FLAVONOIDS ISOLATED FROM DALEA ELEGANS INHIBIT MELANOGENESIS IN MOUSEB16

MELANOMA CELLS

MARÍA DANIELA SANTI,MARIANA PERALTA, JOSÉ LUIS CABRERA, MARÍA GABRIELA ORTEGA

Facultadde Ciencias Químicas,Universidad Nacional de Córdoba,IMBIV-CONICET,Argentina

Tyrosinaseinhibitor compounds have importance in the

treatmentof hyperpigmentation diseases and are used

aswhiteners agents in cosmetics. Several currently marketed

whitenershave adverse effects; for example Kojic

acid(KA) is genotoxic, hepatocarcinogenic and produces

dermatitis.For this reason is important the researching for

newinhibitors of tyrosinase. Previously we have reported

animportant inhibitory activity on mushroom tyrosinase

by a prenylated flavanone (8PP) and achalcone (Triangularin)

isolatedfrom roots and aerial parts of Dalea

elegansGillies ex Hook. & Arn. In order to investigate

thiscondition in cell line, we evaluate the melanogenesis

inhibitionof these compounds on mouse B16 melanoma

cellsthrough the tyrosinase intracelular inhibition and the

extracelularmelanin inhibition by spectrophotometrically

measuringof the adduct formation between 3-methyl-

2-benzothiazolinoneand dopaquinona. The cytotoxicity

assay was performedby MTT methodology. The maximum

non-cytotoxicconcentration (MNCC) for 8PP, Triangularin

andKA were of 10 μM, 100 μM and 5000 μM, respectively

andaccording with these results we evaluated the

melanogenesisinhibition. The results demonstrated that

thesecompounds have the ability to penetrate the membrane

ofB16 cells and inhibit the tyrosinase intracelular

atnon-cytotoxic concentrations. Comparing the inhibition

%of each compound with reference inhibitor KA,

8PPand Triangularin would be two hundred-fold and

Five-fold more active than KA, respectively.In addition,

ithas been observed that these compounds decreased

extracellularmelanin. The 50 % of inhibition for 8PP and

Triangularinwere 1 and 25 μM, respectively. For KA, the

50% of inhibition was 2000 μM. So, 8PP and Triangularin

wouldbe two thousand and eighty-fold more active than

KA,respectively. It would be needed PCR and Western

blotstudies to establish the mechanisms by which these

compounds act onmelanin biosynthesis.