Synthesis and Evaluation of Trehalose‐Based Compounds as Novel Inhibitors of Cancer Cell Migration and Invasion |
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Authors: | Yu‐Jing Liu Lian‐Ping Ge Xiu‐Zhen Han Zhao‐Peng Liu |
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Institution: | 1. Institute of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China;2. Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, China |
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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. |
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Keywords: | Akt anti‐invasive Brartemicin metastasis migration MMP‐9 trehalose
VEGF
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