3 research outputs found
Molecular Dynamics Study on the Inhibition Mechanisms of Drugs CQ<sub>1–3</sub> for Alzheimer Amyloid‑β<sub>40</sub> Aggregation Induced by Cu<sup>2+</sup>
The
aggregation of amyloid-β (Aβ) peptide induced by Cu<sup>2+</sup> is a key factor in development of Alzheimer’s disease
(AD), and metal ion chelation therapy enables treatment of AD. Three
CQ<sub><i>i</i></sub> (i = 1, 2, and 3 with R = H, Cl, and
NO<sub>2</sub>, respectively) drugs had been verified experimentally
to be much stronger inhibitors than the pioneer clioquinol (CQ) in
both disaggregation of Aβ<sub>40</sub> aggregate and reduction
of toxicity induced by Cu<sup>2+</sup> binding at low pH. Due to the
multiple morphologies of Cu<sup>2+</sup>–Aβ<sub>40</sub> complexes produced at different pH states, we performed a series
of molecular dynamics simulations to explain the structural changes
and morphology characteristics as well as intrinsic disaggregation
mechanisms of three Cu<sup>2+</sup>–Aβ<sub>40</sub> models
in the presence of any of the three CQ<sub><i>i</i></sub> drugs at both low and high pH states. Three inhibition mechanisms
for CQ<sub><i>i</i></sub> were proposed as “insertion”,
“semi-insertion”, and “surface” mechanisms,
based on the morphologies of CQ<sub><i>i</i></sub>–model <i>x</i> (CQ<sub><i>i</i></sub>–<i>x</i>, <i>x</i> = 1, 2, and 3) and the strengths of binding
between CQ<sub><i>i</i></sub> and the corresponding model <i>x</i>. The insertion mechanism was characterized by the morphology
with binding strength of more than 100 kJ/mol and by CQ<sub><i>i</i></sub> being inserted or embedded into the hydrophobic
cavity of model <i>x</i>. In those CQ<sub><i>i</i></sub>–<i>x</i> morphologies with lower binding
strength, CQ<sub><i>i</i></sub> only attaches on the surface
or inserts partly into Aβ peptide. Given the evidence that the
binding strength is correlated positively with the effectiveness of
drug to inhibit Aβ aggregation and thus to reduce toxicity,
the data of binding strength presented here can provide a reference
for one to screen drugs. From the point of view of binding strength,
CQ<sub>2</sub> is the best drug. Because of the special role of Asp23
in both Aβ aggregation and stabilizing the Aβ fibril,
the generation of a H-bond between CQ<sub>3</sub> and Asp23 of the
Aβ<sub>40</sub> peptide is believed to be responsible for CQ<sub>3</sub> having the strongest disaggregation capacity. Therefore,
besides strong binding, stronger propensity to H-bond with Asp23 would
be another key factor to be taken seriously into account in drug screens.
Meanwhile, the structural characteristics of drug CQ<sub><i>i</i></sub> itself are also worthy of attention. First, the increasing
polarity from CQ<sub>1</sub> and CQ<sub>2</sub> to CQ<sub>3</sub> in
turn results in increasing probability and strength of the interaction
between the drug and the N-terminal (NT) region of Aβ<sub>40</sub>, which obviously inhibits Aβ peptide aggregation induced by
Cu<sup>2+</sup> binding. Second, both the benzothiazole ring and phenol
ring of CQ<sub><i>i</i></sub> can overcome the activation
energy barrier (∼16 kJ/mol) to rotate flexibly around the intramolecular
C7–N14 bond to achieve the maximum match and interaction with
the ambient Aβ<sub>40</sub> residues. Such a structural feature
of CQ<sub><i>i</i></sub> paves the new way for ones in selection
and modification of a drug
Synthesis of Cerium Molybdate Hierarchical Architectures and Their Novel Photocatalytic and Adsorption Performances
Cerium molybdate (Ce–Mo) hierarchical architectures (such as the flowerlike, microspheric, and bundlelike structure) are successfully synthesized via a facile route with the assistance of amino acid (lysine, Lys). The influences of reaction parameters on the crystal structure and morphology of Ce–Mo hierarchical architectures are investigated. Samples obtained are characterized using X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), Fourier transform infrared spectra (FT-IR), and thermogravimetric analysis (TGA). Furthermore, the photocatalytic and adsorption performances of samples obtained are investigated using different dyes, such as Cationic red X-GTL, Congo red, Methylene blue, Acid blue 80, and Methyl orange, as the model. The results show that Ce–Mo hierarchical architectures exhibit remarkably high efficiency to photocatalytically decompose Congo red under visible light irradiation, and significant adsorption performance on Cationic red X-GTL and Methylene blue. Contrarily, neither photocatalytic nor adsorption performance was observed on Methyl orange and Acid blue 80. Therefore, the as-synthesized Ce–Mo hierarchical architectures display promising potential for the removal of organic contaminants for environmental protection