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

Abstract：

:To aid the pharmaceutical and cosmetic industry in the development of alternatives to prevent melanin-related hyperpigmentation disorders, the plant Dalea elegans was submitted to fractionation with the aim of obtaining its anti-tyrosinase principle. Bioguided fractionation of D. elegans led to the isolation of 5,2',4'-trihydroxy-2″,2″-dimethylchromene-(6,7:5″,6″)-flavanone (1) as the active compound. This novel flavanone, named as dalenin, showed notable activity at inhibiting tyrosinase using l-tyrosine or l-DOPA as substrates with IC(50) values of 0.26 and 18.61 μM, respectively. This meant that the flavanone was 52 and 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 the enzyme than hydroquinone and showed the same level of effectiveness as that of kojic acid. It was found that the flavanone behaved as a reversible inhibitor of the enzyme and that it was a mixed-I type or a non-competitive inhibitor with l-tyrosine or l-DOPA as substrates, respectively. Molecular modeling studies were conducted confirming the inhibitory potency of dalenin and showing that the 2',4'-dihydroxy substituents are important for the interaction with the enzyme. The results suggest that compound 1 has great potential to be further developed as a pharmaceutical and cosmetic agent for use in dermatological disorders associated with melanin.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Chiari ME,Vera DM,Palacios SM,Carpinella MC

doi

10.1016/j.bmc.2011.04.025

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

3474-82

issue

11

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(11)00293-8

journal_volume

19

pub_type

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