Phthalimide-1,2,3-triazole hybrid compounds as tyrosinase inhibitors; synthesis, biological evaluation and molecular docking analysis

Tehrani, Maliheh Barazandeh; Emani, Parisa; Rezaei, Zahra; Khoshneviszadeh, Mahsima; Ebrahimi, Mohaddeseh; Edraki, Najmeh; Mahdavi, Mohammad; Larijani, Bagher; Ranjbar, Sara; Foroumadi, Alireza; Khoshneviszadeh, Mehdi

doi:10.1016/j.molstruc.2018.08.033

Cited by 43 publications

(20 citation statements)

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“…The oxygen atoms of the NO 2 group on the phenyl ring interacted via two strong hydrogen bonds with side chain N-Hs of Arg268 and phthalimide moiety involved in a p-H interaction with Val283. 86 Peruzzotti et al developed N-[2methyl-5(triazol-1-yl)phenyl]pyrimidin-2-amine derivatives through in situ click chemistry, which inhibit tyrosine kinase. This compound 48 displayed good inhibition activity against Abl kinase (IC 50 ¼ 0.9 AE 0.1 mM).…”

Section: Introductionmentioning

confidence: 99%

CuAAC-ensembled 1,2,3-triazole-linked isosteres as pharmacophores in drug discovery: review

et al. 2020

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Section: Introductionmentioning

confidence: 99%

CuAAC-ensembled 1,2,3-triazole-linked isosteres as pharmacophores in drug discovery: review

et al. 2020

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“…Thus, we used in silico approaches to predict the pharmacokinetics and the toxicological potential of 101 phthalimide-1,2,3-triazole derivatives, aiming to identify leader compounds against SARS-CoV-2 ( Figure 1 ). These compounds were categorized according to the radicals attached to the 1,2,3-triazole-phthalimide nucleus into groups A-H, as showed in supplementary material ( Tables S1–S8 ): ( A ) derivatives containing benzyl substituents (Tehrani et al, 2019 ); ( B ) derivatives containing phenyl or benzothiazole groups (Da Silva et al, 2019); ( C ) derivatives containing carbohydrate groups and an additional phthalimide (Assis et al, 2012 ); ( D ) compounds with N -phenylacetamides substituents (Phatak et al, 2019 ); ( E ) presence of benzimidazole group between phtalimide-triazole nucleus and three radicals variations (Singh et al, 2020 ); ( F ) thalidomide derivative analogues (Ronnebaum & Luzzio, 2016 ); ( G ) derivatives of phthalimide-benzamide-1,2,3-triazole (Sadat-Ebrahimi et al, 2020 ); and ( H ) derivatives with an additional phthalimide (López-González et al, 2016 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of 1,2,3-triazole-phthalimide derivatives as potential drugs against COVID-19: a virtual screening, docking and molecular dynamic study

Holanda

Lima

Silva

et al. 2021

Journal of Biomolecular Structure and Dynamics

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In this work we aimed to perform an in silico predictive screening, docking and molecular dynamic study to identify 1,2,3-triazole-phthalimide derivatives as drug candidates against SARS-CoV-2. The in silico prediction of pharmacokinetic and toxicological properties of hundred one 1,2,3-triazole-phtalimide derivatives, obtained from SciFinderV R library, were investigated. Compounds that did not show good gastrointestinal absorption, violated the Lipinski's rules, proved to be positive for the AMES test, and showed to be hepatotoxic or immunotoxic in our ADMET analysis, were filtered out of our study. The hit compounds were further subjected to molecular docking on SARS-CoV-2 target proteins. The ADMET analysis revealed that 43 derivatives violated the Lipinski's rules and 51 other compounds showed to be positive for the toxicity test. Seven 1,2,3-triazole-phthalimide derivatives (A7, A8, B05, E35, E38, E39, and E40) were selected for molecular docking and MFCC-ab initio analysis. The results of molecular docking pointed the derivative E40 as a promising compound interacting with multiple target proteins of SARS-CoV-2. The complex E40-M pro was found to have minimum binding energy of À10.26 kcal/mol and a general energy balance, calculated by the quantum mechanical analysis, of À8.63 eV. MD simulation and MMGBSA calculations confirmed that the derivatives E38 and E40 have high binding energies of À63.47 ± 3 and À63.31 ± 7 kcal/mol against SARS-CoV-2 main protease. In addition, the derivative E40 exhibited excellent interaction values and inhibitory potential against SAR-Cov-2 main protease and viral nucleocapsid proteins, suggesting this derivative as a potent antiviral for the treatment and/or prophylaxis of COVID-19.

