Novel tyrosinase inhibitors from natural resources - their computational studies

Tyrosinase is a multi-copper enzyme widely distributed in different organisms, including plants & mammals, etc., which is responsible for pigmentations, undesired browning of fruits and vegetables. This is the key enzyme in the melanogenesis in human and molting process of insects. Therefore the inhibitors of the enzyme may lead to novel skin whitening agents, anti-browning substances or compounds for insect control. A large numbers of moderate to potent tyrosinase inhibitors have been reported during the last decade. From our group, we reported a number of potent inhibitors from synthetic, semi-synthetic and natural origins. The compounds are from several chemical classes, like phenolics, terpenes, steroids, chalcones, flavonoids, alkaloids, long-chain fatty acids, coumarins, sildenafil analogs, bipiperidines, biscoumarins, oxadiazole, tetraketones, etc. More recently, the crystal structure of mushroom and couple of other tyrosinases has been published and more recently the crystal structure of mushroom tyrosinase complexes with a highly potent inhibitor tropolone has been reported. Yet there is a lack of information of inhibitor-tyrosinase intermolecular interactions. To overcome such issues, some researchers started utilizing in silico tools, like molecular docking simulations, for such purposes. There are also few papers published about the successful utilization of computational tools like QSAR-based and ligand-based virtual screening to identify novel and potent inhibitors of the enzyme. In our group, we are using all possible computational tools, like ligand-based as well structure-based approaches, to identify new inhibitors. In this review, some of such examples are briefly described.