2,4-Dihydroxycinnamic Esters as Skin Depigmenting Agents

Kim, Kyung Dong; Song, Min Ho; Yum, Eul Kgun; Jeon, Ok Seon; Ju, Young Woon; Chang, Moon Sik

doi:10.5012/bkcs.2009.30.7.1619

Cited by 8 publications

(1 citation statement)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compound (Ph6) bears an unsubstituted cinnamic acid moiety while compound (Ph7), (Ph8) and (Ph9) possess 2-hydroxy, 4-hydroxy and 2,4-dihydroxy-substituted cinnamic acid component, respectively. The tyrosinase inhibitory activity of 2,4-dihydroxy cinnamic acid is already reported [58] and its incorporation as an ester/amide in compound Ph9 resulted in an increased inhibitory potential. The replacement of hydrogen from the para position of the cinnamic acid phenyl ring in Ph6 with a 2,4-dihydroxyls in Ph9 led to a significant increase in tyrosinase inhibitory activity (Table 1).…”

Section: Structure-activity Relationship (Sar)mentioning

confidence: 84%

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

Section: Structure-activity Relationship (Sar)mentioning

confidence: 84%

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

et al. 2021

View full text Add to dashboard Cite

show abstract

ChemInform Abstract: 2,4‐Dihydroxycinnamic Esters as Skin Depigmenting Agents.

et al. 2009

View full text Add to dashboard Cite

show abstract

Tyrosinase Inhibition and Antimelanogenic Effects of Resorcinol‐Containing Compounds

Beaumet,

Lazinski,

Maresca

et al. 2024

ChemMedChem

View full text Add to dashboard Cite

Tyrosinases (TYRs) are copper‐containing metalloenzymes present in a large diversity of species. In human, hTYR is responsible for pivotal steps in melanogenesis, catalysing the oxidation of l‐tyrosine to l‐DOPA and further to dopaquinone. While numerous TYR inhibitors have been reported, polyphenolic compounds tend to dominate the literature. However, many of these compounds, particularly monophenols and catechols, have been identified as alternative substrates rather than true inhibitors, given their structural similarity to natural substrates. Resorcinol‐containing compounds have emerged as promising candidates to address this challenge, as the meta‐dihydroxy moiety in resorcinol demonstrates resistance to TYR‐mediated oxidation, while retaining the favourable interactions with copper ions provided by the hydroxy groups. Although their precise mechanism of action remains debated, resorcinol derivatives have yielded some of the most active compounds against isolated mushroom and human TYRs, as well as clinically used dermocosmetic agents like rucinol and thiamidol, which exhibited very promising effects in patients with facial melasma. This review outlines the development of resorcinol‐containing TYR inhibitors, categorized by scaffold type, ranging from simple alkyl analogues to intricate synthetic derivatives. Mechanistic insights about the resorcinol–TYR interaction are also presented and debated.

show abstract

2,4-Dihydroxycinnamic Esters as Skin Depigmenting Agents

Cited by 8 publications

References 20 publications

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

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

ChemInform Abstract: 2,4‐Dihydroxycinnamic Esters as Skin Depigmenting Agents.

Tyrosinase Inhibition and Antimelanogenic Effects of Resorcinol‐Containing Compounds

Contact Info

Product

Resources

About