Assessment of DNA Topoisomerase I Unwinding Activity, Radical Scavenging Capacity, and Inhibition of Breast Cancer Cell Viability of N-alkyl-acridones and N,N0-dialkyl-9,90-biacridylidenes
| Autor: | Marios G. Krokidis 1, Zara Molphy 2, Eleni K. Efthimiadou 1, 3, Marianna Kokoli 1, Smaragda-Maria Argyri 1, y, Irini Dousi 1, Annalisa Masi 4, Kyriakos Papadopoulos 1, Andrew Kellett 2, Chryssostomos Chatgilialoglu 1, 4 |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Biomolecules 9 (2019): 177. doi:10.3390/biom9050177 info:cnr-pdr/source/autori:Marios G. Krokidis 1, Zara Molphy 2, Eleni K. Efthimiadou 1,3, Marianna Kokoli 1,3, Smaragda-Maria Argyri 1,y, Irini Dousi 1, Annalisa Masi 4, Kyriakos Papadopoulos 1,*, Andrew Kellett 2 and Chryssostomos Chatgilialoglu 1,4,*/titolo:Assessment of DNA Topoisomerase I Unwinding Activity, Radical Scavenging Capacity, and Inhibition of Breast Cancer Cell Viability of N-alkyl-acridones and N,N0-dialkyl-9,90-biacridylidenes/doi:10.3390%2Fbiom9050177/rivista:Biomolecules/anno:2019/pagina_da:177/pagina_a:/intervallo_pagine:177/volume:9 |
| DOI: | 10.3390/biom9050177 |
| Popis: | The anticancer activity of acridone derivatives has attracted increasing interest, therefore, a variety of substituted analogs belonging to this family have been developed and evaluated for their anti-cancer properties. A series of N-alkyl-acridones 1-6 and N,N0-dialkyl-9,90-biacridylidenes 7-12 with variable alkyl chains were examined for their topoisomerase I activity at neutral and acidic conditions as well as for their binding capacity to calf thymus and possible radical trapping antioxidant activity. It was found that at a neutral pH, topoisomerase I activity of both classes of compounds was similar, while under acidic conditions, enhanced intercalation was observed. N-alkyl-acridone derivatives 1-6 exhibited stronger, dose-dependent, cytotoxic activity against MCF-7 human breast epithelial cancer cells than N,N0-dialkyl-9,90-biacridylidenes 7-12, revealing that conjugation of the heteroaromatic system plays a significant role on the eective distribution of the compound in the intracellular environment. Cellular investigation of long alkyl derivatives against cell migration exhibited 40-50% wound healing eects and cytoplasm diusion, while compounds with shorter alkyl chains were accumulated both in the nucleus and cytoplasm. All N,N0-dialkyl-9,90-biacridylidenes showed unexpected high scavenging activity towards DPPH or ABTS radicals which may be explained by higher stabilization of radical cations by the extended conjugation of heteroaromatic ring system. |
| Databáze: | OpenAIRE |
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