Novel virtual screening approach for the discovery of human tyrosinase inhibitors

• Published in: PloS one Vol. 9; no. 11; p. e112788
• Main Authors: Ai, Ni, Welsh, William J, Santhanam, Uma, Hu, Hong, Lyga, John
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.11.2014; Public Library of Science (PLoS)
• Subjects: Agaricales - chemistry; Agaricales - enzymology; Algorithms; Analysis; Animals; Browning; Catalysis; Catalytic activity; Cell Line, Tumor; Charge distribution; Computer and Information Sciences; Computer applications; Cosmetics; Crystal structure; Dermatological agents; Drug Discovery; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Enzymes; Fungal Proteins - antagonists & inhibitors; Fungal Proteins - chemistry; High-Throughput Screening Assays; Histograms; Humans; Inhibitors; Kinases; Ligands; Medical screening; Medicine and Health Sciences; Melanoma, Experimental - enzymology; Melanoma, Experimental - pathology; Mice; Molecular Docking Simulation; Molecular structure; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - chemistry; Pigmentation; Pigmentation - drug effects; Product development; Proteins; Pyrones - pharmacology; Queries; R&D; Research & development; Screening; Signatures; Skin; Skin - drug effects; Skin - enzymology; Skin - pathology; Skin Lightening Preparations - chemistry; Skin Lightening Preparations - pharmacology; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology; Static Electricity; Structure-Activity Relationship; Studies; Surface charge; Tyrosinase; User-Computer Interface; Vegetables; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112788

Tyrosinase is the key enzyme involved in the human pigmentation process, as well as the undesired browning of fruits and vegetables. Compounds inhibiting tyrosinase catalytic activity are an important class of cosmetic and dermatological agents which show high potential as depigmentation agents used for skin lightening. The multi-step protocol employed for the identification of novel tyrosinase inhibitors incorporated the Shape Signatures computational algorithm for rapid screening of chemical libraries. This algorithm converts the size and shape of a molecule, as well its surface charge distribution and other bio-relevant properties, into compact histograms (signatures) that lend themselves to rapid comparison between molecules. Shape Signatures excels at scaffold hopping across different chemical families, which enables identification of new actives whose molecular structure is distinct from other known actives. Using this approach, we identified a novel class of depigmentation agents that demonstrated promise for skin lightening product development.