A Combination of Pharmacophore and Docking‐based Virtual Screening to Discover new Tyrosinase Inhibitors. Issue 3 (11th September 2019)

• Record Type: Journal Article
• Authors: Vittorio, Serena; Seidel, Thomas; Germanò, Maria Paola; Gitto, Rosaria; Ielo, Laura; Garon, Arthur; Rapisarda, Antonio; Pace, Vittorio; Langer, Thierry; De Luca, Laura
• Is Part Of: Molecular informatics. Volume 39:Issue 3(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-09-11
• Subjects: Tyrosinase -- Ty Inhibitors -- Pharmacophore model -- LigandScout -- Docking studies.; Cheminformatics -- Periodicals; QSAR (Biochemistry) -- Periodicals; Structure-activity relationships (Biochemistry) -- Periodicals; Drugs -- Structure-activity relationships -- Periodicals; 615.19
• DOI: 10.1002/minf.201900054
• Languages: English
• ISSNs: 1868-1743

Abstract

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. Abstract : A structure‐based pharmacophore model for tyrosinase catalytic pocket was built for the first time combining features deriving from the protein‐ligand complex and the enzyme apo‐structure. The generated model was used to screen two in‐house 3D databases containing about 2000 molecules and docking studies were subsequently conducted for the hits retrieved from the virtual screening. Two compounds were selected and tested proving to be active at micromolar concentration.