Assessment of DNA Topoisomerase I Unwinding Activity, Radical Scavenging Capacity, and Inhibition of Breast Cancer Cell Viability of N-alkyl-acridones and N,N-dialkyl-9,9-biacridylidenes
Artikel i vetenskaplig tidskrift, 2019

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,N-dialkyl-9,9-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,N-dialkyl-9,9-biacridylidenes 7-12, revealing that conjugation of the heteroaromatic system plays a significant role on the effective distribution of the compound in the intracellular environment. Cellular investigation of long alkyl derivatives against cell migration exhibited 40-50% wound healing effects and cytoplasm diffusion, while compounds with shorter alkyl chains were accumulated both in the nucleus and cytoplasm. All N,N-dialkyl-9,9-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.

N,N '-dialkyl-9 ' 9-biacridylidenes

radical scavenging capacity

DNA intercalation

cytotoxic activity

DNA binding

topoisomerase I


Marios G. Krokidis

National Centre of Scientific Research Demokritos

Zara Molphy

Dublin City University

Eleni K. Efthimiadou

University of Athens

National Centre of Scientific Research Demokritos

Marianna Kokoli

National Centre of Scientific Research Demokritos

University of Athens

Smaragda Maria Argyri

National Center for Scientific Research “Demokritos”

Irini Dousi

National Centre of Scientific Research Demokritos

Annalisa Masi

Consiglio Nazionale delle Ricerche (CNR)

Kyriakos Papadopoulos

National Centre of Scientific Research Demokritos

Andrew Kellett

Dublin City University

Chryssostomos Chatgilialoglu

Consiglio Nazionale delle Ricerche (CNR)

National Centre of Scientific Research Demokritos


2218-273X (eISSN)

Vol. 9 5 177


Annan medicinsk grundvetenskap


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