Synthesis and biological assessment of novel 4H-chromene-3-carbonitrile derivatives as tyrosinase inhibitors
- Author: mycolabadmin
- 9/28/2024
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Summary
Researchers developed new chemical compounds that can block tyrosinase, an enzyme responsible for producing excessive skin pigment that causes dark spots and discoloration. The most effective compound (6f) works better than kojic acid, a commonly used skin-lightening ingredient, and could lead to safer treatments for hyperpigmentation and related skin conditions. Computer simulations showed that one form of the compound fits better into the enzyme’s active site, making it more effective at preventing melanin production.
Background
Excessive tyrosinase activity during melanogenesis results in hyperpigmentation and various skin disorders. While kojic acid is an FDA-approved tyrosinase inhibitor, its clinical use is limited by skin irritation and chemical instability. Novel chromene-based analogs have shown promise as potential tyrosinase inhibitors.
Objective
To synthesize a novel series of 4H-chromene-3-carbonitrile derivatives and evaluate their inhibitory activities against tyrosinase enzyme. The study aimed to identify potent inhibitors and elucidate their mechanism of action through kinetic studies, molecular docking, and molecular dynamics simulations.
Results
Compound 6f exhibited the most potent tyrosinase inhibition with IC50 of 35.38 ± 2.12 µM and showed competitive inhibition with Ki = 16.15 µM. Molecular docking revealed π-π stacking and hydrogen bonding interactions with His263, Val283, and Phe264. Molecular dynamics simulations demonstrated that the R-enantiomer of 6f exhibited superior binding stability and persistent interactions compared to the S-enantiomer.
Conclusion
- Published in:BMC Chemistry,
- Study Type:In vitro experimental study with computational analysis,
- Source: 10.1186/s13065-024-01305-0, PMID: 39342248