Discovery of New Inhibitors to Attenuate Migratory Capability of Colon Cancer Cells by the Drug Repositioning Strategy.

Recent studies revealed that intestinal microbiota played important roles in colorectal cancer (CRC) carcinogenesis. Particularly, was confirmed to promote the proliferation and metastasis of CRC. Therefore, targeting may be a potential preventive and therapeutic approach for CRC. Herein, 2,272 off-patent drugs were screened inhibitory activity against . Among the hits, nitisinone was identified as a promising anti- lead compound. Further optimization of nitisinone led to the discovery of more potent derivatives. Particularly, compounds and showed potent anti- activity (MIC = 1 and 2 μg/mL, respectively) with low cytotoxicity. Among them, compound effectively attenuated the migratory ability of MC-38 cells induced by . Preliminary mechanism studies suggested that nitisinone and its derivatives might act by downregulating nitroreductase and tryptophanase. Thus, the development of small molecule inhibitors represents an effective strategy to treat CRC.