In vitro and in silico insights into tyrosinase inhibitors with (E)-benzylidene-1-indanone derivatives

Jung, Hyun Ah; Noh, Sang Gyun; Park, Yujin; Kang, Dong-Wan; Chun, Pusoon; Chung, Hae Young; Moon, Hyung Ryong

doi:10.1016/j.csbj.2019.07.017

Cited by 32 publications

(23 citation statements)

References 66 publications

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“…[1] Tyrosinase (EC 1.14.18.1) is a copper containing enzyme that catalyzes the rate-limiting step of melanin biosynthesis: the conversion of tyrosine in l-DOPA and its oxidation in o-dopaquinone. [6,7] Its active site contains a binuclear copper center with six histidine residues involved in the coordination of the two metal ions. [8] The inhibition of tyrosinase activity is a widely used strategy for blocking melanogenesis thus reducing melanin synthesis.…”

Section: Introductionmentioning

confidence: 99%

4‐Fluorobenzylpiperazine‐Containing Derivatives as Efficient Inhibitors of Mushroom Tyrosinase

et al. 2020

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Tyrosinase is a type‐3 copper protein involved in the biosynthesis of melanin pigments; therefore, the inhibition of its enzymatic activity represents a promising strategy for the treatment of hyperpigmentation‐related disorders. To address this point, we previously designed a class of 4‐(4‐fluorobenzyl)piperazin‐1‐yl‐based compounds, which proved to be more active inhibitors against tyrosinase from mushroom Agaricus bisporus than the positive control kojic acid. Herein, we report the synthesis of further series of 4‐(4‐fluorobenzyl)piperazin‐1‐yl analogues bearing a (hetero)aromatic fragment as key feature to improve protein affinity. The newly synthesized compounds were assayed in vitro and proved to be potent inhibitors in the low‐micromolar range. The active 2‐thienyl and 2‐furyl derivatives were selected for further modification to allow their binding mode to be analyzed by docking studies and to give satisfactory safety profiles.

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Section: Introductionmentioning

confidence: 99%

4‐Fluorobenzylpiperazine‐Containing Derivatives as Efficient Inhibitors of Mushroom Tyrosinase

et al. 2020

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“…Mushroom tyrosinase inhibition was determined following our previously reported methods [ 37 ]. All experiments were done in triplicate.…”

Section: Methodsmentioning

confidence: 99%

(E)-1-(Furan-2-yl)-(substituted phenyl)prop-2-en-1-one Derivatives as Tyrosinase Inhibitors and Melanogenesis Inhibition: An In Vitro and In Silico Study

et al. 2020

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A series of (E)-1-(furan-2-yl)prop-2-en-1-one derivatives (compounds 1–8) were synthesized and evaluated for their mushroom tyrosinase inhibitory activity. Among these series, compound 8 (2,4-dihydroxy group bearing benzylidene) showed potent tyrosinase inhibitory activity, with respective IC50 values of 0.0433 µM and 0.28 µM for the monophenolase and diphenolase as substrates in comparison to kojic acid as standard compound 19.97 µM and 33.47 µM. Moreover, the enzyme kinetics of compound 8 were determined to be of the mixed inhibition type and inhibition constant (Ki) values of 0.012 µM and 0.165 µM using the Lineweaver-Burk plot. Molecular docking results indicated that compound 8 can bind to the catalytic and allosteric sites 1 and 2 of tyrosinase to inhibit enzyme activity. The computational molecular dynamics analysis further revealed that compound 8 interacted with two residues in the tyrosinase active site pocket, such as ASN260 and MET280. In addition, compound 8 attenuated melanin synthesis and cellular tyrosinase activity, simulated by α-melanocyte-stimulating hormone and 1-methyl-3-isobutylxanthine. Compound 8 also decreased tyrosinase expressions in B16F10 cells. Based on in vitro and computational studies, we propose that compound 8 might be a worthy candidate for the development of an antipigmentation agent.

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“…For instance, phthalic acid formed hydrogen bonds with W136, W141 and G149 and van der Waals interactions with D137, W138, G139, Y140, F147 and F224 whereas cinnamic acid form hydrogen bonds with Q307 and D312 and van der Waals interactions with T308, Y311, V313, Y314, E356 and W358. Jung et al [46] also reported a mixed-type tyrosinase inhibitor, (E)-2-(2,4-dihydroxybenzylidene)-2,3-dihydro-1H-inden-1-one (BID3) which formed a hydrogen bond with Y140 and interacted hydrophobically with L24, F147 and I148. These findings suggest potential peptide interaction with non-specific binding site of the enzyme since the allosteric site of mushroom tyrosinase has yet to be identified.…”

Section: Identification Of Bioactive Peptidesmentioning

confidence: 99%

Chicken Egg White—Advancing from Food to Skin Health Therapy: Optimization of Hydrolysis Condition and Identification of Tyrosinase Inhibitor Peptides

Yap

Gan

2020

Foods

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Active fragments (bioactive peptides) from the chicken egg white proteins were expected to exert tyrosinase inhibitory activities in which skin hyperpigmentation could be prevented. Egg white was hydrolyzed by trypsin, chymotrypsin and the combination of both enzymes. The enzyme treatments achieved >50% degree of hydrolysis (DH) at substrate-to-enzyme (S/E) ratio of 10–30 (w/w) and hydrolysis time of 2–5 h. A crossed D-optimal experimental design was then used to determine the optimal enzyme composition, S/E ratio and hydrolysis time in order to yield hydrolysates with strong monophenolase and diphenolase inhibitory activities. The optimized conditions 55% trypsin, 45% chymotrypsin, S/E 10:1 w/w and 2 h achieved 45.9% monophenolase activity inhibition whereas 100% trypsin, S/E 22.13:1 w/w and 3.18 h achieved 48.1% diphenolase activity inhibition. LC/MS and MS/MS analyses identified the peptide sequences and the subsequent screening had identified 7 peptides (ILELPFASGDLLML, GYSLGNWVCAAK, YFGYTGALRCLV, HIATNAVLFFGR, FMMFESQNKDLLFK, SGALHCLK and YFGYTGALR) as the potential inhibitor peptides. These peptides were able to bind to H85, H94, H259, H263, and H296 (hotspots for active residues) as well as F92, M280 and F292 (stabilizing residues) of tyrosinase based on structure-activity relationship analysis. These findings demonstrated the potential of egg white-derived bioactive peptides as skin health therapy.

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In vitro and in silico insights into tyrosinase inhibitors with (E)-benzylidene-1-indanone derivatives

Cited by 32 publications

References 66 publications

4‐Fluorobenzylpiperazine‐Containing Derivatives as Efficient Inhibitors of Mushroom Tyrosinase

4‐Fluorobenzylpiperazine‐Containing Derivatives as Efficient Inhibitors of Mushroom Tyrosinase

(E)-1-(Furan-2-yl)-(substituted phenyl)prop-2-en-1-one Derivatives as Tyrosinase Inhibitors and Melanogenesis Inhibition: An In Vitro and In Silico Study

Chicken Egg White—Advancing from Food to Skin Health Therapy: Optimization of Hydrolysis Condition and Identification of Tyrosinase Inhibitor Peptides

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