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Journal of Natural Medicines

, Volume 71, Issue 4, pp 665–682 | Cite as

Semisynthesis and biological evaluation of prenylated resveratrol derivatives as multi-targeted agents for Alzheimer’s disease

  • Thanchanok Puksasook
  • Shinya Kimura
  • Sarin Tadtong
  • Jutamas Jiaranaikulwanitch
  • Jaturong Pratuangdejkul
  • Worawan Kitphati
  • Khanit Suwanborirux
  • Naoki Saito
  • Veena Nukoolkarn
Original Paper

Abstract

A series of prenylated resveratrol derivatives were designed, semisynthesized and biologically evaluated for inhibition of β-secretase (BACE1) and amyloid-β (Aβ) aggregation as well as free radical scavenging and neuroprotective and neuritogenic activities, as potential novel multifunctional agents against Alzheimer’s disease (AD). The results showed that compound 4b exhibited good anti-Aβ aggregation (IC50 = 4.78 µM) and antioxidant activity (IC50 = 41.22 µM) and moderate anti-BACE1 inhibitory activity (23.70% at 50 µM), and could be a lead compound. Moreover, this compound showed no neurotoxicity along with a greater ability to inhibit oxidative stress on P19-derived neuronal cells (50.59% cell viability at 1 nM). The neuritogenic activity presented more branching numbers (9.33) and longer neurites (109.74 µm) than the control, and was comparable to the quercetin positive control. Taken together, these results suggest compound 4b had the greatest multifunctional activities and might be a very promising lead compound for the further development of drugs for AD.

Graphical Abstract

Keywords

Alzheimer’s disease (AD) Prenylated resveratrol derivatives β-Secretase (BACE1) Amyloid-β (Aβ) aggregation Neuroprotective Neuritogencity 

Notes

Acknowledgements

This project was supported by Mahidol University and the National Research Council of Thailand (NRCT). This work was supported in part by a grant from the Dementia Drug Resource Development Center Project (DRC), the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan (S1511016). We also express their gratitude for research funding from the Meiji Pharmaceutical University Asia/Africa Center for Drug Discovery (MPU-AACDD).

Supplementary material

11418_2017_1097_MOESM1_ESM.docx (1.3 mb)
Supplementary material 1 (DOCX 1355 kb)

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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2017

Authors and Affiliations

  • Thanchanok Puksasook
    • 1
  • Shinya Kimura
    • 2
  • Sarin Tadtong
    • 3
  • Jutamas Jiaranaikulwanitch
    • 4
  • Jaturong Pratuangdejkul
    • 5
  • Worawan Kitphati
    • 6
  • Khanit Suwanborirux
    • 7
  • Naoki Saito
    • 2
  • Veena Nukoolkarn
    • 1
  1. 1.Department of Pharmacognosy, Faculty of PharmacyMahidol UniversityBangkokThailand
  2. 2.Graduate School of Pharmaceutical SciencesMeiji Pharmaceutical UniversityTokyoJapan
  3. 3.Department of Pharmacognosy, Faculty of PharmacySrinakharinwirot UniversityNakhon NayokThailand
  4. 4.Department of Pharmaceutical Sciences, Faculty of PharmacyChiang Mai UniversityChiang MaiThailand
  5. 5.Department of Microbiology, Faculty of PharmacyMahidol UniversityBangkokThailand
  6. 6.Department of Physiology, Faculty of PharmacyMahidol UniversityBangkokThailand
  7. 7.Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Center for Bioactive Natural Products from Marine Organisms and Endophytic Fungi (BNPME)Chulalongkorn UniversityBangkokThailand

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