Development of Predictive Pharmacophore Model for Tyrosinase Inhibitors Derived from Screening Herbal Compounds

• Main Authors: Bo-Chang Liao, 廖柏錩
• Other Authors: Nai-Wan Hsiao
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/12093990032203469031

碩士 === 國立彰化師範大學 === 生物技術研究所 === 100 === Tyrosinase (EC 1.14.18.1) is an oxidase with copper, widely distributed in microorganisms, plants and animal body, is an enzyme that plays a very important role in melanin synthesis. Melanin in mammalians can protect the skin from UV-induced injury by absorbing UV light. However, melanin was not metabolized timely and accumulated in the skin, it might cause dark spots or freckles and might cause melanoma. Tyrosinase is the rate-limiting enzyme in melanin biosynthesis. It catalyzes the reaction of the hydroxylation of tyrosine to Dopa and the oxidation of dopa to dopaquinone. In order to inhibit biosynthesis of melanin, the primary method is to inhibit tyrosinase activity. The whitening ingredients currently available in the market are mostly chemically synthesized and over-dosing could easily cause many side effects. A recent study has shown that arbutin is metabolized to produce hydroquinone and kojic acid, both of which are known carcinogens and are banned in Japan and other foreign countries. In the trend of using natural medicines to reduce side effects, the use of herbal compounds and peptides as raw materials or additives is surely more safe and attractive. Therefore, we collected a variety of 297 TCM compounds derived from 78 different Traditional Chinese Herbs. In the same experimental condition, we tested these compounds’ inhibition for tyrosinase activity and obtained the values of IC50. We used the common additives kojic acid, α-arbutin and β-arbutin as positive control. According to the experimental result, the inhibitory tyrosinase activity of 3 compounds are better than kojic acid, and the inhibitory tyrosinase activity of 19 compounds are between kojic acid andβ-arbutin, and the inhibitory tyrosinase activity of 17 compounds are between β-arbutin and α-arbutin. And then, we could build pharmacophore model by combining the known structures and the values of IC50 to find out the different structural features between tyrosinase and compounds.