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Five new 2-(2-phenylethyl)chromone derivatives from agarwood

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Abstract

Agarwood has been used as an incense and in traditional medicines as aphrodisiac, sedative, cardiotonic, and carminative. In this study, five new 2-(2-phenylethyl)chromones (2, 13–16) and eleven known compounds (1, 3–12) were isolated from the agarwood. The structures of the new compounds were determined by 1H-, 13C-, and two-dimensional NMR together with electronic circular dichroism (ECD) spectroscopy. All isolated compounds were evaluated for the phosphodiesterase (PDE) 3A and 5A1 inhibitory activity by the fluorescence polarization method. Dimeric 2-(2-phenylehyl)chromones (13, 14, 16) had potent inhibitory activity to PDE 5A1 with IC50 values of micro molar range (13: 4.2 μM, 14: 7.9 μM, 16: 4.3 μM), whereas they had weak activity to PDE 3A. In contrast, compound (15), which has a phenylpropionic acid moiety instead of the 2-(2-phenylethyl)chromone moiety in the dimers, showed moderate inhibition of both PDE 3A (IC50: 42.6 μM) and PDE 5A1 (IC50: 15.1 μM).

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References

  1. The Japanese standards for non-pharmacopoeial crude drugs 2018, The Ministry of Health Labour and Welfare, Japan

  2. Gao M, Han X, Sun Y, Chen H, Yang Y, Liu Y, Meng H, Gao Z, Xu Y, Zhang Z, Han J (2019) Overview of sesquiterpenes and chromones of agarwood originating from four main species of the genus Aquilaria. RSC Adv 9:4113–4130

    Article  CAS  Google Scholar 

  3. Nikpour M, Sadeghian H, Saberi MR, Nick RS, Seyedi SM, Hosseini A, Parsaee H, Bozorg ATD (2010) Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors. Bioorg Med Chem 18:855–862

    Article  CAS  Google Scholar 

  4. Sawant SD, Reddy GL, Dar MI, Srinivas M, Gupta G, Sahu PK, Mahajan P, Nargotra A, Singh S, Sharma SC, Tikoo M, Singh G, Vishwakarma RA, Syed SH (2015) Discovery of novel pyrazolopyrimidinone analogs as potent inhibitors of phosphodiesterase type-5. Bioorg Med Chem 23:2121–2128

    Article  CAS  Google Scholar 

  5. Sugiyama T, Narukawa Y, Shibata S, Masui R, Kiuchi F (2016) New 2-(2-phenylethyl)chromone derivatives and inhibitors of phosphodiesterase (PDE) 3A from agarwood. Nat Prod Commn 11:795–797

    Google Scholar 

  6. Sugiyama T, Narukawa Y, Shibata S, Masui R, Kiuchi F (2018) Three new 5,6,7,8-tetrahydroxy-5,6,7,8-tetrahydrochromone derivatives enantiomeric to agarotetrol from agarwood. J Nat Med 72:667–674

    Article  CAS  Google Scholar 

  7. Yang L, Qiao L, Xie D, Yuan Y, Chen N, Dai J, Guo S (2012) 2-(2-phenylethylchromones from Chinese eaglewood. Phytochemistry 76:92–97

    Article  CAS  Google Scholar 

  8. Yagura T, Ito M, Kiuchi F, Honda G, Shimada Y (2003) Four new 2-(2-phenylethyl) chromone derivatives from withered wood of Aquilaria sinensis. Chem Pharm Bull 51:560–564

    Article  CAS  Google Scholar 

  9. Konishi T, Konoshima T, Shimada Y, Kiyosawa S (2002) Six new 2- (2-phenylethyl)chromone from Agarwood. Chem Pharm Bull 50:419–422

    Article  CAS  Google Scholar 

  10. Shimada Y, Konishi T, Kiyosawa S, Nishi M, Miyahara K, Kawasaki T (1986) Studies on the agarwood (Jinko) IV, Structures of 2-(2-phenyl- ethyl)chromone derivatives, agarotetrol and isoagarotetrol. Chem Pharm Bull 34:2766–2773

    Article  CAS  Google Scholar 

  11. Chen D, Xu Z, Chai X, Zeng K, Jia Y, Bi D, Ma Z, Tu P (2012) Nine 2-(2-phenylethyl)chromone derivatives from the resinous wood of Aquilaria sinensis and their inhibition of LPS-induced NO production in RAW 264.7 cells. Eur J Org Chem 2012:5389–5397

    Article  CAS  Google Scholar 

  12. Yoshii E, Koizumi T, Oribe T (1978) The structure of agarotetrol, a novel highly oxygenated chromone from agarwood (Jinko). Tetrahedron Lett 41:3921–3924

    Article  Google Scholar 

  13. Kumazawa S, Kanda M, Utagawa M, Chiba N, Ohtani H, Misawa T (2003) MK7924, a novel metabolite with nematocidal activity from Coronophora gregaria. J Antibiot 56:652–654

    Article  CAS  Google Scholar 

  14. Xiang P, Mei W, Chen H, Kong F, Wang H, Liao G, Zhou L, Dai H (2017) Four new bi-phenylethylchromones from artificial agarwood. Fioterapia 120:61–66

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by Keio Gijyuku Academic Development Funds and MEXT-Supported Program for the Strategic Research Foundation at Private Universities.

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Authors and Affiliations

  1. Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan

    Shunsuke Shibata, Takuji Sugiyama, Yoshinori Uekusa, Yuji Narukawa & Fumiyuki Kiuchi

  2. Tokyo Research Center, Kyushin Pharmaceutical Co. Ltd, 1-22-10 Wada, Suginami-ku, Tokyo, 166-0012, Japan

    Ryo Masui

Authors
  1. Shunsuke Shibata
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  2. Takuji Sugiyama
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  3. Yoshinori Uekusa
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  4. Ryo Masui
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  5. Yuji Narukawa
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  6. Fumiyuki Kiuchi
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Correspondence to Yuji Narukawa.

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Shibata, S., Sugiyama, T., Uekusa, Y. et al. Five new 2-(2-phenylethyl)chromone derivatives from agarwood. J Nat Med 74, 561–570 (2020). https://doi.org/10.1007/s11418-020-01410-z

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  • DOI: https://doi.org/10.1007/s11418-020-01410-z

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