title: Synthesis and evaluation of effective photoaffinity probe molecule of furospinosulin-1, a hypoxia-selective growth inhibitor.
abstract: The synthesis and evaluation of a photoaffinity probe molecule for furospinosulin-1, a hypoxia-selective growth inhibitor that we identified from marine sponge, was studied. An analogue carrying an alkyne tail showed potent hypoxia-selective inhibitory activity exceeding that of the parent molecule, and exhibited in vivo anti-tumor activity following oral administration. The alkyne moiety in the analogue was also found to be a good anchoring group for the preparation of probe molecules; a photoaffinity probe molecule having an optimized spacer length was selected through the systematic synthesis of several probes and the evaluation of their hypoxia-selective growth inhibitory activity and electrophoretic mobility shift properties.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan. Electronic address: kotoku@phs.osaka-u.ac.jp.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kotoku
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakata
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawachi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Sato
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Xiu-Han
authors.initials: XH
authors.lastname: Guo
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Ito
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sumii
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Arai
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan. Electronic address: kobayasi@phs.osaka-u.ac.jp.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D000860:Hypoxia; D051379:Mice; D015394:Molecular Structure; D019920:Photoaffinity Labels / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054830:Sesterterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D019920:Photoaffinity Labels; D054830:Sesterterpenes; C555679:furospinosulin-1
keywords: Analogue compound; Furospinosulin-1; Hypoxia-selective growth inhibitor; Marine sponge; Photoaffinity probe