Tyrosinase inhibitory activity of a 6-isoprenoid-substituted flavanone isolated from Dalea elegans

M. E. CHIARI; D. M. A. VERA; S. M. PALACIOS; M. C. CARPINELLA

Bioorganic & Medicinal Chemistry

ELSEVIER

Año: 2011 vol. 19 p. 3474 - 3482

0968-0896

To aid the pharmaceutical and cosmetic industry in the development of alternatives to prevent melaninrelatedhyperpigmentation disorders, the plant Dalea elegans was submitted to fractionation with the aimof obtaining its anti-tyrosinase principle. Bioguided fractionation of D. elegans led to the isolation of5,20,40-trihydroxy-200,200-dimethylchromene-(6,7:500,600)-flavanone (1) as the active compound. This novelflavanone, named as dalenin, showed notable activity at inhibiting tyrosinase using L-tyrosine or L-DOPAas substrates with IC50 values of 0.26 and 18.61 lM, respectively. This meant that the flavanone was 52and 495 times more effective as a monophenolase inhibitor than hydroquinone and kojic acid, respectively.With L-DOPA as a substrate, compound 1 showed itself 59 times more effective at inhibiting theenzyme than hydroquinone and showed the same level of effectiveness as that of kojic acid. It was foundthat the flavanone behaved as a reversible inhibitor of the enzyme and that it was a mixed-I type or anon-competitive inhibitor with L-tyrosine or L-DOPA as substrates, respectively. Molecular modelingstudies were conducted confirming the inhibitory potency of dalenin and showing that the 20,40-dihydroxysubstituents are important for the interaction with the enzyme.The results suggest that compound 1 has great potential to be further developed as a pharmaceuticaland cosmetic agent for use in dermatological disorders associated with melanin. 2011 Elsevier Ltd. All rights reserved.