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Schiff base oxovanadium complexes resist the assembly behavior of human islet amyloid polypeptide.
Xu, Jufei; Gong, Gehui; Huang, Xiangyi; Du, Weihong.
Afiliación
  • Xu J; Department of Chemistry, Renmin University of China, Beijing 100872, China.
  • Gong G; Department of Chemistry, Renmin University of China, Beijing 100872, China.
  • Huang X; Department of Chemistry, Renmin University of China, Beijing 100872, China.
  • Du W; Department of Chemistry, Renmin University of China, Beijing 100872, China. Electronic address: whdu@ruc.edu.cn.
J Inorg Biochem ; 186: 60-69, 2018 09.
Article en En | MEDLINE | ID: mdl-29857172
The misfolding and fibrillation of human islet amyloid polypeptide (hIAPP) is related to the pathologic process of type II diabetes mellitus (T2DM). The inhibitors of hIAPP aggregation include aromatic organic molecules, short peptides, and metal complexes. Vanadium complexes have been applied for the treatment of diabetes since the 19th century. However, the antidiabetes mechanism remains unclear. In this work, we used four Schiff base oxidovanadium(IV) complexes, namely VO(bhbb)·H2O (1, and ligand 1 H2bhbb, 2-(5-bromo-2-hydroxylbenzylideneamino) benzoic acid), VO(nhbb)·H2O (2, and lignad 2 H2nhbb, 2-(5-nitro-2-hydroxylbenzylideneamino) benzoic acid), VO(cpmp)2 (3, and ligand 3 Hcpmp, 4-chloro-2-(phenylimino) methyl) phenol), and VO(bpmp)2 (4, and ligand 4 Hbpmp, 4-bromo- 2-(phenylmino) methyl) phenol) to inhibit the fibril formation of hIAPP and reduce peptide-induced cytotoxicity. Results indicated that the four Schiff base oxidovanadium complexes effectively impeded hIAPP aggregation and disaggregated mature fibrils into monomers or oligomers. These V complexes also decreased hIAPP-induced cytotoxicity. Among the four V complexes, 1 is a promising candidate metallodrug considering its inhibitory effect, disaggregation ability, regulation of peptide-induced cytotoxicity, and binding affinity to the peptide. Our research provides a new outlook for the design of oxidovanadium complexes as effective inhibitors of hIAPP against T2DM.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vanadatos / Polipéptido Amiloide de los Islotes Pancreáticos / Agregado de Proteínas / Antidiarreicos Límite: Humans Idioma: En Revista: J Inorg Biochem Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vanadatos / Polipéptido Amiloide de los Islotes Pancreáticos / Agregado de Proteínas / Antidiarreicos Límite: Humans Idioma: En Revista: J Inorg Biochem Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos