Abstract |
Two analogues possessing steric hindered substituents on C-15 of arenastatin A (1), a potent cytotoxic spongean depsipeptide, were synthesized and shown to enhance stability in mouse serum. Notably, 15-tert-butylanalogue (6) with higher cytotoxicity exhibited in vivo anti- tumor activity through iv administration different from 1. Additionally, conformation analysis among the two analogues and arenastatin A (1) indicated that the torsion angle from C-14 to C-20 is a conclusive factor for the potent cytotoxicity of 1.
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Authors | Nobutoshi Murakami, Satoru Tamura, Kouhei Koyama, Masanori Sugimoto, Ryuji Maekawa, Motomasa Kobayashi |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 14
Issue 10
Pg. 2597-601
(May 17 2004)
ISSN: 0960-894X [Print] England |
PMID | 15109660
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Cytotoxins
- Depsipeptides
- arenastatin A
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Topics |
- Animals
- Antineoplastic Agents
(administration & dosage, chemical synthesis)
- Carcinoma, Lewis Lung
(drug therapy)
- Cytotoxins
- Depsipeptides
(administration & dosage, chemical synthesis, therapeutic use)
- Dose-Response Relationship, Drug
- Drug Stability
- Mice
- Molecular Conformation
- Porifera
(chemistry)
- Structure-Activity Relationship
- Treatment Outcome
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