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

Dinic, Jelena

Bankovic, Jasna
Novaković, Irena

Šegan, Dejan

Sladić, Dušan

Article (Published version)

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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
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)
DOI: 10.1016/j.ejmech.2016.04.011
ISSN: 0223-5234
PubMed: 27128177