title: Structure-Activity Relationship and in Vivo Anti-Tumor Evaluations of Dictyoceratin-A and -C, Hypoxia-Selective Growth Inhibitors from Marine Sponge.
abstract: Oral dictyoceratin-C (1) and A (2), hypoxia-selective growth inhibitors, showed potent in vivo antitumor effects in mice subcutaneously inoculated with sarcoma S180 cells. Structurally modified analogs were synthesized to assess the structure-activity relationship of the natural compounds 1 and 2 isolated from a marine sponge. Biological evaluation of these analogs showed that the exo-olefin and hydroxyl and methyl ester moieties were important for the hypoxia-selective growth inhibitory activities of 1 and 2. Thus far, only substitution of the methyl ester with propargyl amide in 1 was found to be effective for the synthesis of probe molecules for target identification.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan. y-sumii@phs.osaka-u.ac.jp.
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. 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. sukoshi1293fushigi@yahoo.co.jp.
authors.forename: Akinori
authors.initials: A
authors.lastname: Fukuda
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan. pabro-ai@hotmail.co.jp.
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. araim@phs.osaka-u.ac.jp.
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. kobayasi@phs.osaka-u.ac.jp.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D062385:Hydroxybenzoates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D011161:Porifera / Q000378:metabolism; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000473:pathology; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D062385:Hydroxybenzoates; D012717:Sesquiterpenes; C493697:dictyoceratin-C; C000595511:smenospondiol
keywords: analog synthesis; dictyoceratin-A; dictyoceratin-C; hypoxia-selective growth inhibitor; in vivo antitumor effect; marine sponge; structure-activity relationship