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Indenoisoquinoline derivatives as topoisomerase I inhibitors that suppress angiogenesis by affecting the HIF signaling pathway |
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| Authors: | Xiaoli Xu Fang Liu Shengmiao Zhang Jianmin Jia Zhiyu Li Xiaoke Guo Yong Yang Haopeng Sun Qidong You |
| Affiliation: | 1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China;2. Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China;3. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China;4. Department of Physiology, School of Pharmacy, China Pharmaceutical University, Nanjing, China |
| Abstract: | 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. |
| Keywords: | Indenoisoquinoline derivatives Anti-angiogenesis HIF-1α |
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