Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.

N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis. Glycosylated CD147 is highly expressed in various cancer types, participates in metastasis, and is associated with the poor prognosis of malignant tumors. However, to date, there has been little development of target-specific inhibitors for CD147 glycosylation. In this work, we report a strategy for discovering CD147 glycosylation inhibitors through computer-aided screening and inhibition assays. Four compounds were screened as potential CD147 glycosylation inhibitors. Of these, compound 72 was finally identified as the best candidate. Further experiments confirmed that compound 72 inhibited the production of MMPs and the metastasis of cancer cells in the Hela cell line. Results further suggest that compound 72 could promote the expression of E-cadherin by targeting CD147, thereby inhibiting tumor migration. Finally, the structures of the other potential CD147 N-glycosylation inhibitors may eventually provide guidance for future optimization.