2. Academic Validation
  3. Synthesis and evaluation of N-(benzofuran-5-yl)aromaticsulfonamide derivatives as novel HIF-1 inhibitors that possess anti-angiogenic potential

Synthesis and evaluation of N-(benzofuran-5-yl)aromaticsulfonamide derivatives as novel HIF-1 inhibitors that possess anti-angiogenic potential

  • Bioorg Med Chem. 2017 Mar 15;25(6):1737-1746. doi: 10.1016/j.bmc.2016.06.021.
Jinlian Wei 1,  Yingrui Yang 1,  Yali Li 1,  Xiaofei Mo 1,  Xiaoke Guo 1,  Xiaojin Zhang 2,  Xiaoli Xu 1,  Zhengyu Jiang 1,  Qidong You 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
  • 2 State Key Laboratory of Natural Medicines, and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; Department of Organic Chemistry, School of Science, China Pharmaceutical University, Nanjing 210009, China.
  • 3 State Key Laboratory of Natural Medicines, and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: youqd@163.com.
PMID: 28209257 DOI: 10.1016/j.bmc.2016.06.021
Abstract

Hypoxia-inducible factor-1 (HIF-1) as a key mediator in tumor metastasis, angiogenesis, and poor patient prognosis has been recognized as an important Cancer drug target. A novel series of N-(benzofuran-5-yl)aromaticsulfonamide derivatives were synthesized and evaluated as HIF-1 inhibitor. Among these compounds, 7q exhibited specific inhibitory effects on HIF-1 by downregulating the expression of HIF-1α under hypoxic conditions. It inhibited the HIF-1 transcriptional activity (IC50=12.5±0.7μM) and secretion of VEGF (IC50=18.8μM) in MCF-7 cells. Meanwhile, it also significantly suppressed hypoxia-induced migration of HUVEC cells in nontoxic concentrations. Additionally, tube formation assay demonstrated its anti-angiogenesis activity. Finally, the in vivo study indicated that compound 7q could retard angiogenesis in CAM model. These findings supported the HIF-1 inhibitory effect and anti-angiogenic potential of this class of compounds as HIF-1 inhibitor.

Keywords

Anti-angiogenesis; HIF-1; Migration; N-(Benzofuran-5-yl)aromaticsulfonamide derivatives; Transcriptional activity.

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