Design, Synthesis, and Cytotoxic Activity Evaluation of New Linear Pyranoxanthone Aminoderivatives

With the aim of enlightening some structure-activity correlation within the pyranoxanthenone series, we have designed and synthesized a number of new 5-aminosubstituted pyrano[3,2-b] xanthen-6-ones bearing various 12-substituents. In vitro cytotoxic potencies of the new derivatives toward the murine leukemia L1210 cell line, human colorectal adenocarcinoma (HT-29), and human uterine sarcoma (MES-SA and its 100-fold resistant to doxorubicin variant MES-SA/Dx5) cell lines, are described and compared with that of reference drugs. Among the studied compounds, those possessing a second aminosubstituted side-chain exhibit interesting cytotoxic activity against the solid tumor cell lines, and they retain activity against the multidrug resistant MES-SA/Dx5 subline. Their selective effect on a phase of the cell cycle was evaluated using HT-29 cells providing evidence that the compounds induce a G0/G1 arrest.