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.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Xiaoli
X
Xu
Fang
F
Liu
Shengmiao
S
Zhang
Jianmin
J
Jia
Zhiyu
Z
Li
Xiaoke
X
Guo
Yong
Y
Yang
Haopeng
H
Sun
Qidong
Q
You
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007192:Indenes / Q000737:chemistry / Q000494:pharmacology*; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015053:Zygote / Q000187:drug effects / Q000648:ultrastructure
D020533:Angiogenesis Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007192:Indenes; D007546:Isoquinolines; D059004:Topoisomerase I Inhibitors
Anti-angiogenesis; HIF-1α; Indenoisoquinoline derivatives