Design, Synthesis, Molecular Docking, and Cholinesterase Inhibitory Potential of Phthalimide‐Dithiocarbamate Hybrids as New Agents for Treatment of Alzheimer's Disease

2019 ◽  
Vol 16 (11) ◽  
Author(s):  
Mehdi Asadi ◽  
Mostafa Ebrahimi ◽  
Maryam Mohammadi‐Khanaposhtani ◽  
Homa Azizian ◽  
Saghi Sepehri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
New Agents ◽  
Design Synthesis ◽  
Inhibitory Potential

Drug Design of Inhibitors of Alzheimer’s Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives

2019 ◽  
Vol 19 (8) ◽  
pp. 688-705
Author(s):  
Taibi Ben Hadda ◽  
Abdur Rauf ◽  
Hsaine Zgou ◽  
Fatma Sezer Senol ◽  
Ilkay Erdogan Orhan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Metal Accumulation ◽  
Microtiter Plate ◽  
Metal Chelation ◽  
Carbonyl Derivatives ◽  
Cholinesterase Inhibitory Activity ◽  
Inhibitory Potential

Background:Since deficit of acetylcholine has been evidenced in the Alzheimer’s disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD.Method:In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 μg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity.Results and Conclusion:All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good harmonization with experimental data.

scholarly journals Anti-Aggregation Property of Allicin by In Vitro and Molecular Docking Studies

2019 ◽  
Vol 13 ◽  
pp. 117906951986618 ◽  
Author(s):  
Suresh Kumar ◽  
Shivani Kumar ◽  
Heera Ram
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Molecular Interaction ◽  
Fibril Formation ◽  
Amyloid Peptide ◽  
Peptide Aggregation ◽  
Aβ Peptide ◽  
In Silico Studies

Amyloidogenesis is the process in which amyloid beta (Aβ) peptide aggregation results in plaque formation in central nervous system (CNS) are associated with many neurological diseases such as Alzheimer’s disease. The peptide aggregation initiated from peptide monomers results in formation of dimers, tetramers, fibrils, and protofibrils. The ability of allicin, a lipid-soluble volatile organosulfur biological compound, present in freshly crushed garlic ( Allium sativum L.) to inhibit fibril formation by the Aβ peptide in vitro was investigated in the present study. Inhibition of fibrillogenesis was measured by a Thioflavin T (ThT) fluorescence assay and visualized by transmission electron microscopy (TEM). The molecular interaction between allicin and Aβ peptide was also demonstrated by in silico studies. The results show that allicin strongly inhibited Aβ fibrils by 97% at 300 µM, compared with control (Aβ only) ( P < .001). These results were further validated by visual of fibril formation by transmission microscopy and molecular interaction of amyloid peptide with allicin by molecular docking. Aβ forms favourable hydrophobic interaction with Ile32, Met35, Val36, and Val39, and oxygen of allicin forms hydrogen bond with the amino acid residue Lys28. Allicin anti-amyloidogenic property suggests that this naturally occurring compound may have potential to ameliorate and prevent Alzheimer’s disease.

scholarly journals Design, synthesis, structure, toxicology and in vitro testing of three novel agents for Alzheimer’s disease

RSC Advances ◽  
2017 ◽  
Vol 7 (38) ◽  
pp. 23457-23467 ◽  
Author(s):  
José Daniel Figueroa-Villar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Novel Agents ◽  
In Vitro Testing ◽  
Design Synthesis

This article describes the synthesis of three novel compounds for the treatment of Alzheimer’s disease (AD).

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