title: Synthesis and evaluation of trehalose-based compounds as novel inhibitors of cancer cell migration and invasion.
abstract: As a continuous research for the discovery of trehalose-based anti-invasive agents, we developed a convenient synthetic approach for the preparation of 6,6'-dideoxy-6,6'-bis(acylamino)-α,α-D-trehaloses. A series of trehalose-based amides were prepared through the trityl protection of the two primary hydroxyls of α,α-D-trehalose, benzoylation, the removal of the trityl protective group, mesylation, azidation, catalytic hydrogenation in the presence of hydrochloride, coupling reaction with a variety of acids, and subsequent debenzoylation and deacetylation in some cases. Compound 8b, 6,6'-dideoxy-6,6'-bis(2-hydroxybenzamide)-α,α-D-trehalose, was just as potent as the natural brartemicin against the invasion of murine colon 26-L5 cells. It exhibited no cytotoxicity on human breast adenocarcinoma MDA-MB-231 and murine colon 26-L5 cells. It can significantly inhibit the migration and invasion of the MDA-MB-231 cells. The anti-invasive effect of 8b was possibly related to its inhibitory activity on MMP-9, its suppression on the expression of MMP-9 and VEGF, and its deactivation of Akt.
authors: Institute of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China.
authors: Yong-Li
authors: YL
authors: Jiang
authors: Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China.
authors: Shui-Xian
authors: SX
authors: Li
authors: Institute of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China.
authors: Yu-Jing
authors: YJ
authors: Liu
authors: Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China.
authors: Lian-Ping
authors: LP
authors: Ge
authors: Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China.
authors: Xiu-Zhen
authors: XZ
authors: Han
authors: Institute of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China.
authors: Zhao-Peng
authors: ZP
authors: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014199:Trehalose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D014199:Trehalose; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9
keywords: Akt; Brartemicin; MMP-9; VEGF; anti-invasive; metastasis; migration; trehalose