• Yong-Li Jiang, Long-Qian Tang, Satoshi Miyanaga, Yasuhiro Igarashi, Ikuo Saiki, and Zhao-Peng Liu.
• School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhua Xilu, Jinan 250012, Shandong Province, PR China.
• Bioorg. Med. Chem. Lett. 2011 Feb 15; 21 (4): 1089-91.

AbstractBrartemicin 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.Copyright © 2011 Elsevier Ltd. All rights reserved.

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