Planta Med 2007; 73(14): 1481-1485
DOI: 10.1055/s-2007-990249
Pharmacology
Letter
© Georg Thieme Verlag KG Stuttgart · New York

Inhibition of HCV Replicon Cell Growth by 2-Arylbenzofuran Derivatives Isolated from Mori Cortex Radicis

Hyun Yong Lee1 [*] , Ji Hyun Yum1 [*] , Yang Kook Rho1 , Seong Jun Oh1 , Hyun Sik Choi1 , Hwan Bong Chang1 , Dong Hwa Choi1 , Moon-Jeong Leem1 , Eun Joo Choi1 , Jei Man Ryu1 , Soon Bong Hwang2
  • 1R&D Center, Dong-Wha Pharmaceutical Ind. Co. Ltd., Anyang, Korea
  • 2Ilsung Institute of Life Science, Hallym University, Chuncheon, Korea
Further Information

Publication History

Received: May 4, 2007 Revised: September 11, 2007

Accepted: September 16, 2009

Publication Date:
18 October 2007 (online)

Abstract

Medicinal herbs are increasingly used in the search for safe and efficient drug candidates for hepatitis C virus infection. In this study, we have investigated the anti-HCV effect of compounds from Mori Cortex Radicis. During a screening for extracts with anti-HCV affinity from medicinal plants (173 species), the methanol extract of Mori Cortex Radicis was selected. Fractionation of the extract by monitoring antiviral activity with a replicon cell-based assay resulted in the isolation of five compounds, mulberroside C (1), moracin P (2), moracin O (3), moracin M (4) and mulberrofuran K (5) from the ethyl acetate-soluble fraction. Compounds 14 showed significant inhibitory activities. Compounds 2 and 3 showed potent inhibitory activity (IC50 35.6 μM, 80.8 μM, respectively) in the replicon cell assay, which was confirmed by NS3 helicase inhibitory activity (IC50 42.9 μM, 27.0 μM, respectively).

References

  • 1 Hepatitis C-global prevalence (update). Weekly Epidemiological Record. WHO 1999 74: 421-8.
  • 2 Zein C O, Zein N N. Advances in therapy for hepatitis C infection.  Microbes Infect. 2002;  4 1237-46.
  • 3 Nomura T, Fukai T, Yamada S, Katayanagi M. Studies on the constituents of the cultivated mulberry tree. I. Three new prenylflavones from the root bark of Morus alba L.  Chem Pharm Bull. 1978;  26 1394-402.
  • 4 Dai S J, Wu Y, Wang Y H, He W Y, Chen R Y, Yu D Q. New Diels-Alder type adducts from Morus macroura and their anti-oxidant activities.  Chem Pharm Bull. 2004;  52 1190-3.
  • 5 Basnet P, Kadota S, Terashima S, Shimizu M, Namba T. Two new 2-arylbenzofuran derivatives from hypoglycemic activity-bearing fractions of Morus insignis .  Chem Pharm Bull. 1993;  41 1238-43.
  • 6 Takasugi M, Nagao S, Masamune T. Structures of moracins E, F, G, and H, new phytoalexins from the diseased mulberry. Tetrahedron Lett 1979: 4675-8.
  • 7 Du J, He Z D, Jiang R W, Ye W C, Xu H X, But P P-H. Antiviral flavonoids from the root bark of Morus alba L.  Phytochemistry. 2003;  62 1235-8.
  • 8 Ukrainets I V, Taran E A, Gorokhova O V, Jaradat N A, Voronina L N, Porokhnyak I V. et al . Synthesis and biological activity of 1-R-2-oxo-3-(2H-1,2,4-benzothiadiazine-1,1-dioxid-3-yl)-4-hydroxyquinolines.  Chem Heterocylic Comp. 2000;  36 346-50.
  • 9 Gu B, Johnston V K, Gutshall L L, Nguyen T T, Gontarek R R, Darcy M G. et al . Arresting inhibition of hepatitis C virus RNA synthesis using heterocyclic Derivatived.  J Biol Chem. 2003;  278 16 602-7.
  • 10 Hirakura K, Fukimoto Y, Fukai T, Nomura T. Two phenolic glycosides from the root bark of the cultivated mulberry tree (Morus lhou).  J Nat Prod. 1986;  49 218-24.
  • 11 Dictionary of Natural Products. Vol. 9 (2nd supplement) Cambridge; University Press 1996: 246-7.
  • 12 Rollinger J M, Bodensieck A, Seger C, Ellmerer E P, Bauer R, Langer T. et al . Discovering COX-inhibiting constituents of Morus root bark: activity-guided versus computer-aided methods.  Planta Med. 2005;  71 399-405.
  • 13 Hano Y, Suzuki S, Nomura T, Ueda S. Two new phenolic compounds, kuwanols C and D, from the root bark of a mulberry tree redifferentiated from the callus tissues.  Heterocycles. 1989;  9 807-13.
  • 14 Su B N, Cuendet M, Hawthorne M E, Kardono L B, Riswan S, Fong H HS. et al . Constituents of the bark and twigs of Artocarpus dadah with cyclooxygenase inhibitory activity.  J Nat Prod. 2002;  65 163-9.
  • 15 Hano Y, Kohno H, Itoh M, Nomura T. Structures of three new 2-arylbenzofuran derivatives from the Chinese crude drug ”Sang-Bai-Pi” (Morus root bark).  Chem Pharm Bull. 1980;  33 5294-300.
  • 16 Borowski P, Deinert J, Schalinski S, Bretner M, Ginalski K, Kulikowski T. et al . Halogenated benzimidazoles and benzotriazoles as inhibitors of the NTPase/helicase activities of hepatitis C and related viruses.  Eur J Biochem. 2003;  270 1645-53.

1 These authors coordinated equally with this paper

Moon Jeong Leem, PhD

Natural Product Lab, R&D Center

Dong-Wha Pharmaceutical Ind. Co., Ltd.

189 Anyang 7-Dong

Anyang City

Kyonggi-Do

Korea

Phone: +82-31-445-2485

Fax: +82-31-446-9556

Email: natl@iris.dwcrc.co.kr

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