Synthesis and evaluation of trehalose-based compounds as anti-invasive agents.

Abstract

Brartemicin is a trehalose-based inhibitor of tumor cell invasion produced by the actinomycete of the genus Nonomuraea. In order to explore the preliminary structure-activity relationship and obtain more potent inhibitors, a series of brartemicin analogs were synthesized through the Mitsunobu coupling of the secondary hydroxyls benzyl protected α,α-D-trehalose with benzoic acid derivatives, followed by modification of functional groups and deprotection. These compounds were evaluated for their inhibitory activity against invasion of murine colon 26-L5 carcinoma cells in vitro. Among the synthetic analogs tested, 6,6'-bis(2,3-dimethoxybenzoyl)-α,α-D-trehalose (5e) was found to be the most potent anti-invasive agent, exhibited a 2.6-fold improvement with regard to the parent natural product brartemicin, and it is considered to be a promising lead molecule for the anti-metastasis.

• Authors: Yong-Li Jiang, Long-Qian Tang, Satoshi Miyanaga, Yasuhiro Igarashi, Ikuo Saiki, Zhao-Peng Liu
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 21 Issue 4 Pg. 1089-91 (Feb 15 2011) ISSN: 1464-3405 [Electronic] England
• PMID: 21269828 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• 6,6'-bis(2,3-dimethoxybenzoyl)-alpha,alpha-trehalose
• Antineoplastic Agents
• brartemicin
• Trehalose

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, therapeutic use)
• Cell Line, Tumor
• Mice
• Structure-Activity Relationship
• Trehalose (analogs & derivatives, chemical synthesis, chemistry, therapeutic use)