Synthesis of natural product-like polyprenylated phenols and quinones: Evaluation of their neuroprotective activities

  • Bioorg Med Chem. 2020 Jan 1;28(1):115156. doi: 10.1016/j.bmc.2019.115156.
Hitoshi Kamauchi  1 ,  Takumi Oda  2 ,  Kanayo Horiuchi  2 ,  Koichi Takao  2 ,  Yoshiaki Sugita  2
Affiliations
  • 1. Laboratory of Bioorganic Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyaki-dai, Sakado, Saitama 350-0295, Japan. Electronic address: [email protected].
  • 2. Laboratory of Bioorganic Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyaki-dai, Sakado, Saitama 350-0295, Japan.
PMID: 31740200 DOI: 10.1016/j.bmc.2019.115156
Abstract

Twenty-seven natural product-like polyprenylated Phenols and Quinones were synthesized and their neuroprotective activity was tested using human Monoamine Oxidase B (MAO-B) and SH-SY5Y cells. Eight compounds inhibited MAO-B (IC50 values < 25 μM) and the inhibition mode and molecular docking of two (8c and 16c) were investigated. Compounds inhibiting MAO-B activity were additionally tested for their ability to protect SH-SY5Y cells from peroxide injury. Three derivatives (3c, 8c and 16c) exhibited both MAO-B inhibitory and neuroprotective activity. A structure activity-relationship study showed that a phenolic hydroxyl group and a longer side chain are important for both activities.

Keywords
Derivatization; Fungal metabolites; MAO-B; Neogrifolin; SH-SY5Y cells.
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