A Series of New Hydrazone Derivatives: Synthesis, Molecular Docking and Anticholinesterase Activity Studies

2020 ◽  
Vol 20 (11) ◽  
pp. 1042-1060
Author(s):  
İrem Bozbey ◽  
Zeynep Özdemir ◽  
Harun Uslu ◽  
Azime Berna Özçelik ◽  
Fatma Sezer Şenol ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Enzyme Inhibitor ◽  
Scoring Function ◽  
Docking Studies ◽  
Anticholinesterase Activity ◽  
Serine Hydrolase ◽  
Docking Approach ◽  
Lamarckian Genetic Algorithm ◽  
Inhibitory Agents ◽  
Ellman’S Method

Background: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known to be serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh), which is a significant neurotransmitter for regulation of cognition in animals. Inhibition of cholinesterases is an effective method to curb Alzheimer’s disease, a progressive and fatal neurological disorder. Objective: In this study, 30 new hydrazone derivatives were synthesized. Then we evaluated their anticholinesterase activity of compounds. We also tried to get insights into binding interactions of the synthesized compounds in the active site of both enzymes by using molecular docking approach. Methods: The compounds were synthesized by the reaction of various substituted/nonsubstituted benzaldehydes with 6-(substitute/nonsubstituephenyl)-3(2H)-pyridazinone-2-yl propiyohydrazide. Anticholinesterase activity of the compounds was determined using Ellman’s method. Molecular docking studies were done by using the ADT package version 1.5.6rc3 and showed by Maestro. RMSD values were obtained using Lamarckian Genetic Algorithm and scoring function of AutoDock 4.2 release 4.2.5.1 software. Results: The activities of the compounds were compared with galantamine as cholinesterase enzyme inhibitor, where some of the compounds showed higher BChE inhibitory activity than galantamine. Compound F111 was shown to be the best BChE inhibitor effective in 50 μM dose, providing 89.43% inhibition of BChE (IC50=4.27±0.36 μM). Conclusion: This study supports that novel hydrazone derivates may be used for the development of new BChE inhibitory agents.

scholarly journals Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor

2021 ◽  
Vol 22 (7) ◽  
pp. 3595
Author(s):  
Md Afjalus Afjalus Siraj ◽  
Md. Sajjadur Rahman ◽  
Ghee T. Tan ◽  
Veronique Seidel
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Binding Affinity ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Cannabinoid Type 1 Receptor ◽  
Docking Approach

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

scholarly journals The structural diversity of ginsenosides affects their cholinesterase inhibitory potential

2020 ◽  
Vol 45 (2) ◽  
Author(s):  
Eda Özturan Özer ◽  
Oya Unsal Tan ◽  
Suna Turkoglu
Keyword(s):  
Molecular Docking ◽  
Enzyme Inhibitor ◽  
Direct Interaction ◽  
Structural Diversity ◽  
Docking Studies ◽  
Catalytic Triad ◽  
Active Components ◽  
Molecular Docking Studies ◽  
Protein Ligand Interactions ◽  
Ligand Interactions

AbstractBackground/ObjectiveGinsenosides, the major active components of the ginseng, are known to have various effects on nervous systems. The present study aimed to clarify the inhibition potentials of ginsenosides Rb1, Rc, Re and Rg1 on acetylcholinesterase (AChE) and butrylcholinesterase (BChE) activities, and to evaluate the underlying mechanisms of inhibitions provided by protein-ligand interactions considering their probable candidates of prodrug.Materials and methodsThe inhibitory mechanisms of ginsenosides related with their structural diversity were analyzed kinetically and protein-ligand interactions for both enzymes were evaluated with most potent ginsenosides, by molecular docking studies.ResultsGinsenosides Re and Rg1, with sugar moieties attached to the C-6 and C-20 positions of core structure were found to possess the most powerful inhibitory effect on AChE and BChE activities. Molecular docking studies have been confirmed by kinetic studies. Ginsenosides having a direct interaction with amino acid residues belonging to the catalytic triad revealed the most powerful inhibition with lowest enzyme-inhibitor dissociation constant (Ki) values.ConclusionsGinsenosides Re and Rg1, either alone or in a specific combination, may provide beneficial effects on neurodegenerative pathologies in therapeutic terms.

scholarly journals Species of the Genus Salix L.: Biochemical Screening and Molecular Docking Approach to Potential Acetylcholinesterase Inhibitors

2019 ◽  
Vol 9 (9) ◽  
pp. 1842 ◽  
Author(s):  
Emilia Gligorić ◽  
Ružica Igić ◽  
Ljiljana Suvajdžić ◽  
Nevena Grujić-Letić
Keyword(s):  
Antioxidant Activity ◽  
Molecular Docking ◽  
Total Phenolics ◽  
Woody Species ◽  
Acetylcholinesterase Inhibitors ◽  
Docking Studies ◽  
Willow Species ◽  
Docking Approach ◽  
Willow Bark ◽  
Inhibitory Potential

