title: Synthesis of 15,20-triamide analogue with polar substituent on the phenyl ring of arenastatin A, an extremely potent cytotoxic spongean depsipeptide.
abstract: In order to increase metabolic stability and water solubility of arenastatin A, an extremely potent cytotoxic depsipeptide from the Okinawan marine sponge of Dysidea arenaria, several 15,20-triamide analogues with a polar substituent on the phenyl ring were synthesized. The 15,20-triamide analogues with a polar substituent (24, 30, and 31) showed increased solubility to MeOH and stronger cytotoxicity against KB cells in comparison with the parental 15,20-triamide analogue (2). Furthermore, the diethylamine analogue (30) exhibited in vivo anti-tumor activity against subcutaneously implanted murine sarcoma.
authors.affiliation: Department of Natural Product Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kotoku
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kato
authors.forename: Fuminori
authors.initials: F
authors.lastname: Narumi
authors.forename: Emiko
authors.initials: E
authors.lastname: Ohtani
authors.forename: Sayo
authors.initials: S
authors.lastname: Kamada
authors.forename: Shunji
authors.initials: S
authors.lastname: Aoki
authors.forename: Naoki
authors.initials: N
authors.lastname: Okada
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Motomasa
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000577:Amides / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047630:Depsipeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D047088:Dysidea / Q000737:chemistry*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D047630:Depsipeptides; C096566:arenastatin A