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Synthesis of natural product-like polyprenylated phenols and quinones: Evaluation of their neuroprotective activities
Institution:1. Chemical Biology Laboratory, Graduate School of Arts and Sciences, Iwate University, Morioka 020-8550, Japan;2. Hiroshima Research Center for Healthy Aging, Hiroshima University, Higashi-Hiroshima 739-8530, Japan;3. Division of Biological and Life Sciences, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima 739-8530, Japan;4. RIKEN Center for Sustainable Resource Science, Wako 351-0198, Japan;5. Department of Biological Chemistry and Food Science, Iwate University, Morioka 020-8550, Japan;1. Guizhou Engineering Center for Innovative Traditional Chinese Medicine and Ethnic Medicine, Guizhou University, Guiyang 550025, China;2. Adverse Drug Reaction Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China;1. Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan;2. Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh;3. Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh;4. Temko Corporation, 4-27-4 Honcho, Nakano, Tokyo 164-0012, Japan;5. Faculty of Agriculture, Khon Kaen University, Khon Kaen 40002, Thailand
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:Fungal metabolites  Neogrifolin  Derivatization  MAO-B  SH-SY5Y cells
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