The genus Salix includes about 500 different, mainly woody species with potentially significant medicinal values. The aim of this study was to evaluate the chemical composition and antioxidant activity of little-studied bark and leaves extracts of seven different species of the genus Salix, and to examine the acetylcholinesterase (AChE) inhibitory potential of selected compounds. The extracts were characterized by High Pressure Liquid Chromatography (HPLC). Total phenolics and flavonoids content was determined spectrophotometrically and the antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and hydroxyl radical (•OH) scavenging assays. Molecular docking studies were conducted in order to elucidate the interaction and binding affinity between selected compounds of willow bark and leaves against AChE. The major components in bark and leaves of most of the species were rutin (1.26–22.09 mg/g), salicin (1.62–17.33 mg/g), chlorogenic acid (0.74–7.53 mg/g) and epicatechin (0.71–4.83 mg/g). The latter three compounds demonstrated significant inhibitory potential against AChE in docking studies. All extracts exhibited notable antioxidant activity as scavengers of both DPPH• and •OH. The obtained results indicate that willow species other than those in commercial use, and not only bark, but willow leaves as well, could be utilized as sources of valuable phytocompounds with antioxidant and neuroprotective properties.

scholarly journals 1 Molecular Docking and Enzymatic Evaluation to Identify Selective Inhibitors of Aspartate Semialdehyde Dehydrogenase

2018 ◽  
Author(s):  
Amarjit Luniwal
Keyword(s):  
Molecular Docking ◽  
Molecular Modeling ◽  
Enzyme Inhibitors ◽  
Selective Inhibition ◽  
Essential Amino Acids ◽  
Docking Studies ◽  
Selective Inhibitors ◽  
Semialdehyde Dehydrogenase ◽  
Docking Approach ◽  
Molecular Modeling And Docking

Microbes that have gained resistance against antibiotics pose a major emerging threat to human health. New targets must be identified that will guide the development of new classes of antibiotics. The selective inhibition of key microbial enzymes that are responsible for the biosynthesis of essential metabolites can be an effective way to counter this growing threat. Aspartate semialdehyde dehydrogenases (ASADHs) produce an early branch point metabolite in a microbial biosynthetic pathway for essential amino acids and for quorum sensing molecules. In this study, molecular modeling and docking studies were performed to achieve two key objectives that are important for the identification of new selective inhibitors of ASADH. First, virtual screening of a small library of compounds was used to identify new core structures that could serve as potential inhibitors of the ASADHs. Compounds have been identified from diverse chemical classes that are predicted to bind to ASADH with high affinity. Next, molecular docking studies were used to prioritize analogs within each class for synthesis and testing against representative bacterial forms of ASADH from Streptococcus pneumoniae and Vibrio cholerae. These studies have led to new micromolar inhibitors of ASADH, demonstrating the utility of this molecular modeling and docking approach for the identification of new classes of potential enzyme inhibitors.

scholarly journals Herbal Compounds from Syzygium aromaticum and Cassia acutifolia as a Shield against SARS-CoV-2 Mpro: a Molecular Docking Approach

2021 ◽  
Vol 11 (6) ◽  
pp. 14853-14865
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
New Drugs ◽  
In Vivo Studies ◽  
Syzygium Aromaticum ◽  
Amino Acid Residues ◽  
Ligand Interaction ◽  
Docking Approach ◽  
Novel Coronavirus

Novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was first identified in China in December 2019. Currently, the novel coronavirus disease 2019 (COVID-19) is the most infectious disease worldwide. In the absence of a vaccine or drug, herbal compounds may be used to treat or control this disease. To explore novel potent inhibitors that suppress this virus's growth, we performed molecular docking studies on SARS-CoV-2 Mpro using 17 effective herbal compounds, along with three reference drugs. Docking results showed that crategolic acid from Syzygium aromaticum (clove) had the highest binding affinity with SARS-CoV-2 Mpro protease, followed by sennoside (A, B, C, and D) compounds from Cassia acutifolia (Sana Makki). Crategolic acid and sennoside (A, B, C, and D) contain amino acid residues and hydrogen bonds involved in the protein-ligand interaction. The present study confirms that crategolic acid and sennoside represent the strongest potential inhibitors of SARS-CoV-2 Mpro. This study's results may help in vivo studies validate the usefulness of compounds from clove and Sana Makki in preparing herbal medicine for the treatment of COVID-19. This analysis supports the production of new drugs for the treatment and control of COVID-19.

scholarly journals Evaluation of Lens culinaris phytochemicals in binding to the 3C-like protease of SARS-CoV-2 – A molecular docking approach

