Synthesis and Evaluation of a Novel Small-molecule Compound as an Anticancer Inhibitor of CD147

Objective Cancer is a serious threat to human health. Despite extensive research on cancer treatment,there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whether cancer cell malignancy is affected by CD147 expression level. The first compound(AC-73) targeting CD147 could only act on advanced tumors and inhibit metastasis. Therefore, new compounds with better anticancer activity should be explored.Methods Wst-1 assays were used to confirm the effect of novel compounds on proliferation.Apoptosis tests were used to evaluate their proapoptotic capacity. A nude mouse model was used to demonstrate in vivo anticancer activity and safety of the compounds. Western blots were used to suggest a molecule mechanism.Results There is a positive correlation between CD147 expression and tumor cell proliferation. A new compound, HA-08, was synthesized and proved to be more active than AC-73. HA-08 could inhibit cancer cell viability and promote cancer cell apoptosis both in vitro and in vivo. HA-08 induces cancer apoptosis, mainly by disrupting the CD147-CD44 interaction and then down-regulating the JAK/STAT3/Bcl-2 signaling pathway.Conclusion Our results have clarified the tumor specificity of CD147 and its drug target characteristics.The biological profile of HA-08 suggests that this compound could be developed as a potential anticancer agent.     

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