title: Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy.
abstract: A series of new (-)-arctigenin derivatives with variably modified O-alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC(50), 0.49 μM), diethoxy derivative 4h (PC(50), 0.66 μM), and triethoxy derivative 4m (PC(50), 0.78 μM) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (-)-arctigenin (1) (PC(50), 0.80 μM). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (-)-arctigenin (1). These results would suggest that a modification of (-)-arctigenin structure could lead to a new drug based on the antiausterity strategy.
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kudou
authors.forename: Akira
authors.initials: A
authors.lastname: Taniguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuya
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Toyooka
authors.forename: Chika
authors.initials: C
authors.lastname: Miyoshi
authors.forename: Suresh
authors.initials: S
authors.lastname: Awale
authors.forename: Dya Fita
authors.initials: DF
authors.lastname: Dibwe
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Esumi
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kadota
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tezuka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; 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: D000970:Antineoplastic Agents; D005663:Furans; D017705:Lignans; C071942:arctigenin