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

Autor:	Haijun Gu, Ting Zhang, Yunqi Li, Yuan He, Tian Guan, Weiqiong Kan, Peng He, Zhengfang Yi, Yihua Chen
Rok vydání:	2022
Předmět:	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
Zdroj:	Future Medicinal Chemistry. 14:1425-1440
ISSN:	1756-8927 1756-8919
DOI:	10.4155/fmc-2022-0168
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::63ea21595438e5545809ee0867089a28 https://doi.org/10.4155/fmc-2022-0168 Zobrazit plný text záznamu