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Archives of Pharmacal Research

, Volume 39, Issue 7, pp 897–911 | Cite as

New ursane triterpenoids from Ficus pandurata and their binding affinity for human cannabinoid and opioid receptors

  • Amgad I. M. Khedr
  • Sabrin R. M. IbrahimEmail author
  • Gamal A. Mohamed
  • Hany E. A. Ahmed
  • Amany S. Ahmad
  • Mahmoud A. Ramadan
  • Atef E. Abd El-Baky
  • Koji Yamada
  • Samir A. Ross
Research Article

Abstract

Phytochemical investigation of Ficus pandurata Hance (Moraceae) fruits has led to the isolation of two new triterpenoids, ficupanduratin A [1β-hydroxy-3β-acetoxy-11α-methoxy-urs-12-ene] (11) and ficupanduratin B [21α-hydroxy-3β-acetoxy-11α-methoxy-urs-12-ene] (17), along with 20 known compounds: α-amyrin acetate (1), α-amyrin (2), 3β-acetoxy-20-taraxasten-22-one (3), 3β-acetoxy-11α-methoxy-olean-12-ene (4), 3β-acetoxy-11α-methoxy-12-ursene (5), 11-oxo-α-amyrin acetate (6), 11-oxo-β-amyrin acetate (7), palmitic acid (8), stigmast-4,22-diene-3,6-dione (9), stigmast-4-ene-3,6-dione (10), stigmasterol (12), β-sitosterol (13), stigmast-22-ene-3,6-dione (14), stigmastane-3,6-dione (15), 3β,21β-dihydroxy-11α-methoxy-olean-12-ene (16), 3β-hydroxy-11α-methoxyurs-12-ene (18), 6-hydroxystigmast-4,22-diene-3-one (19), 6-hydroxystigmast-4-ene-3-one (20), 11α,21α-dihydroxy-3β-acetoxy-urs-12-ene (21), and β-sitosterol-3-O-β-d-glucopyranoside (22). Compound 21 is reported for the first time from a natural source. The structures of the 20 compounds were elucidated on the basis of IR, 1D (1H and 13C), 2D (1H–1H COSY, HSQC, HMBC and NOESY) NMR and MS spectroscopic data, in addition to comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. In addition, their radioligand displacement affinity on opioid and cannabinoid receptors was assessed. Compounds 4, 11, and 15 exhibited good affinity towards the CB2 receptor, with displacement values of 69.7, 62.5 and 86.5 %, respectively. Furthermore, the binding mode of the active compounds in the active site of the CB2 cannabinoid receptors was investigated through molecular modelling.

Keywords

Ficus pandurata Triterpenes Cannabinoid receptors Opioid receptors Anti-malarial Anti-leishmanial 

Notes

Acknowledgments

We are grateful to Mr. M. Inada, Mr. N. Yamaguchi and Mr. N. Tsuda of the Scientific Support Section of Joint Research Center, Nagasaki University, for 1H NMR, 13C NMR and MS measurements. This work was supported in part by a Grant-in-Aid for Scientific Research [Grant Number 23590008 and 26460124] from the Japan Society for the Promotion of Science, which is gratefully acknowledged. The in vitro binding assay using opioid and cannabinoid receptors was made possible by a grant from the NIGMS, a component of the National Institutes of Health (NIH) [Grant Number P20GM104932]. The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH.

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest with respect to this work.

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Copyright information

© The Pharmaceutical Society of Korea 2016

Authors and Affiliations

  • Amgad I. M. Khedr
    • 1
  • Sabrin R. M. Ibrahim
    • 2
    • 3
    Email author
  • Gamal A. Mohamed
    • 4
    • 5
  • Hany E. A. Ahmed
    • 2
    • 6
  • Amany S. Ahmad
    • 3
  • Mahmoud A. Ramadan
    • 3
  • Atef E. Abd El-Baky
    • 7
  • Koji Yamada
    • 8
  • Samir A. Ross
    • 9
  1. 1.Department of Pharmacognosy, Faculty of PharmacyPort Said UniversityPort SaidEgypt
  2. 2.Department of Pharmacognosy and Pharmaceutical Chemistry, College of PharmacyTaibah UniversityAl Madinah Al MunawarahSaudi Arabia
  3. 3.Department of Pharmacognosy, Faculty of PharmacyAssuit UniversityAssuitEgypt
  4. 4.Department of Natural Products and Alternative Medicine, Faculty of PharmacyKing Abdulaziz UniversityJeddahSaudi Arabia
  5. 5.Department of Pharmacognosy, Faculty of PharmacyAl-Azhar UniversityAssuitEgypt
  6. 6.Pharmaceutical Organic Chemistry Department, Faculty of PharmacyAl-Azhar UniversityCairoEgypt
  7. 7.Department of Biochemistry, Faculty of PharmacyPort Said UniversityPort SaidEgypt
  8. 8.Garden for Medicinal Plants, Graduate School of Biomedical SciencesNagasaki UniversityNagasakiJapan
  9. 9.National Center for Natural Products Research, and Department of Pharmacognosy, School of PharmacyUniversity of MississippiUniversityUSA

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