Design, synthesis, in vitro and in silico studies of novel Schiff base derivatives of 2‐hydroxy‐4‐methoxybenzamide as tyrosinase inhibitors

Iraji, Aida; Panahi, Zahra; Khoshneviszadeh, Mahsima; Khoshneviszadeh, Mehdi

doi:10.1002/ddr.21771

Cited by 19 publications

(15 citation statements)

References 30 publications

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“…Tyrosinase inhibitory activity of synthesized compounds was determined according to our previous study [17,41] . Briefly, 10 μL of 0.5 mg/ml of tyrosinase enzyme (5771 units/mg solid) was mixed with 160 μL of phosphate buffer at pH=6.8 (50 mM) in 96‐well microplate and 10 μL of the test sample (different concentrations prepared in DMSO) was added to each well.…”

Section: Methodsmentioning

confidence: 99%

“…Tyrosinase inhibitory activity of synthesized compounds was determined according to our previous study. [17,41] Briefly, 10 μL of 0.5 mg/ml of tyrosinase enzyme (5771 units/mg solid) was mixed with 160 μL of phosphate buffer at pH = 6.8 (50 mM) in 96-well microplate and 10 μL of the test sample (different concentrations prepared in DMSO) was added to each well. The plate was incubated for 20 min at 28 °C and 20 μL of L-dopa solutions (5 mM) as substrate was added to each well and then the absorbance of the mixtures was measured at 475 nm.…”

Section: Tyrosinase Bioassaymentioning

confidence: 99%

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Rational Design, Synthesis, in Vitro, and in Silico Studies of Chlorophenylquinazolin‐4(3H)‐One Containing Different Aryl Acetohydrazides as Tyrosinase Inhibitors

Hajimiri

Khosravikia

Khoshneviszadeh

et al. 2022

Chemistry & Biodiversity

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Tyrosinase plays a pivotal role in the hyperpigmentation and enzymatic browning of fruit and vegetable. Therefore, tyrosinase inhibitors can be of interest in industries as depigmentation compounds as well as anti‐browning agents. In the present study, a series of chlorophenylquinazolin‐4(3H)‐one derivative were rationally designed and synthesized. The formation of target compounds was confirmed by spectral characterization techniques such as IR, 1H‐NMR, 13C‐NMR, and elemental analysis. Among the synthesized derivatives, compound 8l was proved to be the most potent inhibitor with an IC50 value of 25.48±1.19 μM. Furthermore, the results of the molecular docking study showed that this compound fitted well in the active site of tyrosinase with the binding score of −10.72.

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Section: Methodsmentioning

confidence: 99%

Section: Tyrosinase Bioassaymentioning

confidence: 99%

Rational Design, Synthesis, in Vitro, and in Silico Studies of Chlorophenylquinazolin‐4(3H)‐One Containing Different Aryl Acetohydrazides as Tyrosinase Inhibitors

Hajimiri

Khosravikia

Khoshneviszadeh

et al. 2022

Chemistry & Biodiversity

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“…The validity of the docking procedure was tested using the co-crystallized inhibitor as ligand and the above-mentioned protocol. Finally, conformations having the lowest assumed free energies of binding were studied to be analyzed [ 55 ].…”

Section: Methodsmentioning

confidence: 99%

Design, synthesis, and biological evaluation of symmetrical azine derivatives as novel tyrosinase inhibitors

et al. 2021

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A series of symmetrical azine derivatives containing different substituted benzyl moieties were designed, synthesized, and evaluated for their inhibitory activity against tyrosinase. The results showed that compounds 3e, 3f, 3h, 3i, 3j, and 3k possess effective tyrosinase inhibition with IC50 values ranging from 7.30 μM to 62.60 μM. Particularly, compounds 3f displayed around three-fold improvement in the potency (IC50 = 7.30 ± 1.15 μM) compared to that of kojic acid (IC50 = 20.24 ± 2.28 μM) as the positive control. Kinetic study of compound 3f confirmed uncompetitive inhibitory activity towards tyrosinase indicating that it can bind to enzyme–substrate complex. Next, molecular docking analysis was performed to study the interactions and binding mode of the most potent compound 3f in the tyrosinase active site. Besides, the cytotoxicity of 3f, as well as its potency to reduce the melanin content were also measured on invasive melanoma B16F10 cell line. Also, 3f exhibited above 82% cell viability in the A375 cell line at 10 µM. Consequently, compounds 3f could be introduced as a potent tyrosinase inhibitor that might be a promising candidate in the cosmetics, medicine, and food industry.

