期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 186, 期 -, 页码 60-69出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2018.05.006
关键词
hIAPP; Schiff base oxovanadium complexes; Fibrillation; Interaction; Disaggregation
资金
- National Natural Science Foundation of China [21473251]
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)center dot H2O (1, and ligand 1 H2bhbb, 2-(5-bromo-2-hydro-xylbenzylideneamino) benzoic acid), VO(nhbb)center dot H2O (2, and lignad 2 H2nhbb, 2-(5-nitro-2-hydro-xylbenzylideneamino) 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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