Simple avarone mimetics as selective agents against multidrug resistant cancer cells
Authorized Users Only
2016
Authors
Jeremić, Marko
Pešić, Milica

Dinić, Jelena

Bankovic, Jasna
Novaković, Irena

Šegan, Dejan

Sladić, Dušan

Article (Published version)

Metadata
Show full item recordAbstract
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.
Keywords:
Quinones / Anticancer activity / Multidrug resistant / Apoptosis / ROS generation / Mitochondrial potentialSource:
European Journal of Medicinal Chemistry, 2016, 118, 107-120Publisher:
- Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
Funding / projects:
- Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-172055)
- Identification of predictive molecular markers for cancer progression, response to therapy and disease outcome (RS-41031)
Note:
- The peer-reviewed version: https://cer.ihtm.bg.ac.rs/handle/123456789/4579
- Supplementary material: https://cer.ihtm.bg.ac.rs/handle/123456789/4580
Related info:
- Version of
https://cer.ihtm.bg.ac.rs/handle/123456789/4579 - Referenced by
https://cer.ihtm.bg.ac.rs/handle/123456789/4580
DOI: 10.1016/j.ejmech.2016.04.011
ISSN: 0223-5234
PubMed: 27128177
WoS: 000377312400011
Scopus: 2-s2.0-84964477857
Collections
Institution/Community
IHTMTY - JOUR AU - Jeremić, Marko AU - Pešić, Milica AU - Dinić, Jelena AU - Bankovic, Jasna AU - Novaković, Irena AU - Šegan, Dejan AU - Sladić, Dušan PY - 2016 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1862 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. 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 Bankovic, Jasna and Novaković, Irena and Šegan, Dejan 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.", 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., Bankovic, J., Novaković, I., Šegan, D.,& 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, Bankovic J, Novaković I, Šegan D, 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, Bankovic, Jasna, Novaković, Irena, Šegan, Dejan, 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 . .