Synthesis, cytotoxic activities and structure–activity relationships of topoisomerase I inhibitors: Indolizinoquinoline-5,12-dione derivatives

A series of indolizinoquinoline-5,12-dione derivatives (IQDs) are synthesized and evaluated for their cytotoxic activities toward human lung adenocarcinoma (GLC-82), large-cell lung carcinoma (NCI-H460), promyelocytic leukemia (HL-60) and breast carcinoma (MCF-7) cells by MTT method. Most of the IQDs show significant cytotoxic potency. In addition, the evaluation of structure–activity relationships indicated that the incorporation of electron-withdrawing substituents at the C or D ring will enhance the activities of the target compounds distinctly. The topoisomerase I inhibitory activity is also measured.

A series of indolizinoquinoline-5,12-dione derivatives are synthesized and evaluated for cytotoxic activities. The synthetic compounds show significant cytotoxic activities against tumor cells. The structure-activity relationships and topoisomerase I inhibitory activity of target compounds are discussed.Figure optionsDownload as PowerPoint slide