Indenoisoquinoline derivatives as topoisomerase I inhibitors that suppress angiogenesis by affecting the HIF signaling pathway

Both Topoisomerase I and angiogenesis factors have caught pharmaceutical chemists' attention in antitumor chemotherapy field. A series of indenoisoquinoline derivatives with high Top I inhibitory from our previous work were evaluated for their anti-angiogenesis property using classic in vitro and vivo models. The results demonstrated that all the compounds could significantly decrease the proliferation of endothelial cells in a concentration-dependent manner. Besides, compound 1 exerted marked inhibition of angiogenesis in vivo and in vitro models. The HIF signaling pathway in HUVECs was affected by compound 1 in a time-dependent manner. These data suggest that the tested compound 1 could serve as promising lead compound for further development and optimization. (C) 2013 Elsevier Masson SAS. All rights reserved.