author = "Jeremić, Marko and Pešić, Milica and Dinić, Jelena and Banković, Jasna and Novaković, Irena T. and Šegan, Dejan M. and Sladić, Dušan",
year = "2016",
abstract = "In this work, synthesis of alkylamino and aralkylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone was described. For all obtained derivatives biological activity was studied. Cytotoxic activity of the synthesized derivatives towards multidrug resistant MDR human non small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) as well as detection of cell death superoxide anion generation were investigated. Antimicrobial activity towards Gram positive and Gram negative bacteria and fungal cultures was determined. The results showed that strong cytotoxic activity toward cancer cells was improved with simple avarone mimetics. Some derivatives were selective towards MDR cancer cells. The most active derivatives induced apoptosis in both cancer cell lines, but not in normal cells. Superoxide production was induced by 2,6-disubstituted compounds in MDR cancer cells and not by less active 2,5-disubstituted compounds and was accompanied by the collapse of the mitochondrial transmembrane potential. Two tert-butylquinone derivatives were particularly selective towards MDR cancer cells. Some tert-butylquinone derivatives exhibited a strong antimicrobial activity. (C) 2016 Elsevier Masson SAS. All rights reserved.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris",
journal = "European Journal of Medicinal Chemistry",
title = "Simple avarone mimetics as selective agents against multidrug resistant cancer cells",
volume = "118",
pages = "107-120",
doi = "10.1016/j.ejmech.2016.04.011"
}
Jeremić, M., Pešić, M., Dinić, J., Banković, J., Novaković, I. T., Šegan, D. M.,& Sladić, D.. (2016). Simple avarone mimetics as selective agents against multidrug resistant cancer cells. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris., 118, 107-120.
https://doi.org/10.1016/j.ejmech.2016.04.011
Jeremić M, Pešić M, Dinić J, Banković J, Novaković IT, Šegan DM, Sladić D. Simple avarone mimetics as selective agents against multidrug resistant cancer cells. in European Journal of Medicinal Chemistry. 2016;118:107-120.
doi:10.1016/j.ejmech.2016.04.011 .
Jeremić, Marko, Pešić, Milica, Dinić, Jelena, Banković, Jasna, Novaković, Irena T., Šegan, Dejan M., Sladić, Dušan, "Simple avarone mimetics as selective agents against multidrug resistant cancer cells" in European Journal of Medicinal Chemistry, 118 (2016):107-120,
https://doi.org/10.1016/j.ejmech.2016.04.011 . .
