INVESTIGADORES
CARPINELLA Maria Cecilia
artículos
Título:
Tyrosinase inhibitory activity of a 6-isoprenoid-substituted flavanone isolated from Dalea elegans
Autor/es:
MARÍA EUGENIA CHIARI ; DOMINGO MARIANO A. VERA; SARA MARÍA PALACIOS ; CARPINELLA M.C.
Revista:
BIOORGANIC & MEDICINAL CHEMISTRY.
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Año: 2011 vol. 19 p. 3474 - 3482
ISSN:
0968-0896
Resumen:
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.