Synthesis and Evaluation of Trehalose‐Based Compounds as Novel Inhibitors of Cancer Cell Migration and Invasion

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.