Biflavones inhibit the fibrillation and cytotoxicity of the human islet amyloid polypeptide

Abstract

Biflavones are a kind of natural compounds with a variety of biological activities, which have the effects of reversing diabetes and neurodegenerative diseases. Human islet amyloid polypeptide (hIAPP) is closely...

β‐Carboline Alkaloids Resist the Aggregation and Cytotoxicity of Human Islet Amyloid Polypeptide

“…The close contacts of non‐polar residues with β‐carbolines demonstrate the importance of hydrophobic interactions in the binding process. Besides, the contact probability of harmine with Phe23 reached 77.6 %, implying a possible π‐π stacking that contributed to the interactions [10,22] …”

“…The presence of small molecules seemed to disperse the folded octamer into a looser state, suggesting the influence of small molecules on peptide conformation. [10] The Ramachandran diagram can help identify whether the dihedral angles of amino acids are distributed within the structurally sound region of the peptides. [62,63] According to Figure 7A-C and Table S4, the residues of octamer alone completely fall within the maximum allowed region (the red region in Figure 7A).…”

“…The mechanism of hIAPP aggregation is reported by many studies, and the potential inhibitors, such as short peptides, natural products and metal complexes, are extensively investigated against amyloid fibril formation of hIAPP. [9][10][11][12][13][14][15] Natural products are a promising source of inhibitors, as they have made great contributions to the treatment of some serious diseases, especially cancer and infectious diseases. [16] Besides, natural compounds are more accessible, efficient and less toxic than conventional synthetic small molecules.…”

Illustrating the Effect of Small Molecules Derived from Natural Resources on Amyloid Peptides

“…On the other hand, hydrophobic interactions play a major role in EGCG-Aβ binding . Apigenin is also an effective inhibitor of α-syn aggregation and inhibits hIAPP fibril formation. , Biflavonoids with double apigenin structures (amentoflavone and bilobetin) display better inhibitory ability against hIAPP aggregation . Other natural flavonoids such as genistein, isorhamnetin, kaemferol, morin, myricetin, quercetin, rhamnazin, and tamarixetin share a similar scaffold but differ in the number and position of −OH and −OCH 3 groups (Figure ).…”

“…36,37 Biflavonoids with double apigenin structures (amentoflavone and bilobetin) display better inhibitory ability against hIAPP aggregation. 38 Other natural flavonoids such as genistein, isorhamnetin, kaemferol, morin, myricetin, quercetin, rhamnazin, and tamarixetin share a similar scaffold but differ in the number and position of −OH and −OCH 3 groups (Figure 5). 15,19,39 Most of these compounds exhibit similar capacity to inhibit Aβ aggregation and disassemble the preformed fibrils.…”