Planta Med 2012; 78(12): 1357-1362
DOI: 10.1055/s-0032-1315001
Natural Product Chemistry
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Isoflavonoids from Ficus benjamina and Their Inhibitory Activity on BACE1

Jingqiu Dai
1   Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii, USA
,
Dai Shen
2   Kenyon College, Gambier, Ohio, USA
,
Wesley Y. Yoshida
1   Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii, USA
,
Stephen M. Parrish
1   Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii, USA
,
Philip G. Williams
1   Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii, USA
3   University of Hawaii Cancer Center, Honolulu, Hawaii, USA
› Author Affiliations
Further Information

Publication History

received 11 October 2011
revised 07 June 2012

accepted 08 June 2012

Publication Date:
04 July 2012 (online)

Abstract

Examination of an active extract of the fruit of Ficus benjamina var. nuda (Miq.) Barrett has led to the isolation of six new isoflavones and two coumarano-chroman-4-ones, along with fifteen known compounds. The structures of the eight new compounds were elucidated on the basis of extensive NMR experiments and mass spectrometric measurements. The inhibitory activity of the compounds on the proteolytic cleavage of amyloid precursor protein by the aspartic protease BACE1 was evaluated. Both coumarano-chroma-4-ones and some isoflavones showed moderate activity in this assay.

Supporting Information

 
  • References

  • 1 Kinghorn AD, Pan L, Fletcher JN, Chai H. The relevance of higher plants in lead compound discovery programs. J Nat Prod 2011; 74: 1539-1555
  • 2 Sirisha N, Sreenivasulu M, Sangeeta K, Madhusudhana C. Antioxidant properties of Ficus species – a review. Int J Pharmtech Res 2010; 2: 2174-2182
  • 3 Dai J, Sorribas A, Yoshida WY, Williams PG. Sebestenoids A–D, BACE1 inhibitors from Cordia sebestena . Phytochemistry 2010; 71: 2168-2173
  • 4 [Anonymous] Flora of North America. Available at: http://www.fna.org Accessed October 17, 2011
  • 5 Mousa O, Vuorela P, Kiviranta J, Wahab SA, Hiltunen R, Vuorela H. Bioactivity of certain Egyptian Ficus species. J Ethnopharmacol 1994; 41: 71-76
  • 6 Werfel S, Rüeff F, Przybilla B. Anaphylactic reaction to Ficus benjamina (weeping fig). Der Hautarzt 2001; 52: 935-937
  • 7 Parveen M, Ghalib RM, Mehdi SH, Rehman SZ, Ali M. A new triterpenoid from the leaves of Ficus benjamina (var. comosa). Nat Prod Res 2009; 23: 729-736
  • 8 Parveen M, Ghalib RM, Mehdi SH, Ul Hasan Mattu R, Ali M. A novel antimicrobial triterpenic acid from the leaves of Ficus benjamina (var. comosa). J Saudi Chem Soc 2009; 13: 287-290
  • 9 Simo CCF, Kouam SF, Poumale HMP, Simo IK, Ngadjui BT, Green IR, Krohn K. Benjaminamide: A new ceramide and other compounds from the twigs of Ficus benjamina (Moraceae). Biochem Syst Ecol 2008; 36: 238-243
  • 10 Deshpande V, Pendse ARP. Erythrinins A, B and C, three new isoflavones from the bark of Erythrina variegate . Indian J Chem B 1977; 15B: 205-207
  • 11 Naqvi T. Galactosidase enzyme fragment complementation as a high-throughput screening protease technology. J Biomol Screen 2004; 9: 398-408
  • 12 Stachel SJ, Coburn CA, Steele TG, Jones KG, Loutzenhiser EF, Gregro AR, Rajapakse HA, Lai MT, Crouthamel MC, Xu M, Tugusheva K, Lineberger JE, Pietrak BL, Espeseth AS, Shi XP, Chen-Dodson E, Holloway MK, Munshi S, Simon AJ, Kuo L, Vacca JP. Structure-based design of potent and selective cell-permeable inhibitors of human β-secretase (BACE-1). J Med Chem 2004; 47: 6447-6450
  • 13 Miyasea T, Sanoa M, Yoshinob KN. Antioxidants from Lespedeza homoloba (II). Phytochemistry 1999; 52: 311-319
  • 14 Fukai T, Nomura T. NMR spectra of isoprenoid substituted phenols. 4. Revised structures of albanins D and E, geranylated flavones from Morus alba . Heterocycles 1991; 32: 499-510
  • 15 Barm F, Aida M, Hano Y, Nomura T. Ficusins A and B, two new cyclic-monoterpene-substituted isoflavones from Ficus septic . Heterocycles 1995; 41: 2761-2768
  • 16 Ni G, Zhang QJ, Wang YH, Chen RY, Zheng ZF, Yu DQ. Chemical constituents of the stem bark of Morus cathayana . J Asian Nat Prod Res 2010; 12: 505-515
  • 17 Tahara S, Moriyama M, Orihara S, Ingham J, Kawabata J, Mizutani J. Naturally occurring coumaranochroman-4-ones: a new class of isoflavonoids from lupins and Jamaican dogwood. Z Naturforsch C 1991; 46?C: 331-340
  • 18 Matsumori N, Kaneno D, Murata M, Nakamura H, Tachibana K. Stereochemical determination of acyclic structures based on carbon-proton spin-coupling constants. A method of configurational analysis for natural products. J Org Chem 1999; 64: 866-876
  • 19 Rosselli S, Bruno M, Maggio A, Bellone G, Formisano C, Mattia C, Di Micco SGB. Two new flavonoids from Bonanna graeca: a DFT-NMR combined approach in solving structures. Eur J Org Chem 2007; 15: 2504-2510
  • 20 Hashidoko Y, Tahara S, Mizutani J. Isoflavonoids of yellow lupine. Part I. New complex isoflavones in the root of yellow lupine (Lupinus luteus L., cv. Barpine). Agric Biol Chem 1986; 50: 1797-1807
  • 21 Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H. Flavonols and flavones as BACE-1 inhibitors: structure-activity relationship in cell-free, cell-based and in silico studies reveal novel pharmacophore features. Biochim Biophys Acta 2008; 1780: 819-825
  • 22 Williams P, Sorribas A, Howes MJ. Natural products as a source of Alzheimerʼs drug leads. Nat Prod Rep 2011; 28: 48-77
  • 23 McGovern SL, Caselli E, Grigorieff N, Shoichet BK. A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J Med Chem 2002; 45: 1712-1722