Indenoisoquinoline derivatives as topoisomerase I inhibitors that suppress angiogenesis by affecting the HIF signaling pathway - 09/11/13

Doi : 10.1016/j.biopha.2013.06.004

Xiaoli Xu ^a,^b, Fang Liu ^a,^b, Shengmiao Zhang ^a,^b, Jianmin Jia ^a,^b, Zhiyu Li ^c, Xiaoke Guo ^a,^b, Yong Yang ^d, Haopeng Sun ^a,^b,^c,^⁎ , Qidong You ^a,^b,^⁎,^{^{1
Tel./fax: +86 25 83271351.}}
^a State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
^b Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China
^c Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China
^d Department of Physiology, School of Pharmacy, China Pharmaceutical University, Nanjing, China

^⁎Corresponding authors. China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China. Tel.:/fax: +86 25 83271216.

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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.

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Keywords : Indenoisoquinoline derivatives, Anti-angiogenesis, HIF-1α

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Vol 67 - N° 8

P. 715-722 - octobre 2013 Retour au numéro

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Indenoisoquinoline derivatives as topoisomerase I inhibitors that suppress angiogenesis by affecting the HIF signaling pathway - 09/11/13

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