title: 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.affiliation: School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhua Xilu, Jinan 250012, Shandong Province, PR China.
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Jiang
authors.forename: Long-Qian
authors.initials: LQ
authors.lastname: Tang
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyanaga
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Igarashi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Zhao-Peng
authors.initials: ZP
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D051379:Mice; D013329:Structure-Activity Relationship; D014199:Trehalose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use
chemical_list: C558286:6,6'-bis(2,3-dimethoxybenzoyl)-alpha,alpha-trehalose; D000970:Antineoplastic Agents; C550819:brartemicin; D014199:Trehalose