Synthesis of 15,20-triamide analogue with polar substituent on the phenyl ring of arenastatin A, an extremely potent cytotoxic spongean depsipeptide

Naoyuki Kotoku; Tomoya Kato; Fuminori Narumi; Emiko Ohtani; Sayo Kamada; Shunji Aoki; Naoki Okada; Shinsaku Nakagawa; Motomasa Kobayashi

doi:10.1016/j.bmc.2006.07.019

Synthesis of 15,20-triamide analogue with polar substituent on the phenyl ring of arenastatin A, an extremely potent cytotoxic spongean depsipeptide

Bioorg Med Chem. 2006 Nov 15;14(22):7446-57. doi: 10.1016/j.bmc.2006.07.019. Epub 2006 Jul 31.

Authors

Naoyuki Kotoku¹, Tomoya Kato, Fuminori Narumi, Emiko Ohtani, Sayo Kamada, Shunji Aoki, Naoki Okada, Shinsaku Nakagawa, Motomasa Kobayashi

Affiliation

¹ Department of Natural Product Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.

PMID: 16877000
DOI: 10.1016/j.bmc.2006.07.019

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.

Publication types

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

MeSH terms

Amides / chemistry*
Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Cell Line
Cell Line, Tumor
Cell Proliferation / drug effects
Depsipeptides / chemical synthesis
Depsipeptides / chemistry*
Depsipeptides / toxicity*
Dysidea / chemistry*
Humans
Mice
Molecular Structure
Neoplasm Transplantation
Structure-Activity Relationship

Substances

Amides
Antineoplastic Agents
Depsipeptides
arenastatin A