New chalcone derivative, ethyl 2-(4-(3-(benzo[b]thiophen-2-yl)acryloyl)phenoxy)acetate: synthesis, characterization, DFT study, enzyme inhibition activities and docking study

Putative Molecular Mechanisms of Neuroprotective Cerebrosides and Their Docking Studies on Acetyl Cholinesterase Enzyme Inhibition for the Treatment of Alzheimer’s Disease

10.21203/rs.3.rs-756424/v1 ◽

2021 ◽

Author(s):

SHAIK IBRAHIM KHALIVULLA ◽

Kokkanti Mallikarjuna

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Enzyme Inhibition ◽

Docking Study ◽

Tau Proteins ◽

World Health ◽

Molecular Docking Study ◽

Ache Inhibitors ◽

Catalytic Active Site

Abstract The Dementia disease is characterised by neuropsychiatric disturbances due to lack of proper synaptic communication between neurons causing the cognitive behavioural problems. The Alzheimer’s disease (AD) in elderly population is one of the several forms of Dementia. Recent data by World Health Organisation indicates that nearly 10 million people are getting dementia every year, of which 60-70% accounts for AD. The etiology of AD involves the formation of amyloid-β plaques and neurofibrillary Tau tangles in the brain resulting in the death of neural cells. There is no permanent solution for AD treatment, except the FDA approved drugs like galantamine, donepezil, rivastigmine and memantine that are normally associated with side effects. At this juncture, cerebrosides, the natural secondary metabolites identified from different taxa with potential neuroprotective effects offer a promising scope for the treatment of AD. In this paper, cerebrosides reported from all taxa are pooled up along with their functions and listed. The review of literature revealed that Cerebrosides can increase the cognitive functions by regulating or interacting with the N-methyl-d-aspartate (NMDA) calcium ion (Ca2+) channels at post-synaptic receptor; nitric oxide (NO); Bcl2, Bax, amyloid precursor (APP) and Tau proteins; brain-derived neurotrophic factor (BDNF) and cAMP- response element-binding proteins (CREB).This indicates that the Cerebrosides could be potential therapeutic agents for the protection of neurons involved in neurodegenerative disease like Alzheimer’s disease. The current neuroprotective drugs are AChE inhibitors; hence, in the present investigation, in silico molecular docking study on cerebrosides for the inhibition of AChE was assessed to find out their capacity to interact with an active catalytic site of AChE. The results of present investigation revealed that all 22 cerebrosides selected for this work interacted with catalytic active site of AChE measured in terms of Gibbs free binding energy. Of all the cerebrosides assessed, compound 6 exhibited strong interaction, followed by 15. This is the first report of molecular docking study on cerebrosides for AChE enzyme inhibition for treatment of Alzheimer’s disease. Nevertheless, detailed in vitro and in vivo, biochemical and molecular investigations are needed to bring them to useful form.

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An In-silico and In-vitro Comparative Study of Compounds from Phoenix sylvestris Roxb. For Alpha-Amylase Enzyme Inhibition Involved in Diabetes Mellitus

Biointerface Research in Applied Chemistry ◽

10.33263/briac115.1334713358 ◽

2021 ◽

Vol 11 (5) ◽

pp. 13347-13358

Keyword(s):

Ethyl Acetate ◽

Enzyme Inhibition ◽

Ethyl Acetate Extract ◽

Binding Free Energy ◽

Docking Study ◽

Alpha Amylase ◽

Amino Acid Residues ◽

Docking Method ◽

Treatment Of Diabetes

Identification of potential phytocompound from Phoenix sylvestris RoxB. For anti-diabetic potential and its validation through computational methods. Partially purified fraction evaluated for Alpha-amylase enzyme inhibition and GC-MS identified fraction validated compounds for potential anti-diabetic activity by Auto docking method. The phytocompounds investigation revealed maximum abundance of total phenol (31.55±0.55 μg/mg equivalent to Gallic acid) and flavonoid (52.90±0.08 μg/mg equivalent to quercetin) content in ethyl acetate extract. Ethyl acetate extract interestingly showed maximum alpha-amylase inhibition (71.15 %, IC50- 98.50±0.10 μg/ml), which was a mixed type of inhibition as compared to acarbose (78.64%, IC50- 88.61±0.50 μg/ml), which showed a competitive type of inhibition analyzed by Line weaver-Burk double reciprocal plot versus 1/v and 1/s. The docking study illustrated that Lupenyl acetate compound was the most active compound that showed maximum binding free energy (-7.16 Kcal/mol) and interacted with the Val64, Asn88, Gly90, Asn87, Arg87, Arg10, Gly9, Gln7, Gln5, Thr5, Trp221, Phe222, Asn5, Pro223, Ser3, Ser226, Lys227 and Gly225 amino acid residues which inhibited the alpha-amylase more efficiently than acarbose (binding energy -4.71 Kcal/mol). The present study concluded that the components of ethyl acetate extract had Alpha enzyme inhibition with reducing potential, and it may be due to the synergistic effect. The study suggested ethyl acetate extract as a natural promising therapeutic compound for the treatment of diabetes.

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Synthesis, Biological Evaluation (Antioxidant, Antimicrobial, Enzyme Inhibition, and Cytotoxic) and Molecular Docking Study of Hydroxy Methoxy Benzoin/Benzil Analogous

Bioorganic Chemistry ◽

10.1016/j.bioorg.2021.105183 ◽

2021 ◽

pp. 105183

Author(s):

Nurettin Yaylı ◽

Gözde Kılıç ◽

Nuran Kahriman ◽

Şeyda Kanbolat ◽

Arif Bozdeveci ◽

...

Keyword(s):

Molecular Docking ◽

Enzyme Inhibition ◽

Docking Study ◽

Biological Evaluation ◽

Molecular Docking Study

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Tyrosinase Inhibitory Activity, 3D QSAR, and Molecular Docking Study of 2,5-Disubstituted-1,3,4-Oxadiazoles

Journal of Chemistry ◽

10.1155/2013/849782 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Ramesh L. Sawant ◽

Prashant D. Lanke ◽

Jyoti B. Wadekar

Keyword(s):

Enzyme Inhibition ◽

Inhibitory Activity ◽

3D Qsar ◽

Docking Study ◽

Docking Studies ◽

Maximum Activity ◽

Tyrosinase Inhibitor ◽

Molecular Docking Study ◽

Tyrosinase Inhibitory Activity ◽

Vlife Mds

In continuation with our research program, in search of potent enzyme tyrosinase inhibitor, a series of synthesized 2,5-disubstituted 1,3,4-oxadiazoles have been evaluated for enzyme tyrosinase inhibitory activity. Subsequently, 3D QSAR and docking studies were performed to find optimum structural requirements for potent enzyme tyrosinase inhibitor from this series. The synthesized 20 compounds of 2,5-disubstituted-1,3,4-oxadiazole series were screened for mushroom tyrosinase inhibitory activity at various concentrations by enzyme inhibition assay. The percentage enzyme inhibition was calculated by recording absorbance at 492 nm with microplate reader. 3D QSAR and docking studies were performed using VLife MDS 3.5 software. In the series 2,5-disubstituted-1,3,4-oxadiazoles enzyme tyrosinase inhibitory activity was found to be dose dependent with maximum activity for compounds4c,4h,4m, and4r. 3D QSAR and docking studies revealed that more electropositive and less bulky substituents if placed on 1,3,4-oxadiazole nucleus may result in better tyrosinase inhibitory activity in the series.

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