Synthesis, kinetic mechanism and docking studies of vanillin derivatives as inhibitors of mushroom tyrosinase

Ashraf, Zaman; Rafiq, Muhammad; Seo, Sung‐Yum; Babar, Mustafeez Mujtaba; Zaidi, Najam‐us‐Sahar Sadaf

doi:10.1016/j.bmc.2015.06.068

Cited by 86 publications

(40 citation statements)

References 39 publications

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“…The mushroom tyrosinase (EC 1.14.18.1) (Sigma Chemical Co.) was used for in vitro bioevaluation as described previously with some modifications [40–41]. Briefly, 140μL of phosphate buffer (20mM, pH 6.8), 20μL of mushroom tyrosinase (30U/mL) and 20μL of the inhibitor solution were placed in the wells of a 96-well micro plate.…”

Section: Methodsmentioning

confidence: 99%

Carvacrol derivatives as mushroom tyrosinase inhibitors; synthesis, kinetics mechanism and molecular docking studies

et al. 2017

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The present work describesthe development of highly potent mushroom tyrosinase inhibitor better than the standard kojic acid. Carvacrol derivatives 4a-f and 6a-d having substituted benzoic acid and cinnamic acidresidues were synthesized with the aim to possess potent tyrosinase inhibitory activity.The structures of the synthesized compounds were ascertained by their spectroscopic data (FTIR, 1HNMR, 13CNMR and Mass Spectroscopy).Mushroom tyrosinase inhibitory activity of synthesized compounds was determined and it was found that one of the derivative 6c possess higher activity (IC50 0.0167μM) than standard kojic acid (IC50 16.69μM). The derivatives 4c and 6b also showed good tyrosinase inhibitory activity with (IC50 16.69μM) and (IC50 16.69μM) respectively.Lineweaver—Burk and Dixon plots were used for the determination of kinetic mechanism of the compounds 4c and 6b and 6c. The kinetic analysis revealed that compounds 4c and 6b showed mixed-type inhibition while 6c is a non-competitive inhibitor having Ki values19 μM, 10 μM, and 0.05 μMrespectively. The enzyme inhibitory kinetics further showed thatcompounds 6b and 6c formed irreversible enzyme inhibitor complex while 4c bind reversibly with mushroom tyrosinase.The docking studies showed that compound 6c have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-7.90 kcal/mol) as compared to others.The 2-hydroxy group in compound 6c interacts with amino acid HIS85 which is present in active binding site. The wet lab results are in good agreement with the dry lab findings.Based upon our investigation we may propose that the compound 6c is promising candidate for the development of safe cosmetic agent.

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Section: Methodsmentioning

confidence: 99%

Carvacrol derivatives as mushroom tyrosinase inhibitors; synthesis, kinetics mechanism and molecular docking studies

et al. 2017

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“…Free radical scavenging activity of amide derivatives was determined based on previously reported methods with few modifications 28,29. The assay solution consisted of 100 µL of DPPH (150 µM) and 20 µL of increasing concentration of test compounds, and the volume was adjusted to 200 µL in each well with DMSO.…”

Section: Methodsmentioning

confidence: 99%

Development of highly potent melanogenesis inhibitor by in vitro, in vivo and computational studies

Abbas

Ashraf

Hassan

et al. 2017

DDDT

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The present work describes the synthesis of few hydroxylated amide derivatives as melanogenesis inhibitors. In vitro, in vivo and computational studies proved that compound 6d is a highly potent melanogenesis inhibitor compared to standard kojic acid. The title amides 4a–e and 6a–e were synthesized following simple reaction routes with excellent yields. Most of the synthesized compounds exhibited good mushroom tyrosinase inhibitory activity, but compound 6d showed excellent activity (IC50 0.15 µM) compared to standard kojic acid (IC50 16.69 µM). Lineweaver–Burk plots were used for the determination of kinetic mechanism, and it was found that compounds 4c and 6d showed non-competitive inhibition while 6a and 6b showed mixed-type inhibition. The kinetic mechanism further revealed that compound 6d formed irreversible complex with the target enzyme tyrosinase. The Ki values determined for compounds 4c, 6a, 6b and 6d are 0.188, 0.84, 2.20 and 0.217 µM respectively. Results of human tyrosinase inhibitory activity in A375 human melanoma cells showed that compound 6d exhibited 91.9% inhibi-tory activity at a concentration of 50 µg/mL. In vivo cytotoxicity evaluation of compound 6d in zebrafish embryos showed that it is non-toxic to zebrafish. Melanin depigmentation assay performed in zebrafish indicated that compound 6d possessed greater potential in decreasing melanin contents compared to kojic acid at the same concentration. Computational studies also supported the wet lab findings as compound 6d showed a highest binding affinity with the target protein (PDBID: 2Y9X) with a binding energy value of −7.90 kcal/mol. Molecular dynamic simulation studies also proved that amide 6d formed the most stable complex with tyrosinase. Based upon our in vitro, in vivo and computational studies, we propose that compound 6d is a promising candidate for the development of safe cosmetic agent.

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“…Tyrosinase is also responsible for the production of neuromelanin. Excessive production of dopaquinone by oxidation of dopamine results in neuronal damage and cell death [37]. For this reason, this enzyme contributed to the neurodegeneration associated with Parkinson's disease and other neurodegenerative disease processes [38].…”

Section: Introductionmentioning

confidence: 99%

“…Also, cancers are characterized by abnormalities in tyrosinase activity [39]. Tyrosinase is also associated with the host defense, wound healing, melting, and sclerotization of insects [40]. Tyrosinase inhibitors were widely used in food, agriculture, and cosmetic industries and in the control of molting process of insects.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of S-Substituted Perhalo-2-nitrobuta-1,3-dienes as Novel Xanthine Oxidase, Tyrosinase, Elastase, and Neuraminidase Inhibitors

Onul

Ertik

Mermer

et al. 2018

Journal of Chemistry

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S-substituted perhalo-2-nitrobuta-1,3-dienes 3a, b were synthesized by the reaction of polyhalo-2-nitrobuta-1,3-dienes 1a, b with allyl mercaptan. 1-(2,3-Dibromopropanethio)-4-bromo-1,3,4-trichloro-2-nitrobuta-1,3-diene 4 was obtained from the addition of bromine to S-substituted polyhalo-2-nitrobuta-1,3-diene 3b in carbon tetrachloride. Sulfoxides 5a, b, and 6 were obtained from the reaction of thiosubstituted polyhalonitrobutadienes 3a, b, and 4 with m-CPBA in CHCl 3 . The structures of the new compounds were determined by spectroscopic data (FTIR, 1 H NMR, 13 C NMR, MS). These compounds exhibited antixanthine oxidase, antityrosinase, antielastase, and antineuraminidase activities.

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Synthesis, kinetic mechanism and docking studies of vanillin derivatives as inhibitors of mushroom tyrosinase

Cited by 86 publications

References 39 publications

Carvacrol derivatives as mushroom tyrosinase inhibitors; synthesis, kinetics mechanism and molecular docking studies

Carvacrol derivatives as mushroom tyrosinase inhibitors; synthesis, kinetics mechanism and molecular docking studies

Development of highly potent melanogenesis inhibitor by in vitro, in vivo and computational studies

Synthesis and Biological Evaluation of S-Substituted Perhalo-2-nitrobuta-1,3-dienes as Novel Xanthine Oxidase, Tyrosinase, Elastase, and Neuraminidase Inhibitors

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