Abstract
Several new amino-substituted acridone and xanthone derivatives have been designed and synthesized, using an efficient methodology from suitable acridone- or xanthone-carboxylic acid intermediates. The antiproliferative activity of the target compounds has been evaluated against four cancer cell lines, namely breast adenocarcinoma MCF-7, acute lymphocytic leukemia CCRF-CEM, and its doxorubicin-resistant variant CEM/ADR5000 and prostate cancer PC-3 cell lines. Selected derivatives have also been tested against the urinary bladder T24 and metastatic melanoma WM266-4 cancer cell lines. Two nitro substituted acridones, bearing a basic side chain as well, were endowed with a remarkable profile against the majority of the cell lines tested, with IC50 values in the low micromolar range. Both compounds cause accumulation at G0/G1 phase, induce apoptosis, and act as potent autophagy inhibitors in PC-3 cells, suggesting their further evaluation in various pathophysiological environments, conditions, and regimens.
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