Fundamental Investigation on Halogenated Derivatives as Antityrosinase Agent and Inhibition of Enzyme Kinetic Studies
Fatin Farhana Baharuddin (1*), Nadiah Mad Nasir (1), Koh Soo Peng (2), Bimo Ario Tejo (1)

(1): Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, UPM, 43400, Serdang, Malaysia
*ftnfrhzny[at]gmail.com
(2): Pusat Penyelidikan Sains dan Teknologi Makanan, MARDI, 43000, Serdang, Selangor, Malaysia

Abstract

Tyrosinase enzyme catalyses L-tyrosine substrate through oxidation, forming L DOPA and converting to melanins whereby excess melanin promotes hyperpigmentation, ageing and other skin-related diseases. Thus, inducing tyrosinase inhibitors can lower melanin production to achieve whitening properties in the skin. Nowadays, some whitening products such as contain hydroquinone and heavy metals are harmful to human skin. This research aimed to produce 19 nontoxic halogenated tyrosinase inhibitors synthetically using Grover-Shah and Shah (GSS) method and their tyrosinase inhibitory activity using tyrosinase mushroom Agaricus bisporus assay with kojic acid as a positive control. Five compounds were found to inhibit the enzyme with inhibition percentage of more than 50%. Among these active compounds, two compounds (11 and 12) showed potency. Their half maximal inhibitory concentration (IC50) and their enzyme kinetic analysis were determined. The IC50 values for compounds 11 (75 ug/ml) and 12 (100 ug/ml) in L-DOPA substrate demonstrate its strong action with kojic acid as control (7.8 ug/ml). Enzyme kinetic analysis demonstrated that compounds 11 and 12 as uncompetitive inhibitors whereby this kinetic data were supported by visualized docking analysis with tyrosinase protein. These data suggest that halogenated derivatives have the potential to be developed as new candidates for skin whitening agents in cosmetic industries and for pigmentation related diseases.

Keywords: antityrosinase, docking, enzyme, inhibitors, synthesis

Topic: Chemistry