title: Synthesis and structure-activity relationships studies of brartemicin analogs 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 find more potent anti-invasive agents and study the structure-activity relationships, a series of 19 brartemicin analogs were prepared via two synthetic routes from α,α-D-trehalose and evaluated for their anti-invasive activities. Compound 4f, 6,6'-bis(2,3-dimethoxybenzoyl)-α,α-D-trehalose, was more potent than the natural brartemicin. It inhibited the invasion of murine colon 26-L5, colon carcinoma SW620, melanoma B16-BL6 and breast MDA-MB-231 cells with IC50 values of 0.15, 2.35, 4.12 and 2.61 μM, respectively. Analog 4p, 6,6'-bis(3,4-dimethoxycinnamoyl)-α,α-D-trehalose, was as potent as brartemicin against invasion of murine colon 26-L5 carcinoma cells in vitro. The structure-activity relationships of these novel trehalose-based compounds were summarized.
authors: Department of Organic Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors: Yong-Li
authors: YL
authors: Jiang
authors: Satoshi
authors: S
authors: Miyanaga
authors: Xiu-Zhen
authors: XZ
authors: Han
authors: Long-Qiang
authors: LQ
authors: Tang
authors: Yasuhiro
authors: Y
authors: Igarashi
authors: Ikuo
authors: I
authors: Saiki
authors: Zhao-Peng
authors: ZP
authors: Liu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014199:Trehalose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; C550819:brartemicin; D014199:Trehalose