Mannich Reaction between 1,3-Dihydroxyacridones and Their 5-Aza Derivatives and Cyclic Amines: A Simple Pathway to New Anticancer Scaffold

In this study, we proposed for the first time a synthetic route to 4-aminomethyl 1,3-dihydroxyacridones and their 5-aza derivatives using Mannich reaction between 1,3-dihydroxyacridones and aliphatic amines. This approach offers several advantages, including high product yields, controllable reaction selectivity, and easy handling of reaction. As a result of this study, five acridone Mannich bases were synthesized, and their anticancer evaluation reveals moderate activity against the HCT 116 colorectal cancer (IC50 up to 86 μM, SI > 1.1) and HuTu 80 duodenal adenocarcinoma (IC50 up to 38 μM, SI > 2.7) cell lines.