Molecules (Basel, Switzerland), 2020-11, Vol.25 (22), p.5460
2020
Details
- Autor(en) / Beteiligte
- Titel
- ( 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
- Ist Teil von
- Molecules (Basel, Switzerland), 2020-11, Vol.25 (22), p.5460
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- A series of ( )-1-(furan-2-yl)prop-2-en-1-one derivatives (compounds - ) were synthesized and evaluated for their mushroom tyrosinase inhibitory activity. Among these series, compound (2,4-dihydroxy group bearing benzylidene) showed potent tyrosinase inhibitory activity, with respective IC 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 were determined to be of the mixed inhibition type and inhibition constant ( ) values of 0.012 µM and 0.165 µM using the Lineweaver-Burk plot. Molecular docking results indicated that compound 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 interacted with two residues in the tyrosinase active site pocket, such as ASN260 and MET280. In addition, compound attenuated melanin synthesis and cellular tyrosinase activity, simulated by α-melanocyte-stimulating hormone and 1-methyl-3-isobutylxanthine. Compound also decreased tyrosinase expressions in B16F10 cells. Based on in vitro and computational studies, we propose that compound might be a worthy candidate for the development of an antipigmentation agent.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1420-3049eISSN: 1420-3049DOI: 10.3390/molecules25225460Titel-ID: cdi_doaj_primary_oai_doaj_org_article_7b82348561f34e1d86cb7aee3168f42f
- Format
- –
- Schlagworte
- Acids, Agaricales - enzymology, Allosteric properties, Animals, Binding Sites, Cell Survival - drug effects, Computer applications, Computer Simulation, Enzymatic activity, Enzyme activity, Enzyme Inhibitors - chemical synthesis, Enzyme Inhibitors - chemistry, Enzyme Inhibitors - pharmacology, Enzyme kinetics, furan-chalcone, Furans - chemical synthesis, Furans - chemistry, Furans - pharmacology, Inhibitory Concentration 50, Kinetics, Kojic acid, Melanin, Melanins - antagonists & inhibitors, Melanocyte-stimulating hormone, melanogenesis, Melanoma, Experimental - pathology, Mice, Molecular docking, Molecular Docking Simulation, Molecular dynamics, Molecular Dynamics Simulation, Monophenol Monooxygenase - antagonists & inhibitors, Monophenol Monooxygenase - metabolism, Mushrooms, Simulation, Skin, Substrates, Tyrosinase, tyrosinase inhibitor