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“…Diphenolase activity is of the Michaelian type and is normally used to study the kinetics of inhibitors, characterizing the type of inhibition and the strength of the inhibitor [ 13 ]. In addition, a parameter is calculated, the IC 50 , which indicates the concentration of inhibitor that causes 50% inhibition under certain experimental conditions [ 14 , 15 ]. This IC 50 parameter is related to the value of the apparent inhibition constant,

[ 16 ].…”

Section: Introductionmentioning

confidence: 99%

The Relationship between the IC50 Values and the Apparent Inhibition Constant in the Study of Inhibitors of Tyrosinase Diphenolase Activity Helps Confirm the Mechanism of Inhibition

et al. 2022

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Tyrosinase is the enzyme involved in melanization and is also responsible for the browning of fruits and vegetables. Control of its activity can be carried out using inhibitors, which is interesting in terms of quantitatively understanding the action of these regulators. In the study of the inhibition of the diphenolase activity of tyrosinase, it is intriguing to know the strength and type of inhibition. The strength is indicated by the value of the inhibition constant(s), and the type can be, in a first approximation: competitive, non-competitive, uncompetitive and mixed. In this work, it is proposed to calculate the degree of inhibition (iD), varying the concentration of inhibitor to a fixed concentration of substrate, L-dopa (D). The non-linear regression adjustment of iD with respect to the initial inhibitor concentration [I]0 allows for the calculation of the inhibitor concentration necessary to inhibit the activity by 50%, at a given substrate concentration (IC50), thus avoiding making interpolations between different values of iD. The analytical expression of the IC50, for the different types of inhibition, are related to the apparent inhibition constant (KIapp). Therefore, this parameter can be used: (a) To classify a series of inhibitors of an enzyme by their power. Determining these values at a fixed substrate concentration, the lower IC50, the more potent the inhibitor. (b) Checking an inhibitor for which the type and the inhibition constant have been determined (using the usual methods), must confirm the IC50 value according to the corresponding analytical expression. (c) The type and strength of an inhibitor can be analysed from the study of the variation in iD and IC50 with substrate concentration. The dependence of IC50 on the substrate concentration allows us to distinguish between non-competitive inhibition (iD does not depend on [D]0) and the rest. In the case of competitive inhibition, this dependence of iD on [D]0 leads to an ambiguity between competitive inhibition and type 1 mixed inhibition. This is solved by adjusting the data to the possible equations; in the case of a competitive inhibitor, the calculation of KI1app is carried out from the IC50 expression. The same occurs with uncompetitive inhibition and type 2 mixed inhibition. The representation of iD vs. n, with n=[D]0/KmD, allows us to distinguish between them. A hyperbolic iD vs. n representation that passes through the origin of coordinates is a characteristic of uncompetitive inhibition; the calculation of KI2app is immediate from the IC50 value. In the case of mixed inhibitors, the values of the apparent inhibition constant of meta-tyrosinase (Em) and oxy-tyrosinase (Eox), KI1app and the apparent inhibition constant of metatyrosinase/Dopa complexes (EmD) and oxytyrosinase/Dopa (EoxD), KI2app are obtained from the dependence of iD vs. n, and the results obtained must comply with the IC50 value.

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Design, synthesis, in vitro and in silico studies of novel Schiff base derivatives of 2‐hydroxy‐4‐methoxybenzamide as tyrosinase inhibitors

Cited by 19 publications

References 30 publications

Rational Design, Synthesis, in Vitro, and in Silico Studies of Chlorophenylquinazolin‐4(3H)‐One Containing Different Aryl Acetohydrazides as Tyrosinase Inhibitors

Rational Design, Synthesis, in Vitro, and in Silico Studies of Chlorophenylquinazolin‐4(3H)‐One Containing Different Aryl Acetohydrazides as Tyrosinase Inhibitors

Design, synthesis, and biological evaluation of symmetrical azine derivatives as novel tyrosinase inhibitors

The Relationship between the IC50 Values and the Apparent Inhibition Constant in the Study of Inhibitors of Tyrosinase Diphenolase Activity Helps Confirm the Mechanism of Inhibition

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