2. Academic Validation
  3. Synthesis and evaluation of coumarin derivatives on antioxidative, tyrosinase inhibitory activities, melanogenesis, and in silico investigations

Synthesis and evaluation of coumarin derivatives on antioxidative, tyrosinase inhibitory activities, melanogenesis, and in silico investigations

  • Sci Rep. 2024 Mar 6;14(1):5535. doi: 10.1038/s41598-024-54665-x.
Kasemsiri Chandarajoti 1 2,  Jiraporn Kara 1 3,  Paptawan Suwanhom 1 3,  Teerapat Nualnoi 2 4,  Jindaporn Puripattanavong 5,  Vannajan Sanghiran Lee 6,  Varomyalin Tipmanee 7,  Luelak Lomlim 8 9
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand.
  • 2 Drug Delivery System Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla, 90112, Thailand.
  • 3 Phytomedicine and Pharmaceutical Biotechnology Excellent Center (PPBEC), Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, 90112, Thailand.
  • 4 Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand.
  • 5 Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand.
  • 6 Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
  • 7 Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla, 90112, Thailand.
  • 8 Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand. luelak.l@psu.ac.th.
  • 9 Phytomedicine and Pharmaceutical Biotechnology Excellent Center (PPBEC), Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, 90112, Thailand. luelak.l@psu.ac.th.
PMID: 38448547 DOI: 10.1038/s41598-024-54665-x
Abstract

New coumarin derivatives were designed using a 2-(2-oxo-2H-chromen-4-yl)acetic acid scaffold conjugated with amino acid esters or tyramine. The anti-tyrosinase and anti-lipid peroxidation activities of the synthesized compounds were investigated. Coumarin derivatives 7,9, 11-13, 15-18 showed strong anti-lipid peroxidation activity. Compound 13 exhibited uncompetitive Tyrosinase inhibitory activity with an IC50 value of 68.86 µM. Compound 14 (% activity = 123.41) showed stronger Tyrosinase activating activity than 8-methoxypsolaren (8-MOP, % activity = 109.46). In silico studies revealed different poses between the inhibitors and activators near the Tyrosinase catalytic site. Compounds 13 (25-50 μM) and 14 (25-100 μM) did not show cytotoxicity against B16F10 cells. In contrast to the Tyrosinase inhibition assay, compound 13 (50 μM) suppressed melanogenesis in B16F10 cells with two times higher potency than KA (100 μM). Compound 14 at 100 μM showed melanogenesis enhancement in B16F10 cells in a dose-dependent manner, however, inferior to the 8-MOP. Based on the findings, compound 13 and 14 offer potential for development as skin-lightening agents and vitiligo therapy agents, respectively.

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