2020 ◽  
Vol 72 ◽  
pp. 173-176
Author(s):  
Anamul Hasan ◽  
Rownak Jahan ◽  
Khoshnur Jannat ◽  
Tohmina Afroze Bondhon ◽  
Md Shahadat Hossan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Lens Culinaris ◽  
Docking Studies ◽  
Polyphenolic Compounds ◽  
Binding Affinities ◽  
The Novel ◽  
Molecular Docking Studies ◽  
Docking Approach ◽  
Novel Coronavirus ◽  
Scientific Attention

The novel coronavirus known as SARS-CoV-2 and the virus-induced disease COVID-19 has caused widespread concerns due to its contagiousness, fatality rate, and the absence of drug(s). This study investigated Lens culinaris and its phytochemicals, especially the flavonoids. The compounds were assessed through molecular docking studies for their binding abilities with the major protease of the novel coronavirus, SARS-CoV-2 (PDB: 6LU7). A total of 42 phytochemicals of Lens culinaris were analyzed through molecular docking studies for their binding affinities to COVID 3C-like protease. Of them, 23 compounds were found to have binding affinities to the protease of −7.5 kcal/mol or higher. Our study indicates that Lens culinaris contains a number of polyphenolic compounds as well as phytosterols, which can bind to the active site of the protease, and so merits further scientific attention on trials for use as potential anti-COVID-19 drugs.

Molecular Docking Studies of Bioactive Nicotiflorin against 6W63 Novel Coronavirus 2019 (COVID-19)

2020 ◽  
Vol 23 ◽  
Author(s):  
Raghvendra Dubey ◽  
Kushagra Dubey
Keyword(s):  
Molecular Docking ◽  
Data Bank ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Molegro Virtual Docker ◽  
Main Protease ◽  
Docking Approach ◽  
Inhibitory Potential ◽  
Efficacy Parameters ◽  
Novel Coronavirus

Background: COVID-19 which is known as the novel coronavirus was reported in December 2019 in Wuhan city, China and many of the patients have been contaminated by environmental contamination and transmission from one human to another. Objective: The objective of work is to establish the inhibitory potential of nicotiflorin, a Kaempferol 3-O-rutinoside flavonoid, against the deadly coronavirus (COVID-19) 6W63 (main protease 3Clpro protein) , using molecular docking approach. Method: The Molegro Virtual Docker software (MVD) with a 30 Å grid resolution was used. The structure was drawn by Chem 3D software and energy minimization was done by the MM2 force field. The protein 6W63 was downloaded from the protein data bank. Molegro modeller was used for score calculations. Result: The molecular docking studies were carried out on nicotiflorin and standard inhibitor X77, where standard inhibitor was observed in a co-crystallized state with main protease 3Clpro protein 6W63. The MolDock score, Rerank Sore and H Bond score of nicotiflorin and standard inhibitor X77 was observed as -173.058, -127.302, -21.9398 and -156.913,- 121.296,-5.7369, respectively. Conclusion: Molecular docking studies have confirmed that the affinity of flavonoid nicotiflorin with the amino acids of the viral protein 6W63 was relatively more than the standard X77. For the effective treatment of novel coronavirus COVID-19, the effectiveness of the identified flavonoid nicotiflorin can further be evaluated for safety and efficacy parameters at both preclinical and clinical stages.

scholarly journals Synthesis and Evaluation of Central Antinociceptive activity of Ring Substituted Chalcones; Molecular Docking Studies with Monoacylglycerol Lipase (MAGL) Enzyme

2018 ◽  
Vol 34 (4) ◽  
pp. 1890-1897
Author(s):  
Shaheen Begum ◽  
Arifa Begum ◽  
Bharathi Koganti
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Docking Studies ◽  
Antinociceptive Activity ◽  
Monoacylglycerol Lipase ◽  
Serine Hydrolase ◽  
Acceptor Property ◽  
Methoxy Groups ◽  
Tail Immersion ◽  
Michael Acceptors

Chalcones possess Michael acceptor property due to the presence of α,β-unsaturated enone moiety in their structure. In the present study, molecular docking was performed to predict binding affinity of ring substituted chalcones with Monoacylglycerol lipase (MAGL), a serine hydrolase enzyme which can inhibited by Michael acceptors such as maleimide derivatives. 3, 4-Dimethoxy derivative, 3h, with -44.45 kJmol-1 of interaction energy, exhibited highest binding affinity and formed Pi-Sulphur interactions with methionine-123 residue of MAGL enzyme. As MAGL is an emerging target for antinociceptive drug development, ring substituted chalcones were synthesized and evaluated for their central antinociceptive activity using tail immersion and hot plate methods. The results revealed that compound 3h, chalcone bearing methoxy groups at 3rd and 4th positions of phenyl ring exhibited good antinociceptive activity in both the models. Good correlation was observed between antinociceptive activity and binding affinity toward MAGL in case of compound 3h.

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