Design, synthesis and evaluation of tyrosinease inhibition effects of kojic acid derivatives with their cytotoxicities on melanoma cell

Tyrosinase is an enzyme that acts as a catalyst in the biosynthesis of melanin pigment, which is found in fungi, in plants and in animals. Overproduction and accumulation of this pigment causes hyperpigmentation, post inflammatory pigmentation, melasma and skin aging. It also causes to darken the color of foods and fall their quality. Kojic acid (5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) is a well-known compound with its antityrosinase property as well as antibacterial and antifungal properties. It inhibits catecholase activity of tyrosinase, which is the essential enzyme that determines the rate of melanin biosynthesis. However, kojic acid and its many other derivatives have low lipid solubility and lack of high temperature-resistance. Therefore, the studies conducted to obtain safer new derivatives of kojic acid become important to improve its physical properties and biological activities, as well increase its industrial applications. In the light of this information in this thesis, new twelve compounds having structure of 2-(4-(substitutedphenyl)piperazine-1-yl) methyl-3-hydroxy-6-(piperidine/3-methylpiperidine/4-methylpiperidine)methyl-4H-pyran-4-one synthesized from kojic acid. Their structures were identified by using techniques IR, 1H-NMR, 13C-NMR, mass spectroscopy and elementary analysis. Their tyrosinase enzyme inhibitions were determined by spectroscopic method which uses L-DOPA as the substrate. The compounds tested as tyrosinase inhibitor were then evaluated by Sulforhodamine B (SRB) assay for cytotoxic effects in B16F10 murine melanoma cells and IC50 values were calculated for each compound.