Design, Synthesis, DFT, Molecular Docking, and Biological Evalution of Pyrazole Derivatives as Potent Acetyl Cholinestrease Inhibitors

Abdelwahab, Huda E.; Ibrahim, Hayam M.; Omar, Alaa Z.

doi:10.1016/j.molstruc.2022.134137

Cited by 16 publications

(4 citation statements)

References 39 publications

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“…The TAC of synthetized compounds was evaluated using Rafael Torres-Martínez et al protocol [60]. A total of 100 µL of varying concentrations (14,28,56,113,226, and 452 µM) of the compounds in dimethylsulfoxide (DMSO) was combined with 900 µL of TAC reagent solution (0.6 M sulfuric acid, 28 mM sodium phosphate, and 4 mM ammonium molybdate). For the blank, 100 µL of distilled water was used in place of the compound.…”

Section: Tac By Phosphomolybdenum Methodsmentioning

confidence: 99%

“…Finding potent heterocyclic molecules containing nitrogen with efficient biological activities is a current strategy. An example of this strategy is the biological applications of pyrazole derivatives as potent acetylcholinesterase inhibitors [28]. Another example is the use of pyrano [2,3-c]pyrazole and pyrazolo [4 ,3 :5,6]pyrano [2,3-d]pyrimidine derivatives for their antimicrobial, antioxidant, and anticancer activities [29].…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants

Adardour,

Ait Lahcen,

Oubahmane

et al. 2023

Pharmaceuticals

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In the present study, we used benzimidazolone as a starting material to efficiently synthesize several hybrid compounds of pyrazole benzimidazolone derivatives by the 1,3-dipolar cycloaddition reaction. These compounds were obtained in average yields and were characterized by NMR (1H and 13C) and HRMS analysis. The antioxidant activity of the synthesized compounds 5(a–c) and 6(a–c) was evaluated using in vitro reduction assays, including ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC). The results indicated that products 5c, 6b, and 6c exhibit higher antioxidant activity compared to the reference compounds and showed a remarkable ability to effectively remove the radical at IC50 (14.00 ± 0.14, 12.47± 0.02, and 12.82 ± 0.10 µM, respectively) under the TAC assessment. Conversely, compound 6c showed excellent activity at IC50 (68.97 ± 0.26 µM) in the FRAP assay. We carried out molecular docking and dynamics simulations to investigate the binding mode and stability of 5c, 6b, and 6c in the active site of human Peroxiredoxin 5. An ADMET study was conducted to determine the drug properties of the synthesized compounds.

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Section: Tac By Phosphomolybdenum Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants

Adardour,

Ait Lahcen,

Oubahmane

et al. 2023

Pharmaceuticals

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“…Unlike the concurrent administration of two medications, molecular hybridization offers pharmacokinetic benefits over single ligands. [4][5][6] The molecular hybrids comprising the pyrazole-furan backbone have exhibited diverse pharmacological properties such as antibacterial, [7][8][9] anti-Alzheimer,, [10,11] anticancer, [12][13][14][15] antiinflammatory (Cox-1 and Cox-2), [16] and anti-Parkinson's disease (α-synuclein aggregation inhibitor), [17] (Figure 1). Hence, proves to be a useful scaffold in drug design and discovery.…”

Section: Introductionmentioning

confidence: 99%

Novel Furan‐Pyrazole Molecular Hybrids as Prospective Anti‐Neuroinflammatory Agents: Design, Synthesis, and In‐Vitro Screening Thereof

Mudimela,

Janardhanan

2023

Asian J Org Chem

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Neuro‐inflammatory responses lead to various neurodegenerative disorders. A small library of 1H‐pyrazole‐1‐carbothioamidoacetamido)‐furan‐3‐carboxamide molecular hybrids were designed and subjected to molecular docking against two neuroinflammatory targets, HMGB1 (2LY4) and Box A (4QR9) proteins. The in‐silico investigations indicated notable binding of 9 c and 9 d against HMGB1(2LY4), while compounds 9 c, 9 h, and 9 g demonstrated high affinity towards HMGB1 Box A (4QR9) proteins. A total of ten compounds, which showed good binding interactions with the target proteins were selected for further synthesis and evaluated for anti‐neuroinflammatory activity. The compounds, 9 a–j were synthesized by reacting pyrazole‐carbothioamides (iii & iv) with furanyl acetamides (7a–e). FTIR, NMR, and mass spectrometric data confirmed all structures. The in‐vitro cytotoxicity was evaluated on microglial cells BV‐2, N‐9, HMO6, leukemic HAP1 and human fibroblast cells. Notable suppression of anti‐inflammatory markers TNF‐α, IL‐1β, IL‐6, and Bcl‐2 was observed by 9 a–d and 9 f. All derivatives were moderate in potency compared to reference doxorubicin and could act as novel anti‐neuroinflammatory agents. The current discoveries could provide insights for developing novel lead compounds that could target neuroinflammation and related diseases.

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“…1,2 In some cases, bioisosteric replacement within the imidazole scaffold leading to benzo [d]imidazoles resulted in improved properties as compared with the corresponding parent compound. 3 The imidazole and benzimidazole nuclei are commonly encountered in drugs that display diverse pharmacological activities such as anti-inflammatory, 4 histamine-H3 antagonist, 5 antiviral, 6 antioxidant, 7 gastroprotective, 8 antibacterial, [9][10][11][12][13] antitumoral, 14 and antiparasitic action. The biological relevance of these heteroaromatic groups arises because they are good bioisosters of biomolecules.…”

Section: Introductionmentioning

confidence: 99%

Cyclization of 2,4‐dinitronaphth‐1‐yl amino acids and their analogues to naphthimindazol‐N‐oxides: Kinetics and mechanism

Omar,

Khattab,

Ibrahim

et al. 2023

J of Physical Organic Chem

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A variety of novel naphthimindazol‐N‐oxides and naphththiazol‐N‐oxide have been prepared in a simple two‐step process. The first step involves the reaction of 1‐chloro‐2,4‐dinitronaphthalene with glycine, alanine, glycolic acid, thioglycolic acid, and their methyl esters affording substitution products, the subsequent treatment of which with base furnishes naphthimindazol‐N‐oxide and naphththiazol‐N‐oxide derivatives. Stepwise reaction mechanisms via carbanions, nitrogen anions, and spiro Meisenheimer intermediates are proposed. The action of 10% NaOH in dioxane on the substitution products was measured spectrophotochemically, and the kinetic studies suggested that the N‐naphthyl glycine and N‐naphthyl alanine follow a second‐order rate law while S‐naphthyl thioglycolic acid is accurately first‐order kinetics.

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Design, Synthesis, DFT, Molecular Docking, and Biological Evalution of Pyrazole Derivatives as Potent Acetyl Cholinestrease Inhibitors

Cited by 16 publications

References 39 publications

Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants

Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants

Novel Furan‐Pyrazole Molecular Hybrids as Prospective Anti‐Neuroinflammatory Agents: Design, Synthesis, and In‐Vitro Screening Thereof

Cyclization of 2,4‐dinitronaphth‐1‐yl amino acids and their analogues to naphthimindazol‐N‐oxides: Kinetics and mechanism

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