Discovery of 1,5-diaryl-1,2,4-triazole derivatives as myoferlin inhibitors and their antitumor effects in pancreatic cancer

摘要

Aim: The first inhibitor targeting myoferlin (MYOF), WJ460, bears poor metabolic stability and water solubility. Therefore, this study aimed to improve the druglike properties of WJ460. Materials & methods: The authors synthesized an array of 1,5-diaryl-1,2,4-triazole analogs and appraised the binding activities with MYOF and their antiproliferative and antimigratory activities against pancreatic cancer cells. Results: Molecular docking and surface plasmon resonance results showed that E4 was directly bound to the MYOF-C2D domain. E4 effectively inhibited the proliferation and migration of pancreatic cancer cells in vitro. In silico study suggested that the water solubility of E4 was improved by about 22-times than that of WJ460. Conclusion: The findings suggested that the druglike ability of E4 was significantly improved.

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