Recent advances in the design and discovery of synthetic tyrosinase inhibitors

Li, Jin; Feng, Lu; Liu, Li; Wang, Fang; Ouyang, Liang; Zhang, Lan; Hu, Xiuying; Wang, Guan

doi:10.1016/j.ejmech.2021.113744

Cited by 73 publications

(75 citation statements)

References 187 publications

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“…Noteworthy the antibacterial activity of tyrosinase inhibitors were also confirmed in recent studies. [12] Lots of efforts have been made to discover new chemical pharmacophores that inhibit tyrosinase enzyme to reduce mentioned undesirable impacts with fewer side effects including polyphenol and flavonoids, [13] phenylpropanoids, [14] thioamides, and thioureas, [15] azine, [16] hydrazine, [17] thiosemicarbazide [18] piperazine, [19] benzothiazole, [20] salicylaldehyde bearing bis(sulfonate) [21] as well as quinazolines and quinazolinone [9,22] based derivatives.…”

Section: Introductionmentioning

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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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: Introductionmentioning

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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“…There is great interest in the control of tyrosinase activity, especially through the use of inhibitors, which can be natural or synthetic [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. This enzyme has two activities: firstly, monophenolase activity, catalysing the passage from L-tyrosine to L-dopa, and secondly, diphenolase activity, which catalyses the passage from L-dopa to L- o -dopaquinone [ 1 , 2 ].…”

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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“…Tyrosinase is widespread in microorganisms, plants, animals, and humans, and plays the key role as the rate-limiting enzyme in melanin biosynthesis. 1 Melanin contributes to cuticular hardening and exoskeletal pigmentation in animals, and enzymatic browning in fruits and vegetables. 2 3 And the color of human skin is predominantly determined by the amount of melanin produced by skin melanocytes.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Tyrosinase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation

Wang

Pan

et al. 2022

Pharmaceutical Fronts

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Tyrosinase (EC 1.14.18.1) plays an indispensable role in the rate-limiting steps of melanin biosynthesis, and its uncontrolled activity may result in various diseases, such as albinism, melanoma, freckles, etc. The inhibition of tyrosinase activity may provide a useful and efficient strategy to treat hyperpigmentation disorders. However, the widely used tyrosinase inhibitors, like α-arbutin, hydroquinone, and kojic acid, have many shortcomings, such as lower efficacy and much more side effects. Herein, we reported the use of homology modeling and multistep structure-based virtual screening for the discovery of novel tyrosinase inhibitors. In this study, 10 initial potential hits (compounds T1–T10) were evaluated for enzyme inhibition and kinetic study, with kojic acid being used as a control. Among them, the IC50 values of both T1 (11.56 ± 0.98 μmol/L) and T5 (18.36 ± 0.82 μmol/L) were superior to that of kojic acid (23.12 ± 1.26 μmol/L). Moreover, T1 and T5 were also identified as the effective noncompetitive tyrosinase inhibitors by the subsequent kinetic study. Above all, T1 and T5 may represent the promising drug candidates for hyperpigmentation therapy in pharmaceutical fields, as well as the effective whitening agents in cosmetic applications.

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Recent advances in the design and discovery of synthetic tyrosinase inhibitors

Cited by 73 publications

References 187 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

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

Discovery of Tyrosinase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation

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