Synthesis and molecular modeling of new 2‐benzylidenethiobarbituric acid derivatives as potent tyrosinase inhibitors agents

Najafi, Zahra; Kamari‐aliabadi, Adel; Sabourian, Reyhaneh; Hajimahmoodi, Mannan; Chehardoli, Gholamabbas

doi:10.1002/jccs.202100537

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…In addition, missing atoms were corrected and atomic Gasteiger charges were calculated and added. The scoring grid box for tyrosinase was reported previously [86]; its parameters are X-center: −8.064, Y-center: −25.776, Z-center: −39.384; grid size: 60 × 60 × 60 points, and the spacing value: 0.375 Å. The grid maps for energy scoring were calculated using AutoGrid.…”

Section: Molecular Docking Studymentioning

confidence: 99%

Screening of the Anti-Neurodegenerative Activity of Caffeic Acid after Introduction into Inorganic Metal Delivery Systems to Increase Its Solubility as the Result of a Mechanosynthetic Approach

Stasiłowicz-Krzemień

Rosiak

Miklaszewski

et al. 2023

IJMS

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The proven anti-neurodegenerative properties of caffeic acid in vivo are limited due to its poor solubility, which limits bioavailability. Therefore, caffeic acid delivery systems have been developed to improve caffeic acid solubility. Solid dispersions of caffeic acid and magnesium aluminometasilicate (Neusilin US2—Neu) were prepared using the ball milling and freeze-drying techniques. The solid dispersions of caffeic acid:Neu obtained by ball milling in a 1:1 mass ratio turned out to be the most effective. The identity of the studied system in comparison to the physical mixture was confirmed using the X-Ray Powder Diffractionand Fourier-transform infrared spectroscopy techniques. For caffeic acid with improved solubility, screening tests were carried out to assess its anti-neurodegenerative effect. The obtained results on the inhibition of acetylcholinesterase, butyrylcholinesterase, tyrosinase, and antioxidant potential provide evidence for improvement of caffeic acid’s anti-neurodegenerative activity. As a result of in silico studies, we estimated which caffeic acid domains were involved in interactions with enzymes showing expression relevant to the neuroprotective activity. Importantly, the confirmed improvement in permeability of the soluble version of caffeic acid through membranes simulating the walls of the gastrointestinal tract and blood-brain barrier further strengthen the credibility of the results of in vivo anti-neurodegenerative screening tests.

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Section: Molecular Docking Studymentioning

confidence: 99%

Screening of the Anti-Neurodegenerative Activity of Caffeic Acid after Introduction into Inorganic Metal Delivery Systems to Increase Its Solubility as the Result of a Mechanosynthetic Approach

Stasiłowicz-Krzemień

Rosiak

Miklaszewski

et al. 2023

IJMS

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“…Data analysis was done with Microsoft Excel 2016 software. Also, all rate measurements were performed three times [31] …”

Section: Methodsmentioning

confidence: 99%

“…Pharmacokinetic properties and ADME prediction were done according to our previously reported papers. [29,31]…”

Section: Prediction Of Pharmacokinetic Propertiesmentioning

confidence: 99%

Fused 1,4‐Dihydropyridines and Their Corresponding Pyridines: Synthesis, Molecular Modeling and Cholinesterase Inhibition

et al. 2023

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Novel series of fused 1,4‐dihydropyridine derivatives were designed and synthesized. Oxidized to the corresponding pyridines were these dihydropyridines. Both dihydropyridines and pyridines were evaluated as acetyl and butyrylcholinesterase inhibitors. 1,4‐dihydropyridine derivatives outperformed pyridines against the butyrylcholinesterase enzyme, but none had a suitable inhibitory effect against acetylcholinesterase. Among the 1,4‐dihydropyridines, compounds derived from vanillin (4 j–p) inhibited butyrylcholinesterase (BChE) with IC50 values of 2.87–15.61 μM, but compounds derived from 4‐hydroxybenzaldehyde did not show a suitable inhibitory effect against butyrylcholinesterase. Among them, the compound 9‐(4‐((4‐Chlorobenzyl)oxy)‐3‐methoxyphenyl)‐3,4,6,7,9,10‐hexahydroacridine‐1,8(2H,5H)‐dione (4 p) showed appropriate inhibitory activity against BChE with an IC50 value of 2.87 μM compared with tacrine and donepezil as reference drugs (0.005 and 0.95 μM, respectively). The most outstanding results of kinetic and molecular modeling studies is that compound 4 p acts as a mixed and dual binding inhibitor, and binds to CAS and PAS of the BChE enzyme. These results show that with minor changes in the structure of fused 1,4‐dihydropyridines, new anti‐Alzheimer drugs with better performance can be achieved.

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“…After the reaction was completed, ice was added to the mixture and stirred for 10 minutes. Then, the derivatives 4 a – f were filtered and washed with cold water to purify [14] …”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, and Molecular Dynamics Simulation Studies of New Chalcone‐Based 2‐Arylidene‐1,3‐indandiones as Tyrosinase Inhibitors

Najafi,

Rafiei,

Ghafouri‐Khosrowshahi

et al. 2023

ChemistrySelect

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In this work, we synthesized a series of chalcone‐based 2‐arylidene‐1,3‐indandione and evaluated their inhibitory activities against the mushroom tyrosinase enzyme. Based on benzylidene moiety, derivatives were divided into 4‐benzyloxy‐benzylidene and 4‐benzyloxy‐3‐methoxy‐benzylidene derivatives. Among them, 2‐(3‐methoxy‐4‐((4‐methylbenzyl)oxy)benzylidene)‐1H‐indene‐1,3(2H)‐dione (6 l) was presented the superior activity with an IC50 value of 15.85±3.64 μM, which was lower than the standard kojic acid. The kinetic study of compound 6 l displayed an uncompetitive inhibition mode on the tyrosinase enzyme. Next, the docking study exhibited compound 6 l formed hydrogen bonds and hydrophobic interactions with critical highly conserved amino acids in the target protein. Furthermore, based on the molecular dynamics simulation, compound 6 l depicted noticeable interaction with the essential residues of the binding site and exhibited a stable complex during the simulation run. The methoxy group on the central ring was important in inducing the effective conformation for ligand‐enzyme interaction. The drug‐likeness and pharmacokinetic properties were calculated via in silico predictions and showed an acceptable profile for these agents. According to our results, it was proposed that compound 6 l can serve as a drug candidate to develop more potent antityrosinase agents.

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Synthesis and molecular modeling of new 2‐benzylidenethiobarbituric acid derivatives as potent tyrosinase inhibitors agents

Cited by 8 publications

References 21 publications

Screening of the Anti-Neurodegenerative Activity of Caffeic Acid after Introduction into Inorganic Metal Delivery Systems to Increase Its Solubility as the Result of a Mechanosynthetic Approach

Screening of the Anti-Neurodegenerative Activity of Caffeic Acid after Introduction into Inorganic Metal Delivery Systems to Increase Its Solubility as the Result of a Mechanosynthetic Approach

Fused 1,4‐Dihydropyridines and Their Corresponding Pyridines: Synthesis, Molecular Modeling and Cholinesterase Inhibition

Design, Synthesis, and Molecular Dynamics Simulation Studies of New Chalcone‐Based 2‐Arylidene‐1,3‐indandiones as Tyrosinase Inhibitors

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