Synthesis and evaluation of N-(benzofuran-5-yl)aromaticsulfonamide derivatives as novel HIF-1 inhibitors that possess anti-angiogenic potential. Issue 6 (15th March 2017)

• Record Type: Journal Article
• Authors: Wei, Jinlian; Yang, Yingrui; Li, Yali; Mo, Xiaofei; Guo, Xiaoke; Zhang, Xiaojin; Xu, Xiaoli; Jiang, Zhengyu; You, Qidong
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 6(2017)
• Page Start: 1737
• Page End: 1746
• Publication Date: 2017-03-15
• Subjects: N-(Benzofuran-5-yl)aromaticsulfonamide derivatives -- HIF-1 -- Transcriptional activity -- Migration -- Anti-angiogenesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.06.021
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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 ± 0.7 μM) and secretion of VEGF (IC50 = 18.8 μM) 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 compound7q 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.