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“…In our previous study, we proved that some phthalimide–1,2,3‐triazole (Figure 1b) hybrid structures were potent tyrosinase inhibitors. [ 32 ] On the basis of these findings, 5‐benzylidene (thio)barbiturate–1,2,3‐triazole hybrids bearing different benzyl moieties were designed (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…[ 25 ] 1,2,3‐Triazole‐containing compounds have shown a broad range of biological activities such as anticancer, [ 26 ] antibacterial, [ 27 ] anti‐inflammatory, [ 28 ] antifungal, [ 29 ] antitubercular, [ 30 ] antiacetylcholinesterase, [ 31 ] and antityrosinase activities. [ 32,33 ]…”

Section: Introductionmentioning

confidence: 99%

1,2,3‐Triazole‐linked 5‐benzylidene (thio)barbiturates as novel tyrosinase inhibitors and free‐radical scavengers

Ranjbar

Shahvaran

Edraki

et al. 2020

Archiv der Pharmazie

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In this study, benzyl-1,2,3-triazole-linked 5-benzylidene (thio)barbiturate derivatives 7a-d and 8a-h were designed as potential tyrosinase inhibitors and free-radical scavengers. The twelve derivatives were synthesized via the [3+2] cycloaddition reaction of the corresponding benzyl azide as a dipole and the corresponding alkyne as a dipolarophile in the presence of copper(I) species, generated in situ from copper (II)/ascorbate. The thiobarbiturate derivative 8h and the barbiturate derivative 8b bearing 4-fluoro and 4-bromo groups on the benzyl-triazole moiety were found to be the most potent tyrosinase inhibitors with IC 50 values of 24.6 ± 0.9 and 26.8 ± 0.8 μM, respectively. Almost all the compounds showed a good radical scavenging activity with EC 50 values in the range of 29.9-324.9 μM. Derivatives 7a, 8f, and 8h were the most potent free-radical scavengers with EC 50 values of 29.9 ± 0.8, 36.8 ± 0.9, and 39.2 ± 1.1 μM, respectively. The kinetic analysis revealed that compound 8h was a mixed-type tyrosinase inhibitor. The molecular docking analysis indicated that 8b and 8h were well accommodated in the active site of the tyrosinase enzyme and possessed the most negative binding energy values of −8.55 and −8.81 kcal/mol, respectively. Moreover, it was found that the two residues, Asn81 and Glu322, played a significant role in forming stable enzyme-inhibitor complexes.

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Phthalimide-1,2,3-triazole hybrid compounds as tyrosinase inhibitors; synthesis, biological evaluation and molecular docking analysis

Cited by 43 publications

References 30 publications

CuAAC-ensembled 1,2,3-triazole-linked isosteres as pharmacophores in drug discovery: review

CuAAC-ensembled 1,2,3-triazole-linked isosteres as pharmacophores in drug discovery: review

Identification of 1,2,3-triazole-phthalimide derivatives as potential drugs against COVID-19: a virtual screening, docking and molecular dynamic study

1,2,3‐Triazole‐linked 5‐benzylidene (thio)barbiturates as novel tyrosinase inhibitors and free‐radical scavengers

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