Insights into the inhibitory mechanism of a resveratrol and clioquinol hybrid against Aβ₄₂ aggregation and protofibril destabilization: A molecular dynamics simulation study

Destabilization potential of beta sheet breaker peptides on Abeta fibril structure: an insight from molecular dynamics simulation study

“…The U-shaped model (2BEG) has been part of most of the previously reported molecular simulation studies. [64][65][66][67][68][69][70] Thus, 2BEG model was selected for the study.…”

Protofibrils of Amyloid-β are Important Targets of a Disease-Modifying Approach for Alzheimer’s Disease

“…At this site, wgx-50 was observed to be packed against the side chains of I32 and L34, disrupting the D23-K28 salt bridge and partially opening the two tightly compacted β-sheets [53]. Recently, Saini et al reported that a resveratrol and clioquinol hybrid compound, (E)-5-(4-hydroxystyryl)quinolone-8-ol, inhibits Aβ 1-42 aggregation by preventing the conformational transition of the Aβ 1-42 monomer and causing destablization of the Aβ 1-42 PF structure using MD simulation [54]. The destabilizing mechanisms of the Aβ 1-42 PF structure may be due to the increasing interchain distance between chains A-B, disrupting the salt-bridge interaction between D23-K28 and decreasing the number of backbone hydrogen bonds between the chains [54].…”

“…Recently, Saini et al reported that a resveratrol and clioquinol hybrid compound, (E)-5-(4-hydroxystyryl)quinolone-8-ol, inhibits Aβ 1-42 aggregation by preventing the conformational transition of the Aβ 1-42 monomer and causing destablization of the Aβ 1-42 PF structure using MD simulation [54]. The destabilizing mechanisms of the Aβ 1-42 PF structure may be due to the increasing interchain distance between chains A-B, disrupting the salt-bridge interaction between D23-K28 and decreasing the number of backbone hydrogen bonds between the chains [54]. In the same year, it was reported that β-sheet breaker peptides, particularly PPFFE pentapeptides, display strong destablizing effects that shift the energy minima toward the lowest value of sheet content and the lowest number of hydrogen bonds in Aβ 1-42 PFs, using in silico methodologies including the molecular mechanics Poisson-Bolzmann surface area method and MD simulations [55].…”

Resveratrol targeting tau proteins, amyloid‐beta aggregations, and their adverse effects: An updated review

“…A hybrid of Res and clioquinol considerably suppresses the aggregation of Aβ (1–42) plaques. Besides, this hybrid disrupts and destabilizes the Aβ (1–42) protofibril structure via enhancing the interchain distance between chains A and B, interfering salt–bridge interaction, and diminishing the number of backbone hydrogen bonds (Saini, Shuaib, Goyal, & Goyal, 2019). The studies demonstrate that MTDLs of Res such as deferiprone‐Res, tacrine‐Res, and Res‐indazole have high neuroprotective impacts and can be considered as potential agents in the treatment of NDs due to their capability in suppressing Aβ aggregation (Jerabek et al, 2017; Lan et al, 2018; P. Xu, Zhang, Sheng, & Ma, 2017).…”