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Elbatrawy, Ahmed A ; Ademoye, Taiwo A ; Alnakhala, Heba ; Tripathi, Arati ; Zhu, Xiongwei ; Plascencia-Villa, Germán , et al.
Abstract: Alzheimer’s (AD) and Parkinson’s (PD) disease are neurodegenerative disorders that are considered to be a significant global health challenge due to their increasing prevalence and profound impact on both individuals and society. These disorders are characterized by the progressive loss of neuronal function, leading to cognitive and motor impairments. A key pathological feature of AD and PD is the abnormal accumulation of misfolded proteins within the brain. In AD, amyloid-beta aggregates into plaques, while tau proteins form neurofibrillary tangles (NFTs). Parkinson’s disease, on the other hand, is marked by the accumulation of α-synuclein (α-syn) in the form of Lewy bodies (LBs). These protein aggregates are involved in neuronal dysfunction and neurodegeneration, contributing to disease progression. Research efforts are increasingly focused on identifying small molecules that can simultaneously target multiple pathological processes, offering the potential to not only alleviate symptoms but also modify the progression of neurodegeneration. Herein, a novel group of triazole-based compounds was designed and synthesized to curtail the aggregation of α-syn and tau proteins, which are closely linked to the physiopathology of PD and AD, respectively. A thioflavin T (ThT) fluorescence assay was used to measure fibril formation and assess the antiaggregation effects of various compounds. To further validate these findings, transmission electron microscopy (TEM) was employed as a direct method to visualize the impact of these compounds on fibril morphology. Inhibition of oligomer formation was evaluated using photoinduced cross-linking of unmodified proteins (PICUP), enabling the detection of early protein aggregation events. During fibril formation assays, three compounds (3e, 4b, 4d) demonstrated superior inhibitory activity as assessed by ThT fluorescence and TEM imaging. Subsequent evaluations, which included tests for antioligomer, anti-inclusion, and disaggregation effects identified compound 4d as the most promising candidate overall.
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Purchased from AmBeed: 16066-91-4 ; 7758-99-8 ; 13965-03-2
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CAS No. : | 7758-99-8 |
Formula : | CuH10O9S |
M.W : | 249.69 |
SMILES Code : | O=S([O-])([O-])=O.[H]O[H].[H]O[H].[H]O[H].[H]O[H].[H]O[H].[Cu+2] |
MDL No. : | MFCD00149681 |
InChI Key : | JZCCFEFSEZPSOG-UHFFFAOYSA-L |
Pubchem ID : | 24463 |
GHS Pictogram: | ![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H318-H410 |
Precautionary Statements: | P264-P270-P273-P280-P301+P312+P330-P305+P351+P338+P310-P391-P501 |
Class: | 9 |
UN#: | 3077 |
Packing Group: | Ⅲ |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium chloride; sodium nitrite; In water; | A. Preparation of Ethyl 3-Chloro-1-methylpyrazole-4-carboxylate A solution of 41.4 g (267 mmol) of <strong>[21230-43-3]ethyl 3-amino-1-methylpyrazole-4-carboxylate</strong> in a mixture of 150 mL of concentrated hydrochloric acid, 50 mL of 85 percent phosphoric acid, and 100 mL of water was prepared and cooled to about 0 C. A solution of 18.6 g (270 mmol) of sodium nitrite in 50 mL of water was added to this dropwise with cooling and stirring. After a short time the reaction mixture was added dropwise with stirring at ambient temperature to a solution of 46.5 g (484 mmol) of cupric sulfate and 60.0 g (1.03 mol) of sodium chloride in 200 mL of water. When the addition was complete, the mixture was heated to 50 C. with stirring for 1 hr. A solid formed. The mixture was extracted with methylene chloride and the extract was washed with water, dried over magnesium sulfate, and concentrated by evaporation under reduced pressure to obtain an impure solid. This was dried and recrystallized from ethanol to obtain 24.8 g of the title compound as a white solid melting at 76-77 C. Elemental Analysis: Calc. for C7 H9 ClN2 O2: %C, 44.6; %H, 4.81: %N, 14.9 Found: %C, 45.6: %H, 5.11; %N, 15.4 1 H NMR Spectrum: (delta ppm from TMS) 7.8 (s, 1H), 4.26 (q, 2H, J=7.2), 3.83 (s, 3H), and 1.31 (t, 3H, J=7.2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In water; at 350.0℃; for 0.0666667h;Inert atmosphere; Sealed tube; | Using a 50 mL volumetric flask, 1.208 g of copper sulfate as a metal salt was dissolved in 50 mL of distilled water to prepare a 0.1 mol / L CuSO 4 aqueous solution. Next, 0.02 g (3.3 × 10 -5 mol) of tetraphenylporphyrin (TPP) as a compound having a porphyrin-type skeleton, 0.02 g (3.3 × 10 -5 mol) of copper sulfate Aqueous solution of sodium carbonate and 0.032 g of sodium carbonate equivalent to copper sulfate to prevent corrosion of the reaction vessel, and the interior of the reaction vessel was purged with argon and sealed. Next, the reaction vessel was charged into the sand bath set at 350 C. The reaction temperature in the reaction vessel reached the reaction temperature in about 4 minutes. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With cetyltrimethylammonim bromide;Inert atmosphere; | The reactions were carried out in three-necked glass-stopper flasksfitted with a double-surface water condenser (to arrest evaporation).The flask was kept in an oil-bath thermostated at the desired temperature.The required volumes of glycylphenylalanine, copper sulfate andCTAB (when required) were taken in the flask. A slow steam of purifiedN2 was flowed through the mixture to provide stirring and inert environment.The reaction was charged with the addition of requisite volume ofthermally equilibrated ninhydrin solution. The zero time was notedwhen half of the ninhydrin solution was added. The rate of formation of productwas followed using single beam UV-Vis spectrophotometer (withpath length of cuvette 1 cm) (SHIMADZU-model UV mini 1240, Kyoto,Japan) by pipetting out aliquots at known time intervals by monitoringabsorbance at lambdamax (=400 nm) (Fig. 1). During all kinetic runs, pseudofirst-order conditions were maintained by keeping [ninhydrin] in excess.The first-order rate constants in aqueous (kobs, s-1) and CTAB (kpsi, s-1)were calculated up to completion of 80% of the reaction by using a computerprogram. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; water; at 120 - 180℃; | 1.0 mmol of CuSO4 and 0.5 mmol of 2,2 ':6',2"-terpyridine-4'-carboxylic acid were mixed, and placed in a stainless steel-lined stainless steel reactor. 20 mL of deionized water and 10 mL of absolute ethanol were added, mixed evenly, sealed, and hydrothermal reaction was carried out at 120-180 ° C for 3 ~ 5 days under high temperature and high pressure environment to increase the reaction. The oxidation-reduction potential of the material changes significantly to improve the reaction rate. After completion of the hydrothermal reaction, the stainless steel reactor was cooled to room temperature by 5 ° C per hour to obtain a blue block of 2,2 ': 6', 2 'tripyridine-4'-carboxylic acid copper sulfate crystals. The resulting crystals were ground to 100 mesh sieve, to obtain terpyridine-4 '-carboxylic acid copper hydrogensulfate monoclinic blue powder having purity of not less than 99percent. |
Tags: 7758-99-8 synthesis path| 7758-99-8 SDS| 7758-99-8 COA| 7758-99-8 purity| 7758-99-8 application| 7758-99-8 NMR| 7758-99-8 COA| 7758-99-8 structure
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