Anticholinesterase and Antioxidant Activities of Natural Abietane Diterpenoids with Molecular Docking Studies

2020 ◽  
Vol 17 (3) ◽  
pp. 269-284 ◽  
Author(s):  
Gülaçtı Topçu ◽  
Atilla Akdemir ◽  
Ufuk Kolak ◽  
Mehmet Öztürk ◽  
Mehmet Boğa ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Antioxidant Activities ◽  
Cholinergic Neurons ◽  
Docking Studies ◽  
Mammalian Brain ◽  
Abietane Diterpenoids ◽  
Selective Ligand ◽  
Molecular Modelling Studies ◽  
Modelling Studies

Background: Alzheimer’s Disease (AD) is one of the most prevalent causes of dementia in the world, and no drugs available that can provide a complete cure. Cholinergic neurons of the cerebral cortex of AD patients are lost due to increased activity of cholinesterase enzymes. Objectives: Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) are the two major classes of cholinesterases in the mammalian brain. The involvement of oxidative stress in the progression of AD is known. Thus, the objective of this study is to determine strong ChE inhibitors with anti-oxidant activity. Methods: In this study, 41 abietane diterpenoids have been assayed for antioxidant and anticholinesterase (both for AChE and BuChE) properties in vitro, which were previously isolated from Salvia species, and structurally determined by spectroscopic methods, particularly intensive 1D- and 2DNMR and mass experiments. Molecular modeling studies were performed to rationalize the in vitro ChE inhibitory activity of several abietane diterpenoids compared with galantamine. Results: Thirteen out of the tested 41 abietane diterpenoids exhibited at least 50% inhibition on either AChE or BuChE. The strongest inhibitory activity was obtained for Bractealine against BuChE (3.43 μM) and AChE (33.21 μM) while the most selective ligand was found to be Hypargenin E against BuChE enzyme (6.93 μM). A full correlation was not found between anticholinesterase and antioxidant activities. The results obtained from molecular modelling studies of Hypargenin E and Bractealine on AChE and BuChE were found to be in accordance with the in vitro anti-cholinesterase activity tests. Conclusion: Abietane diterpenoids are promising molecules for the treatment of mild-moderate AD.

Efficient synthesis and characterization of novel indolizines: exploration of in vitro COX-2 inhibitory activity and molecular modelling studies

2018 ◽  
Vol 42 (7) ◽  
pp. 4893-4901 ◽  
Author(s):  
Sandeep Chandrashekharappa ◽  
Katharigatta N. Venugopala ◽  
Christophe Tratrat ◽  
Fawzi M. Mahomoodally ◽  
Bandar E. Aldhubiab ◽  
...  
Keyword(s):  
Molecular Modelling ◽  
Inhibitory Activity ◽  
Synthesis And Characterization ◽  
Efficient Synthesis ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Cox 2

Novel indolizine scaffolds as COX-2 inhibiting agents.

Synthesis and Biological Evaluation of 5-benzyl-3-pyridyl-1H-1,2,4-triazole Derivatives as Xanthine Oxidase Inhibitors

2020 ◽  
Vol 16 (1) ◽  
pp. 119-127
Author(s):  
Song-Ye Li ◽  
Ting-Jian Zhang ◽  
Qing-Xia Wu ◽  
Kamara M. Olounfeh ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Binding Pocket ◽  
Biological Evaluation ◽  
Triazole Derivatives ◽  
Xanthine Oxidase Inhibitors ◽  
Ic50 Value ◽  
Molecular Modelling Studies ◽  
Modelling Studies

Background: Topiroxostat is an excellent xanthine oxidase (XO) inhibitor, possessing a specific 3,5-diaryl-1,2,4-triazole framework. Objective: The present work was aimed to investigate the preliminary structure-activity relationship (SAR) of 2-cyanopyridine-4-yl-like fragments of topiroxostat analogues. Methods: A series of 5-benzyl-3-pyridyl-1H-1,2,4-triazole derivatives (1a-j and 2a-j) were designed and synthesized by replacement of the 2-cyanopyridine-4-yl moiety with substituted benzyl groups. XO inhibitory activity in vitro was evaluated. Furthermore, molecular modeling simulations were performed to predict the possible interactions between the synthesized compounds and XO binding pocket. Results: The SARs analysis demonstrated that 3,5-diaryl-1,2,4-triazole framework is not essential; in spite of its lower potency, 5-benzyl-3-pyridyl-1H-1,2,4-triazole is an acceptable scaffold for XO inhibitory activity to some extent. A 3′-nitro and a 4′-sec-butoxy group link to the benzyl moiety will be welcome. Furthermore, the most promising compound, 1h, was identified with an IC50 value of 0.16 μM, and the basis of XO inhibition by 1h was rationalized through the aid of molecular modelling studies. Conclusion: Compound 1h could be a lead compound for further investigation and the present work may provide some insight into the search for more structurally diverse XO inhibitors with topiroxostat as a prototype.

