title: Design, Synthesis and Structure-Activity Relationship Studies of Novel 4 (1-adamantyl) Phenyl Analogues as HIF-1α Inhibitors.
abstract: Hypoxia inducible factor-1 (HIF-1) is a key mediator during cancer cells to adapt tumor hypoxic condition. In this study, a series of adamantane-based compounds were synthesized and evaluated as potential inhibitors of HIF-1α. Examination of their structure-activity relationship (SAR) identified the adamantane-containing indole derivative 20a as a potent inhibitor of HIF-1α in Hep3B cell lines under tumor hypoxia (IC50 = 0.02 µM). The study herein may provide valuable information for the development of novel therapeutics against cancer and tumor angiogenesis.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.forename: Qiong
authors.initials: Q
authors.lastname: Duan
authors.forename: Bao-Hua
authors.initials: BH
authors.lastname: Zhao
authors.affiliation: Laboratory of Photoelectric Material, Advanced Institute of Materials Science, Changchun University of Technology, 130012, Changchun, P. R. China. lidongfeng@ccut.edu.cn.
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Li
authors.affiliation: Department of Chemistry, College of Chemistry and Life Science, Changchun University of Technology, 130012, Changchun, P. R. China. hrb1018@163.com.
authors.forename: Rui-Bin
authors.initials: RB
authors.lastname: Hou
mesh_terms: D000083:Acetanilides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D000072258:Tumor Hypoxia
chemical_list: D000083:Acetanilides; D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000621031:methyl 3-(2-(2-(3-(1H-indol-3-yl)acrylamido)-4-(adamantan-1-yl)phenoxy)acetamido)benzoate; D000218:Adamantane