Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
ACS Omega
2023 Nov 21;846:44265-44275. doi: 10.1021/acsomega.3c06977.
Show Gene links
Show Anatomy links
Investigation of Structure-Activity Relationships for Benzoyl and Cinnamoyl Piperazine/Piperidine Amides as Tyrosinase Inhibitors.
Varela MT
,
de Castro Levatti EV
,
Tempone AG
,
Fernandes JPS
.
???displayArticle.abstract???
Melanin is a substance that plays important roles in several organisms. Its function as an antioxidant and metal-complexing agent makes tyrosinase, the key enzyme that controls melanogenesis, an interesting target for designing inhibitors. In this article, we report a set of piperazine/piperidine amides of benzoic and cinnamic acid derivatives as tyrosinase inhibitors with improved potency and drug-likeness. The most potent compound 5b showed a pIC50 of 4.99 in the monophenolase assay, and only compound 3a showed reasonable potency in the diphenolase assay (pIC50, 4.18). These activities are not correlated to antiradical activity, suggesting that the activity is dependent on competition with the substrates. Molecular docking studies indicated that the benzyl substituent of 5b and other analogues perform important interactions in the enzyme that may explain the higher potency of these compounds. Moreover, the compounds present adequate lipophilicity and skin permeability and no relevant cytotoxicity (CC50 > 200 μM) to mammalian cells.
Aranha,
Multitargeting approaches to cognitive impairment: Synthesis of aryl-alkylpiperazines and assessment at cholinesterases, histamine H3 and dopamine D3 receptors.
2023, Pubmed,
Echinobase
Aranha,
Multitargeting approaches to cognitive impairment: Synthesis of aryl-alkylpiperazines and assessment at cholinesterases, histamine H3 and dopamine D3 receptors.
2023,
Pubmed
,
Echinobase
Brown,
Dermal and transdermal drug delivery systems: current and future prospects.
2006,
Pubmed
Chen,
Structure-antioxidant activity relationship of methoxy, phenolic hydroxyl, and carboxylic acid groups of phenolic acids.
2020,
Pubmed
Cordero,
Melanin.
2020,
Pubmed
Daina,
SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules.
2017,
Pubmed
Di,
Drug-like property concepts in pharmaceutical design.
2009,
Pubmed
Fan,
Spectrophotometric Assays for Sensing Tyrosinase Activity and Their Applications.
2021,
Pubmed
Garcia-Jimenez,
Action of tyrosinase on alpha and beta-arbutin: A kinetic study.
2017,
Pubmed
Kedare,
Genesis and development of DPPH method of antioxidant assay.
2011,
Pubmed
Khan,
Tyrosinase inhibitory effect of benzoic acid derivatives and their structure-activity relationships.
2010,
Pubmed
Kipouros,
Elucidation of the tyrosinase/O2/monophenol ternary intermediate that dictates the monooxygenation mechanism in melanin biosynthesis.
2022,
Pubmed
Lai,
Structure and Function of Human Tyrosinase and Tyrosinase-Related Proteins.
2018,
Pubmed
Lambert,
The physiology of melanin deposition in health and disease.
2019,
Pubmed
Land,
YASARA: A Tool to Obtain Structural Guidance in Biocatalytic Investigations.
2018,
Pubmed
Lee,
Using tyrosinase as a monophenol monooxygenase: A combined strategy for effective inhibition of melanin formation.
2016,
Pubmed
Menon,
Benzoic acid inhibition of the alpha, beta, and gamma isozymes of Agaricus bisporus tyrosinase.
1990,
Pubmed
Mirabile,
Evaluation of 4-(4-Fluorobenzyl)piperazin-1-yl]-Based Compounds as Competitive Tyrosinase Inhibitors Endowed with Antimelanogenic Effects.
2021,
Pubmed
Nazir,
Hydroxyl substituted benzoic acid/cinnamic acid derivatives: Tyrosinase inhibitory kinetics, anti-melanogenic activity and molecular docking studies.
2020,
Pubmed
Olivares,
New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins.
2009,
Pubmed
Oliveira,
Coumaric acid analogues inhibit growth and melanin biosynthesis in Cryptococcus neoformans and potentialize amphotericin B antifungal activity.
2020,
Pubmed
Parvez,
Naturally occurring tyrosinase inhibitors: mechanism and applications in skin health, cosmetics and agriculture industries.
2007,
Pubmed
Penney,
Depigmenting action of hydroquinone depends on disruption of fundamental cell processes.
1984,
Pubmed
Pillaiyar,
Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors.
2017,
Pubmed
Ramsden,
Tyrosinase: the four oxidation states of the active site and their relevance to enzymatic activation, oxidation and inactivation.
2014,
Pubmed
Rescigno,
Tyrosinase inhibition: general and applied aspects.
2002,
Pubmed
Romagnoli,
Cinnamic acid derivatives linked to arylpiperazines as novel potent inhibitors of tyrosinase activity and melanin synthesis.
2022,
Pubmed
Satooka,
Effects of thymol on mushroom tyrosinase-catalyzed melanin formation.
2011,
Pubmed
Seo,
Mushroom tyrosinase: recent prospects.
2003,
Pubmed
Singh,
Kojic Acid Peptide: A New Compound with Anti-Tyrosinase Potential.
2016,
Pubmed
Song,
Comparison of the antimelanogenic effects of p-coumaric acid and its methyl ester and their skin permeabilities.
2011,
Pubmed
Souto,
Physicochemical and biopharmaceutical aspects influencing skin permeation and role of SLN and NLC for skin drug delivery.
2022,
Pubmed
Tung,
Antioxidant activities of natural phenolic compounds from Acacia confusa bark.
2007,
Pubmed
Varela,
Coumaric acid derivatives as tyrosinase inhibitors: Efficacy studies through in silico, in vitro and ex vivo approaches.
2020,
Pubmed
Zhang,
Skin solubility determines maximum transepidermal flux for similar size molecules.
2009,
Pubmed
Zhang,
Linear free energy relationship analysis of retention factors in cerasome electrokinetic chromatography intended for predicting drug skin permeation.
2011,
Pubmed
Zolghadri,
A comprehensive review on tyrosinase inhibitors.
2019,
Pubmed
Zou,
Determination of the Bridging Ligand in the Active Site of Tyrosinase.
2017,
Pubmed
