Antioxidant, anti-tyrosinase and anti-melanogenic effects of (E)-2, 3-diphenylacrylic acid derivatives. Issue 11 (1st June 2019)

• Record Type: Journal Article
• Authors: Ullah, Sultan; Park, Yujin; Park, Chaeun; Lee, Sanggwon; Kang, Dongwan; Yang, Jungho; Akter, Jinia; Chun, Pusoon; Moon, Hyung Ryong
• Is Part Of: Bioorganic & medicinal chemistry. Volume 27:Issue 11(2019)
• Page Start: 2192
• Page End: 2200
• Publication Date: 2019-06-01
• Subjects: 2, 3-Diphenylacrylic acid -- Perkin reaction -- Tyrosinase -- Inhibitor -- B16F10 melanoma cells -- Skin whitening; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2019.04.020
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: Fifteen 2, 3-DPA derivatives were designed and synthesized via Perkin reaction. ( Z )-2, 3-DPA derivative (1l′ ) was reported for the first time as a major product. Mushroom tyrosinase and B16F10 cells were used for in vitro studies. 1c significantly decreased the activity of mushroom and cellular tyrosinase. In docking studies, 1c strongly binds to tyrosinase than kojic acid. 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 derivatives1a –1n and one ( Z )-2, 3-DPA-derivative1l′ 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 compound1c (−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 indicate1c is a promising candidate treatment for pigmentation-related diseases and potential skin whitening agents.