Inhibitory effects of oxidovanadium complexes on the aggregation of human islet amyloid polypeptide and its fragments.

Human islet amyloid polypeptide (hIAPP) is synthesized by pancreatic β-cells and co-secreted with insulin. Misfolding and amyloidosis of hIAPP induce β-cell dysfunction in type II diabetes mellitus. Numerous small organic molecules and metal complexes act as inhibitors against amyloid-related diseases, justifying the need to explore the inhibitory mechanism of these compounds. In this work, three oxidovanadium complexes, namely, (NH)[VO(O)(bipy)]·4HO (1) (bipy = 2,2' bipyridine), bis(ethyl-maltolato, O,O)oxido-vanadium(IV) (2), and (bipyH)H[O{VO(O)(bipy)}]·5HO (3), were synthesized and used to inhibit the aggregation of hIAPP and its fragments, namely, hIAPP19-37 and hIAPP20-29. Results revealed that shortening the peptide sequence decreased the aggregation capability of hIAPP fragments, and the oxidovanadium complexes inhibited the fibrillization of hIAPP better than its fragments. Interestingly, the binding of oxidovanadium complexes to hIAPP and its fragments presented a distinct thermodynamic behavior. Oxidovanadium complexes featured the disaggregation capability against hIAPP, better than against its fragments. These complexes also decreased the cytotoxicity caused by hIAPP and its fragments by reducing the production of oligomers. 3 may be a good hIAPP inhibitor based on its inhibition, disaggregation capability, and regulatory effect on peptide-induced cytotoxicity. Oxidovanadium complexes exhibit potential as metallodrugs against amyloidosis-related diseases.