MYCOLab Ai Logo - gold and army green

Molecular Docking, Synthesis, and Tyrosinase Inhibition Activity of Acetophenone Amide: Potential Inhibitor of Melanogenesis

Summary

Researchers developed new chemical compounds that can inhibit tyrosinase, an enzyme responsible for producing melanin (the pigment that colors skin). One compound, called 5c, proved exceptionally effective at blocking this enzyme—significantly more potent than existing skin-lightening agents. These acetophenone-based compounds could lead to improved cosmetic treatments for unwanted pigmentation like age spots and melasma, with better safety profiles than current options.

Background

Tyrosinase is a binuclear copper-containing metalloenzyme responsible for melanin biosynthesis and pigmentation disorders. Abnormal melanin accumulation causes dermatological disorders including melasma, freckle, and lentigo. Tyrosinase inhibition is an established strategy for treating hyperpigmentation and developing new cosmetic agents.

Objective

To synthesize and evaluate acetophenone amide derivatives incorporating hydroxyl-substituted benzoic and cinnamic acid moieties as potential tyrosinase inhibitors. To explore the structure-activity relationship and determine binding mechanisms through in vitro and computational studies.

Results

Compound 5c exhibited superior tyrosinase inhibition with IC₅₀ of 0.0020 ± 0.0002 μM, significantly more potent than kojic acid (16.69 ± 2.8 μM) and arbutin (191.17 ± 5.5 μM). Kinetic analysis revealed 5c acts as a competitive, reversible inhibitor with Ki value of 0.0072 μM. Docking studies showed hydrogen bonding with Asn 260 and Asn 81 residues in the active site.

Conclusion

Hydroxyl-substituted cinnamic acid derivatives, particularly 5c, demonstrate potent tyrosinase inhibitory activity suitable for cosmetic formulations and antimelanogenic applications. The acetophenone amide scaffold represents a valuable scaffold for designing novel melanogenesis inhibitors with improved efficacy over existing agents.
  • Published in:Biomed Res Int,
  • Study Type:Experimental Research - Synthesis and Enzymatic Analysis,
  • Source: PMID: 35059457, DOI: 10.1155/2022/1040693
Scroll to Top