In vitro anti-melanogenic effects of chimeric compounds, 2-(substituted benzylidene)-1,3-indanedione derivatives with a β-phenyl-α, β -unsaturated dicarbonyl scaffold

• Published in: Bioorganic chemistry 2021-04, Vol.109, p.104688-104688, Article 104688
• Main Authors: Ryu, Il Young, Choi, Inkyu, Jung, Hee Jin, Ullah, Sultan, Choi, Heejeong, Al-Amin, Md, Chun, Pusoon, Moon, Hyung Ryong
• Format: Article
• Language: English
• Subjects: Anti-melanogenic effect; Chimeric compound; Competitive inhibitor; Docking simulation; Indanedione; Kojic acid; Tyrosinase inhibitor; β-phenyl-α; β-unsaturated dicarbonyl
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.104688

[Display omitted] •Indanedione derivatives were synthesized as chimeric compounds.•2 and 3 showed much stronger mushroom tyrosinase inhibitory activity than kojic acid.•Results of kinetic studies results supported that 2 and 3 are competitive inhibitors.•2 and 3 exhibited stronger cellular tyrosinase inhibitory activity than kojic acid.•In B16F10 cells, compounds 2 and 3 reduced melanin contents more than kojic acid.•β-Phenyl-α,β-unsaturated dicarbonyl compounds are promising tyrosinase inhibitors. Tyrosinase is considered a key contributor to melanogenesis, and safe, potent tyrosinase inhibitors are needed for medical and cosmetic purposes to treat skin hyperpigmentation and prevent fruit and vegetable browning. According to our accumulated SAR data on tyrosinase inhibitors, the β-phenyl-α,β-unsaturated carbonyl scaffold in either E or Z configurations, can confer potent tyrosinase inhibitory activity. In this study, twelve indanedione derivatives were synthesized as chimeric compounds with a β-phenyl-α,β-unsaturated dicarbonyl scaffold. Two of these derivatives, that is, compounds 2 and 3 (85% and 96% inhibition, respectively), at 50 μM inhibited mushroom tyrosinase markedly more potently than kojic acid (49% inhibition). Docking studies predicted that compounds 2 and 3 both inhibited tyrosinase competitively, and these findings were supported by Lineweaver-Burk plots. In addition, both compounds inhibited tyrosinase activity and reduced melanin contents in B16F10 cells more than kojic acid without perceptible cytotoxicity. These results support the notion that chimeric compounds with the β-phenyl-α,β-unsaturated dicarbonyl scaffold represent promising starting points for the development of potent tyrosinase inhibitors.