scholarly journals Design, Synthesis and Pharmacological Evaluation of Novel Imidazopyridine Analogues as Proton Pump Antagonist

2020 ◽  
Vol 32 (4) ◽  
pp. 776-782
Author(s):  
Ravindra S. Sonawane ◽  
Kiran D. Patil ◽  
Avinash V. Patil
Keyword(s):  
Spectral Analysis ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Inhibitory Activity ◽  
Positive Control ◽  
Docking Studies ◽  
Design Synthesis ◽  
Standard Drug ◽  
Imidazopyridine Derivatives

A series of novel imidazopyridine derivatives as proton pump inhibitors was designed with compounds of CID data base and explored considering AZD0865 as standard. Many compounds were identified and docked in proton pump ATPase pocket (PDB ID: 4ux2). Molecular docking studies revealed that many compounds showed good proton pump ATPase inhibitory activity. The docking poses revealed the interaction of ligands with amino acid. The standard drug AZD0865 had docking score of -7.112302 and displayed interactions with Asn138 and Asp137. A series of novel imidazopyridine derivatives as proton pump inhibitors were docked, synthesized and characterized by IR, NMR, CHN and MS spectral analysis. The target imidazopyridines were prepared from substituted 2-aminonicotinic acid and 2-bromo-1-substituted ethanone. in vitro Studies explained that few compounds exhibited moderate to good proton pump ATPase inhibitory activity in comparison with the reference drugs i.e. AZD0865. Compounds 11 and 12 shown higher activities with the IC50 4.3. Compounds 1, 4, 6, 7, 8, 10 and 13 showed weak anti-ulcer activity with its IC50 5.2, 5.8, 5.5, 5.1, 4.9, 4.6 and 5.9 and positive control AZD0865 shown IC50 2.0.

Chalcones and bis-chalcones: As potential α-amylase inhibitors; synthesis, in vitro screening, and molecular modelling studies

2018 ◽  
Vol 79 ◽  
pp. 179-189 ◽  
Author(s):  
Adebayo Tajudeen Bale ◽  
Khalid Mohammed Khan ◽  
Uzma Salar ◽  
Sridevi Chigurupati ◽  
Tolulope Fasina ◽  
...  
Keyword(s):  
Molecular Modelling ◽  
In Vitro Screening ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Amylase Inhibitors

scholarly journals Synthesis, Urease Inhibition, Antioxidant, Antibacterial, and Molecular Docking Studies of 1,3,4-Oxadiazole Derivatives

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Muhammad Hanif ◽  
Khurram Shoaib ◽  
Muhammad Saleem ◽  
Nasim Hasan Rama ◽  
Sumera Zaib ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Potassium Hydroxide ◽  
Antioxidant Activities ◽  
Docking Studies ◽  
Potassium Salts ◽  
Jack Bean ◽  
Molecular Docking Studies ◽  
Oxadiazole Derivatives ◽  
Urease Inhibitory

A series of eighteen 1,3,4-oxadiazole derivatives have been synthesized by treating aromatic acid hydrazides with carbon disulfide in ethanolic potassium hydroxide yielding potassium salts of 1,3,4-oxadiazoles. Upon neutralization with 1 N hydrochloric acid yielded crude crystals of 1,3,4-oxadiazoles, which were purified by recrystallization in boiling methanol. The synthesized 1,3,4-oxadiazoles derivatives were evaluated in vitro for their urease inhibitory activities, most of the investigated compounds were potent inhibitors of Jack bean urease. The molecular docking studies were performed by docking them into the crystal structure of Jack bean urease to observe the mode of interaction of synthesized compounds. The synthesized compounds were also tested for antibacterial and antioxidant activities and some derivatives exhibited very promising results.

Synthesis, in vitro antiplatelet activity and molecular modelling studies of 10-substituted 2-(1-piperazinyl)pyrimido[1,2- a ]benzimidazol-4(10 H )-ones

2013 ◽  
Vol 62 ◽  
pp. 564-578 ◽  
Author(s):  
Mario Di Braccio ◽  
Giancarlo Grossi ◽  
Maria Grazia Signorello ◽  
Giuliana Leoncini ◽  
Elena Cichero ◽  
...  
Keyword(s):  
Molecular Modelling ◽  
Antiplatelet Activity ◽  
Molecular Modelling Studies ◽  
Modelling Studies
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