NDLI: Methoxy-Substituted Tyramine Derivatives Synthesis, Computational Studies and Tyrosinase Inhibitory Kinetics

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Methoxy-Substituted Tyramine Derivatives Synthesis, Computational Studies and Tyrosinase Inhibitory Kinetics

Content Provider	MDPI
Author	Nazir, Yasir Rafique, Hummera Kausar, Naghmana Abbas, Qamar Ashraf, Zaman Rachtanapun, Pornchai Jantanasakulwong, Kittisak Ruksiriwanich, Warintorn
Copyright Year	2021
Description	Targeting tyrosinase for melanogenesis disorders is an established strategy. Hydroxyl-substituted benzoic and cinnamic acid scaffolds were incorporated into new chemotypes that displayed in vitro inhibitory effects against mushroom and human tyrosinase for the purpose of identifying anti-melanogenic ingredients. The most active compound 2-((4-methoxyphenethyl)amino)-2-oxoethyl (E)-3-(2,4-dihydroxyphenyl) acrylate (Ph9), inhibited mushroom tyrosinase with an IC50 of 0.059 nM, while 2-((4-methoxyphenethyl)amino)-2-oxoethyl cinnamate (Ph6) had an IC50 of 2.1 nM compared to the positive control, kojic acid IC50 16700 nM. Results of human tyrosinase inhibitory activity in A375 human melanoma cells showed that compound (Ph9) and Ph6 exhibited 94.6% and 92.2% inhibitory activity respectively while the positive control kojic acid showed 72.9% inhibition. Enzyme kinetics reflected a mixed type of inhibition for inhibitor Ph9 (Ki 0.093 nM) and non-competitive inhibition for Ph6 (Ki 2.3 nM) revealed from Lineweaver–Burk plots. In silico docking studies with mushroom tyrosinase (PDB ID:2Y9X) predicted possible binding modes in the catalytic site for these active compounds. Ph9 displayed no PAINS (pan-assay interference compounds) alerts. Our results showed that compound Ph9 is a potential candidate for further development of tyrosinase inhibitors.
Starting Page	2477
e-ISSN	14203049
DOI	10.3390/molecules26092477
Journal	Molecules
Issue Number	9
Volume Number	26
Language	English
Publisher	MDPI
Publisher Date	2021-04-23
Access Restriction	Open
Subject Keyword	Molecules Medicinal Chemistry Tyramine Derivatives Tyrosinase Inhibitors Inhibitory Activity Enzyme Kinetics Mechanism Computational Studies
Content Type	Text
Resource Type	Article

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