Flavonoids with Vicinal Hydroxyl Groups Inhibit Human Calcitonin Amyloid Formation

Abstract

Humanc alcitonin (hCT) is a3 2-residue peptide hormone that can aggregate into amyloid fibrils and cause cellulart oxicity.I nt his study,w ei nvestigated the inhibition effects of ag roup of polyphenolic molecules on hCT amyloid formation. Our results suggest that the gallate moiety in epigallocatechin-3-gallate (EGCG), aw ell-recognized amyloid inhibitor,i sn ot criticalf or its inhibition function in the hCT amyloid formation. Ourr esults demonstrate that flavonoid compounds, such as myricetin, quercetin, and baicalein, that containv icinal hydroxyl groupso nt he phenyl ring effectively prevent hCT fibrillization. This structural feature may also be appliedt on on-flavonoidp olyphenolici nhibitors.M ore-over,o ur results indicate ap lausible mechanistic role of these vicinal hydroxylg roups which might include the oxidationto form aq uinone and the subsequent covalentl inkage with amino acid residuess uch as lysineo rh istidine in hCT.T his may furtherd isrupt the crucial electrostatic and aromatic interactions involved in the process of hCT amyloid fibril formation. The inhibition activity of the polyphenolic compounds against hCT fibril formationm ay likely be attributed to ac ombinationo ff actorss uch as covalentl inkage formation,aromatic stacking,a nd hydrogen bonding interactions.

Dopamine-Conjugated Carbon Dots Inhibit Human Calcitonin Fibrillation

“…Therefore, we speculated that DA-CDs might be capable of dissociating preformed aggregates since a difference in ThT intensity was consistently monitored from 32 h to the end of the reaction. Similar ThT curves are also observed when using flavonoids as hCT inhibitors [12].…”

“…More recently, a group of polyphenolic molecules were tested for their ability to inhibit hCT amyloid formation. The results suggested that the structural feature of the vicinal hydroxyl (catechol) group was essential for their ability in disrupting the process of fibril formation [ 12 ]. These studies may provide great help in drug design.…”

Combined in Silico and in Vitro Approaches To Uncover the Oxidation and Schiff Base Reaction of Baicalein as an Inhibitor of Amyloid Protein Aggregation

“…[4b] The presence of vicinal hydroxy groups on the phenyl rings of polyphenolic molecules is also reported as essential for their inhibitory activity against human calcitonin aggregation. [14] As observed for 1, both 2 a and 2 d have slightly nonplanar structures (torsion angles around the C2À C1' bond of 20.2°and 18.3°, respectively). In addition, both tautomers have intramolecular H bonds: in 2 a the C7À OH interacts with the carbonyl group of C6 (2.25 Å), whilst in 2 d the proton of O4 orients to the neighboring C5À O, establishing a short interaction (1.77 Å) that anticipates an easy interconversion between 2 d and 2 b tautomers.…”

Identification of Catechins Binding Pockets in Monomeric Aβ42Through Ensemble Docking and MD Simulations

“…Those studies have proposed that catechins are able to disturb the Aβ aggregation and induce its aggregation into nontoxic forms oligomers. 21,28,[71][72][73][74][75][76][77][78][79][80] In order to further evaluate the docking results and the stability of complexes, the obtained structures with the largest binding energies for each Aβ42-catechin complex were used as the starting structures for long multi-microsecond MD simulations (total of 15 μs).…”