| Summary: | 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 <i>N</i>-alkyl-acridones <b>1</b>−<b>6</b> and <i>N</i>,<i>N</i>′-dialkyl-9,9′-biacridylidenes <b>7</b>−<b>12</b> 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. <i>N</i>-alkyl-acridone derivatives <b>1</b>−<b>6</b> exhibited stronger, dose-dependent, cytotoxic activity against MCF-7 human breast epithelial cancer cells than <i>N</i>,<i>N′</i>-dialkyl-9,9′-biacridylidenes <b>7</b>−<b>12</b>, 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 <i>N</i>,<i>N′</i>-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.
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