Novel Virtual Screening Approach for the Discovery of Human Tyrosinase Inhibitors

Abstract

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.

Chemotypic Characterization and Biological Activity of Rosmarinus officinalis

“…In vitro mushroom tyrosinase inhibitory activity of R. officinalis oil from Yemen was determined by a spectrophotometric approach using l -tyrosine as the substrate [84]. In a total volume of 200 µL, the enzyme activity was measured in buffer containing 50 mM phosphate buffer, pH 6.5, 50 U/mL mushroom tyrosinase, and 50 µg/mL l -tyrosine.…”

Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors

“…Thus compound 36 is a potential candidate in developing safe and effective pharmacological agent for skin-whitening. Recently, Ai et al., screened a chemical library using a virtual screening approach and identified a compound 41 as a potent mushroom tyrosinase inhibitor 125 , with an IC 50 value of 8 μM and yielded a 29%±17.64% blockage of melanin biosynthesis in B16 cells at a concentration of 0.002% that was equal to 27.5 μM.…”

Chemical Composition and Biological Activity of the Essential Oil Isolated from the Leaves of Achillea fragrantissima Growing Wild in Yemen

“…In vitro mushroom tyrosinase inhibitory activity of A. fragrantissima oil from Yemen was determined by a spectrophotometric approach using L-tyrosine as the substrate. 23 In a total volume of 200 μL, the enzyme activity was measured in buffer containing 50 mM phosphate buffer, pH 6.5, 50 U/mL mushroom tyrosinase and 50 μg/mL L-tyrosine. The reaction (conversion of L-tyrosine to DOPAchrome) was conducted at 37°C for 30 min and absorbance was measured at 490 nm using a microplate reader in the presence and absence of 100 μg/mL of AFEO.…”