Synthesis of 15,20-triamide analogue with polar substituent on the phenyl ring of arenastatin A, an extremely potent cytotoxic spongean depsipeptide.
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.
Kotoku
Naoyuki
N
Department of Natural Product Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
Kato
Tomoya
T
Narumi
Fuminori
F
Ohtani
Emiko
E
Kamada
Sayo
S
Aoki
Shunji
S
Okada
Naoki
N
Nakagawa
Shinsaku
S
Kobayashi
Motomasa
M
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
D000577:Amides; D000970:Antineoplastic Agents; D047630:Depsipeptides; C096566:arenastatin A