title: Novel chalcone derivatives as hypoxia-inducible factor (HIF)-1 inhibitor: synthesis, anti-invasive and anti-angiogenic properties.
abstract: 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.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China; Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China; Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Shanghe
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China; Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Guanfang
authors.initials: G
authors.lastname: Ping
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China; Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China; Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Huahuan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China; Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: yangjingyu2006@gmail.com.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China; Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: wucf@syphu.edu.cn.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Wu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D002599:Chalcone
keywords: Angiogenesis; Cancer; Chalcone; Hypoxia-inducible factor-1; Invasion