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Pharmacophore Modeling for Targets with Extensive Ligand Libraries: A Case Study on SARS-CoV-2 Mpro
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A Combination of Pharmacophore and Docking-based Virtual Screening to Discover new Tyrosinase Inhibitors
Serena Vittorio1,2, Thomas Seidel2, Maria Paola Germanò1
1Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Palatucci, 98168, Messina, Italy.
Abstract:
Melanogenesis controls the formation of melanin pigment whose overproduction is related to various hyperpigmentary disorders in humans. Tyrosinase is a type-3 copper enzyme involved in the rate limiting step of melanin synthesis, therefore its inhibition could represent an efficient way for the development of depigmenting agents. In this work, a combination of pharmacophore and docking-based studies has been employed to screen two in-house 3D compound databases containing about 2,000 molecules from natural and synthetic sources. As result we selected two "hit compounds" which proved to inhibit tyrosinase activity showing IC50 values in the micromolar range.
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