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European Journal of Medicinal Chemistry 2015-Jan

Novel chalcone derivatives as hypoxia-inducible factor (HIF)-1 inhibitor: synthesis, anti-invasive and anti-angiogenic properties.

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Lihui Wang
Guoliang Chen
Xiuhong Lu
Shuang Wang
Shanghe Han
Yi Li
Guanfang Ping
Xiaorui Jiang
Huahuan Li
Jingyu Yang

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A novel series of chalcone derivatives were synthesized and their biological activities against HIF-1 were evaluated. Among these compounds, 5d exhibited clearly inhibitory effects on HIF-1 by downregulating the expression of HIF-1α under hypoxic conditions. Meanwhile, it also significantly suppressed VEGF-induced migration and invasion of Hep3B and HUVEC cells in nontoxic concentrations. Additionally, tube formation assay demonstrated its anti-angiogenesis activity. Moreover, the in vivo study indicated that compound 5d could retard tumor growth of Hep3B xenograft models and reduced CD31 and MMP-2 expression in tumor tissues. Finally, in acute intravenous toxicity, 5d was well tolerated and was found to be non-toxic up to 200 mg/kg in Swiss mice. These findings support the further investigation on the anti-invasive and anti-angiogenic potential of this class of compounds as HIF-1 inhibitor.

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