1. Discovery of 1,5-diaryl-1,2,4-triazole derivatives as myoferlin inhibitors and their antitumor effects in pancreatic cancer
- Author
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Haijun Gu, Ting Zhang, Yunqi Li, Yuan He, Tian Guan, Weiqiong Kan, Peng He, Zhengfang Yi, and Yihua Chen
- Subjects
Pharmacology ,Calcium-Binding Proteins ,Muscle Proteins ,Membrane Proteins ,Water ,Antineoplastic Agents ,Molecular Docking Simulation ,Pancreatic Neoplasms ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,Humans ,Molecular Medicine ,Cell Proliferation - Abstract
Aim: The first inhibitor targeting myoferlin (MYOF), WJ460, bears poor metabolic stability and water solubility. Therefore, this study aimed to improve the drug-like 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. An 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.
- Published
- 2022