Planta Med 2007; 73(14): 1478-1481
DOI: 10.1055/s-2007-990245
Pharmacology
Letter
© Georg Thieme Verlag KG Stuttgart · New York

Decursin and Decursinol Angelate Selectively Inhibit NADH-Fumarate Reductase of Ascaris suum

Kazuro Shiomi1 , 2 , Hiroko Hatano2 , Hiromi Morimoto3 , Hideaki Ui1 , Kimitoshi Sakamoto4 , Kiyoshi Kita4 , Hiroshi Tomoda3 , Eun Woo Lee5 , Tae Ryeon Heo6 , Hirokazu Kawagishi7 , Satoshi  Omura1 , 2
  • 1Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan
  • 2The Kitasato Institute, Tokyo, Japan
  • 3School of Pharmacy, Kitasato University, Tokyo Japan
  • 4Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • 5PNE Co. Ltd., 907-12 Daechidong, Kangnam-Gu, Seoul, Korea
  • 6Faculty of Biological Engineering, Inha University, Incheon, Korea
  • 7Graduate School of Science and Technology, Shizuoka University, Shizuoka, Japan
Further Information

Publication History

Received: August 24, 2006 Revised: May 8, 2007

Accepted: July 6, 2007

Publication Date:
18 October 2007 (online)

Abstract

NADH-fumarate reductase (NFRD) is a key enzyme in many anaerobic helminths. Decursin and decursinol angelate have been isolated from the roots of Angelica gigas Nakai (Apiaceae) as NFRD inhibitors. They inhibited Ascaris suum NFRD with IC50 values of 1.1 and 2.7 μM, respectively. Their target is the electron transport enzyme complex I. Since the inhibitory activities of decursin against bovine heart complexes are weak, it is a selective inhibitor of the nematode complex I. In contrast, decursinol angelate moderately inhibits bovine heart complexes II and III. Decursinol inhibits A. suum NFRD to a similar extent, but its target is complex II. It also inhibits bovine heart complexes II and III.

References

  • 1 Kita K, Nihei C, Tomitsuka E. Parasite mitochondria as drug target: diversity and dynamic changes during the life cycle.  Curr Med Chem. 2003;  10 2535-48.
  • 2 O-mura S, Miyadera H, Ui H, Shiomi K, Yamaguchi Y, Masuma R. et al . An anthelmintic compound, nafuredin, shows selective inhibition of complex I in helminth mitochondria.  Proc Natl Acad Sci USA. 2001;  98 60-2.
  • 3 Ui H, Shiomi K, Yamaguchi Y, Masuma R, Nagamitsu T, Takano D. et al . Nafuredin, a novel inhibitor of NADH-fumarate reductase, produced by Aspergillus niger FT-0554.  J Antibiot. 2001;  54 234-8.
  • 4 Shiomi K, Ui H, Suzuki H, Hatano H, Nagamitsu T, Takano D. et al . A γ-lactone form nafuredin, nafuredin-γ, also inhibits helminth complex I. J.  Antibiot. 2005;  58 50-5
  • 5 Miyadera H, Shiomi K, Ui H, Yamaguchi Y, Masuma R, Tomoda H. et al . Atpenins, potent and specific inhibitors of mitochondrial complex II (succinate-ubiquinone oxidoreductase).  Proc Natl Acad Sci USA. 2003;  100 473-7.
  • 6 Horsefield R, Yankovskaya V, Sexton G, Whittingham W, Shiomi K, O-mura S. et al . Structural and computational analysis of the quinone-binding site of complex II (succinate-ubiquinone oxidoreductase): a mechanism of electron transfer and proton conduction during ubiquinone reduction.  J Biol Chem. 2006;  281 7309-16.
  • 7 Hata K, Sano K. Constitution of decursin, a new coumarin isolated from the root of Angelica decursiva . Tetrahedron Lett 1966: 1461-5
  • 8 Ryu K S, Yook C S. Coumarins of the root of Angelica gigas. I.  J Pharmaceut Soc Korea. 1967;  11 22-6.
  • 9 Ryu K S, Hong N D, Kim N J, Kong Y Y. Studies on the coumarin constituents of the root of Angelica gigas Nakai. Isolation of decursinol angelate and assay of decursinol angelate and decursin.  Kor J Pharmacol. 1990;  21 64-8.
  • 10 Okuyama T, Takata M, Nishino H, Nishino A, Takayasu J, Iwashima A. Studies on the antitumor-promoting activity of naturally-occurring substances. III. Structure of a new coumarin and antitumor-promoter activity of coumarins from Angelicae Radix .  Shoyakugaku Zasshi. 1990;  44 346-8.
  • 11 Bae E A, Han M J, Kim N J, Kim D H. Anti-Helicobacter pylori activity of herbal medicines.  Biol Pharm Bull. 1998;  21 990-2.
  • 12 Lee S, Lee Y S, Jung S H, Shin K H, Kim B K, Kang S S. Anti-tumor activities of decursinol angelate and decursin from Angelica gigas .  Arch Pharm Res. 2003;  26 727-30.
  • 13 Ahn K S, Sim W S, Kim I H. Decursin: a cytotoxic agent and protein kinase C activator from the root of Angelica gigas .  Planta Med. 1996;  62 7-9.
  • 14 Ahn K S, Sim W S, Lee I K, Seu Y B, Kim I H. Decursinol angelate. A cytotoxic and protein kinase C activating agent from the root of Angelica gigas .  Planta Med. 1997;  63 360-1.
  • 15 Rho T C, Choi H C, Lee S W, Kim Y H, Rho M C, Kim Y K. et al . Inhibition of nitric oxide synthesis by coumarins from Polygonum cuspidatum in LPS-activated RAW 264.7 cells.  Saengyak Hakhoechi. 2001;  32 181-8.
  • 16 Chun H S, Lee C B. Changes of chloroplast-mediated electron transport activity and chlorophyll-protein complexes in barley seedlings by decursinol.  Kor J Bot. 1988;  31 131-41.
  • 17 Lee C B, Lee M J, Chi H J, Kwon Y M. Effects of decursin and decursinol on the germination and growth of plants.  Kor J Bot. 1976;  19 7-13.
  • 18 Moon C K, Lee S C, Yun Y P, Ha B J, Yook C S. Effects of some coumarin derivatives on the bovine lens aldose reductase activity.  Arch Pharm Res. 1988;  11 308-11.
  • 19 Chen M, Andersen L P, Zhai L, Kharazmi A. Characterization of the respiratory chain of Helicobacter pylori .  FEMS Immunol Med Microbiol. 1999;  24 169-74.
  • 20 Nemoto T, Ohshima T, Shibasaki M. Enantioselective total syntheses of (+)-decursin and related natural compounds using catalytic asymmetric epoxidation of an enone.  Tetrahedron. 2003;  59 6889-97.

Prof. Kazuro Shiomi

Kitasato Institute for Life Sciences

Kitasato University

5-9-1 Shirokane

Minato-ku

Tokyo 108-8641

Japan

Phone: +81-3-5791-6439

Fax: +81-3-5791-6131

Email: shiomi@lisci.kitasato-u.ac.jp

    >