Melanogenesis-inhibitory activities of limonoids and tricyclic diterpenoids from Azadirachta indica

  • Bioorg Chem. 2020 Jul;100:103941. doi: 10.1016/j.bioorg.2020.103941.
Shengzhi Su  1 ,  Jiaxin Cheng  1 ,  Chaofeng Zhang  1 ,  Toshihiro Akihisa  1 ,  Jian Xu  1 ,  Wanfang Zhu  2 ,  Wenyuan Liu  2 ,  Takashi Kikuchi  3 ,  Feng Feng  4 ,  Jie Zhang  5
Affiliations
  • 1. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
  • 2. School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
  • 3. Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1904, Japan.
  • 4. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Jiangsu Food & Pharmaceutical Science College, Huaian 223003, China. Electronic address: [email protected].
  • 5. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: [email protected].
PMID: 32450387 DOI: 10.1016/j.bioorg.2020.103941
Abstract

The chemical constituents of the roots and bark of Azadirachta indica were investigated, leading to the isolation of six tricyclic Diterpenoids and four limonoids including a new compound, azadirachtin J (4). The structures were elucidated on the basis of NMR spectroscopic techniques, mass spectrometry as well as comparison with the literature. Furthermore, melanogenesis-inhibitory activities of the isolated compounds were evaluated. As a result, compounds 1-3 and 10 exhibited superior inhibitory activities against melanogenesis with no, or almost no, toxicity to the cells (86.5-105.1% cell viability). Western blot analysis showed that compounds 1 and 3 exhibited melanogenesis inhibitory activities in α-MSH-stimulated B16 melanoma cells due to, at least in part, inhibition of the expression of MITF, followed by a decrease in the expression of Tyrosinase, TRP-1, and TRP-2. Compounds 1 and 3 exhibited Tyrosinase inhibitory activities (IC50 values of 44.86 μM and 69.85 μM respectively). Docking results confirm that the active inhibitors strongly interact with Tyrosinase residues.

Keywords
Limonoids; Melanogenesis-inhibitory; Tyrosinase.
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