Simple avarone mimetics as selective agents against multidrug resistant cancer cells
2016
Authors:
Jeremić, MarkoPešić, Milica
Dinić, Jelena
Banković, Jasna
Novaković, Irena
Šegan, Dejan
Sladić, Dušan
Document Type:
Article (Accepted 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.
Note:
This is a post-peer-review, pre-copyedit version of article: Jeremić M, Pešić M, Dinić J, Banković J, Novaković I, Šegan D, Sladić D. Simple avarone mimetics as selective agents against multidrug resistant cancer cells. Eur. J. Med. Chem. 2016;118:107-20. The final authenticated version is available online at: https://dx.doi.org/10.1016/j.ejmech.2016.04.011.
Keywords:
Quinones; Anticancer activity; Multidrug resistant; Apoptosis; ROS generation; Mitochondrial potentialSource:
European Journal of Medicinal Chemistry, 2016, 118, 107-120Funding / projects:
- Identification of predictive molecular markers for cancer progression, response to therapy and disease outcome (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41031)
- Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-MESTD-Basic Research (BR or ON)-172055)
DOI: 10.1016/j.ejmech.2016.04.011
ISSN: 0223-5234
PubMed: 27128177
WoS: 000377312400011
Scopus: 2-s2.0-84964477857
URI
https://www.sciencedirect.com/science/article/pii/S0223523416302938?via%3Dihubhttps://radar.ibiss.bg.ac.rs/123456789/3885