Antioxidant, anti-tyrosinase and anti-melanogenic effects of (E)-2,3-diphenylacrylic acid derivatives.

Abstract

During our continued search for strong skin whitening agents over the past ten years, we have investigated the efficacies of many tyrosinase inhibitors containing a common (E)-β-phenyl-α,β-unsaturated carbonyl scaffold, which we found to be essential for the effective inhibition of mushroom and mammalian tyrosinases. In this study, we explored the tyrosinase inhibitory effects of 2,3-diphenylacrylic acid (2,3-DPA) derivatives, which also possess the (E)-β-phenyl-α,β-unsaturated carbonyl motif. We synthesized fourteen (E)-2,3-DPA derivatives 1a-1n and one (Z)-2,3-DPA-derivative 1l' using a Perkin reaction with phenylacetic acid and appropriate substituted benzaldehydes. In our mushroom tyrosinase assay, 1c showed higher tyrosinase inhibitory activity (76.43 ± 3.53%, IC50 = 20.04 ± 1.91 µM) with than the other 2,3-DPA derivatives or kojic acid (21.56 ± 2.93%, IC50 = 30.64 ± 1.27 μM). Our mushroom tyrosinase inhibitory results were supported by our docking study, which showed compound 1c (-7.2 kcal/mole) exhibited stronger binding affinity for mushroom tyrosinase than kojic acid (-5.7 kcal/mole). In B16F10 melanoma cells (a murine cell-line), 1c showed no cytotoxic effect up to a concentration of 25 μM and exhibited greater tyrosinase inhibitory activity (68.83%) than kojic acid (49.39%). In these cells, arbutin (a well-known tyrosinase inhibitor used as the positive control) only inhibited tyrosinase by 42.67% even at a concentration of 400 μM. Furthermore, at 25 µM, 1c reduced melanin contents in B16F10 melanoma cells by 24.3% more than kojic acid (62.77% vs. 38.52%). These results indicate 1c is a promising candidate treatment for pigmentation-related diseases and potential skin whitening agents.

• Authors: Sultan Ullah, Yujin Park, Chaeun Park, Sanggwon Lee, Dongwan Kang, Jungho Yang, Jinia Akter, Pusoon Chun, Hyung Ryong Moon
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 27 Issue 11 Pg. 2192-2200 (06 01 2019) ISSN: 1464-3391 [Electronic] England
• PMID: 31027707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Cinnamates
• Enzyme Inhibitors
• Free Radical Scavengers
• Pyrones
• Skin Lightening Preparations
• Stilbenes
• kojic acid
• Monophenol Monooxygenase

Topics

• Agaricus (enzymology)
• Animals
• Catalytic Domain
• Cell Line, Tumor
• Cinnamates (chemical synthesis, metabolism, pharmacology, toxicity)
• Enzyme Inhibitors (chemical synthesis, metabolism, pharmacology, toxicity)
• Free Radical Scavengers (chemical synthesis, metabolism, pharmacology, toxicity)
• Mice
• Molecular Docking Simulation
• Monophenol Monooxygenase (chemistry, metabolism)
• Protein Binding
• Pyrones (chemistry, metabolism)
• Skin Lightening Preparations (chemical synthesis, metabolism, pharmacology, toxicity)
• Stilbenes (chemical synthesis, metabolism, pharmacology, toxicity)