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

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

Bioorg Med Chem. 2016 Jun 11;:

Authors: Wei J, Yang Y, Li Y, Mo X, Guo X, Zhang X, Xu X, Jiang Z, You Q

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.

PMID: 28209257 [PubMed - as supplied by publisher]

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