Inhibitory effects of benzyl benzoate and its derivatives on angiotensin II-induced hypertension

Osamu Ohno, Mao Ye, Tomoyuki Koyama, Kazunaga Yazawa, Emi Mura, Hiroshi Matsumoto, Takao Ichino, Kaoru Yamada, Kazuhiko Nakamura, Tomohiro Ohno, Kohji Yamaguchi, Junji Ishida, Akiyoshi Fukamizu, Daisuke Uemura

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20 Citations (Scopus)

Abstract

Hypertension is a lifestyle-related disease which often leads to serious conditions such as heart disease and cerebral hemorrhage. Angiotensin II (Ang II) plays an important role in regulating cardiovascular homeostasis. Consequently, antagonists that block the interaction of Ang II with its receptors are thought to be effective in the suppression of hypertension. In this study, we searched for plant compounds that had antagonist-like activity toward Ang II receptors. From among 435 plant samples, we found that EtOH extract from the resin of sweet gum Liquidambar styraciflua strongly inhibited Ang II signaling. We isolated benzyl benzoate and benzyl cinnamate from this extract and found that those compounds inhibited the function of Ang II in a dose-dependent manner without cytotoxicity. An in vivo study showed that benzyl benzoate significantly suppressed Ang II-induced hypertension in mice. In addition, we synthesized more than 40 derivatives of benzyl benzoate and found that the meta-methyl and 3-methylbenzyl 2′-nitrobenzoate derivatives showed about 10-fold higher activity than benzyl benzoate itself. Thus, benzyl benzoate, its derivatives, and benzyl cinnamate may be useful for reducing hypertension.

Original languageEnglish
Pages (from-to)7843-7852
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number16
DOIs
Publication statusPublished - 2008 Aug 15

Keywords

  • Angiotensin II
  • Benzyl benzoate
  • Benzyl cinnamate
  • Hypertension
  • Liquidambar styraciflua
  • Losartan

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Ohno, O., Ye, M., Koyama, T., Yazawa, K., Mura, E., Matsumoto, H., Ichino, T., Yamada, K., Nakamura, K., Ohno, T., Yamaguchi, K., Ishida, J., Fukamizu, A., & Uemura, D. (2008). Inhibitory effects of benzyl benzoate and its derivatives on angiotensin II-induced hypertension. Bioorganic and Medicinal Chemistry, 16(16), 7843-7852. https://doi.org/10.1016/j.bmc.2008.03.056