New analogue of arenastatin A, a potent cytotoxic spongean depsipeptide, with anti-tumor activity

Nobutoshi Murakami; Satoru Tamura; Kouhei Koyama; Masanori Sugimoto; Ryuji Maekawa; Motomasa Kobayashi

doi:10.1016/j.bmcl.2004.02.080

New analogue of arenastatin A, a potent cytotoxic spongean depsipeptide, with anti-tumor activity

Bioorg Med Chem Lett. 2004 May 17;14(10):2597-601. doi: 10.1016/j.bmcl.2004.02.080.

Authors

Nobutoshi Murakami¹, Satoru Tamura, Kouhei Koyama, Masanori Sugimoto, Ryuji Maekawa, Motomasa Kobayashi

Affiliation

¹ Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.

PMID: 15109660
DOI: 10.1016/j.bmcl.2004.02.080

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / chemical synthesis*
Carcinoma, Lewis Lung / drug therapy
Cytotoxins
Depsipeptides / administration & dosage*
Depsipeptides / chemical synthesis
Depsipeptides / therapeutic use
Dose-Response Relationship, Drug
Drug Stability
Mice
Molecular Conformation
Porifera / chemistry
Structure-Activity Relationship
Treatment Outcome

Substances

Antineoplastic Agents
Cytotoxins
Depsipeptides
arenastatin A