Antiplasmodial, Antitrypanosomal, and Cytotoxic Activities of Prenylated Flavonoids Isolated from the Stem Bark of Artocarpus styracifolius

 

 Buy Article Permissions and Reprints

Abstract

In continuation of our efforts to find new antimalarial drugs, a systematic in vitro evaluation using a chloroquine resistant strain of Plasmodium falciparum (FcB1) was undertaken on extracts prepared from various parts of Vietnamese plants. The ethyl acetate extract obtained from the stem bark of Artocarpus styracifolius (Moraceae) exhibited strong antiplasmodial activity (87 % at 10 µg/mL) whereas weak cytotoxicity was observed in a human fibroblast cell line (MRC-5). Phytochemical investigation of this extract led to isolation of two new prenylated flavonoids, styracifolins A and B (1 and 2), as well as the known artoheterophyllin A (3) and B (4), artonins A (5), B (6), and F (7), and heterophyllin (8). Structures of 1 and 2 were elucidated by spectroscopic methods and through comparison with data reported in the literature. Compounds 1–8 exhibited antiplasmodial activities with IC₅₀ values ranging from 1.1 µM to 13.7 µM, and compounds 1, 2, 6, and 8 showed significant antitrypanosomal activities.

References

• 1 Mabberley D J. The plant-book, 2nd edition. Cambridge; Cambridge University Press 1997: 58
  PubMedGoogle Scholar
• 2 Ho P H. Cay co Vietnam (An Illustrated Flora of Vietnam), Vol. II. Ho Chi Minh City; Nha xuat ban tre Youth Publishing House 2000: 548
  PubMedGoogle Scholar
• 3 Grosvenor P W, Gothard P K, McWilliam N, Supriono A, Gray D O. Medicinal plants from Riau Province, Sumatra, Indonesia. Part 1: uses.  J Ethnopharmacol. 1995;  45 75-95
  CrossrefPubMedGoogle Scholar
• 4 Sharma H K, Changte L, Dolui A K. Traditional medicinal plants in Mizoram, India.  Fitoterapia. 2001;  72 146-161
  CrossrefPubMedGoogle Scholar
• 5 Ajibesin K K, Ekpo B A, Bala D N, Essien E E, Adesanya S A. Ethnobotanical survey of Akwa Ibom State of Nigeria.  J Ethnopharmacol. 2008;  115 387-408
  CrossrefPubMedGoogle Scholar
• 6 Tene V, Malagon O, Finzi P V, Vidari G, Armijos C, Zaragoza T. An ethnobotanical survey of medicinal plants used in Loja and Zamora-Chinchipe, Ecuador.  J Ethnopharmacol. 2007;  111 63-81
  CrossrefPubMedGoogle Scholar
• 7 Boyom F F, Kemgne E M, Tepongning R, Ngouana V, Mbacham W F, Tsamo E, Zollo P H A, Gut J, Rosenthal P J. Antiplasmodial activity of extracts from seven medicinal plants used in malaria treatment in Cameroon.  J Ethnopharmacol. 2009;  123 483-488
  CrossrefPubMedGoogle Scholar
• 8 Boonlaksiri C, Oonanant W, Kongsaeree P, Kittakoop P, Tanticharoen M, Thebtaranonth Y. An antimalarial stilbene from Artocarpus integer.  Phytochemistry. 2000;  54 415-417
  CrossrefPubMedGoogle Scholar
• 9 Hakim E H, Yurnawilis A, Aimi N, Kitajima M, Takayama H. Artoindonesianin P, a new prenylated flavone with cytotoxic activity from Artocarpus lanceifolius.  Fitoterapia. 2002;  73 668-673
  CrossrefPubMedGoogle Scholar
• 10 Syah Y M, Achmad S A, Ghisalberti E L, Hakim E H, Mujahidin D. Two new cytotoxic isoprenylated flavones, artoindonesianins U and V, from the heartwood of Artocarpus champeden.  Fitoterapia. 2004;  75 134-140
  CrossrefPubMedGoogle Scholar
• 11 Aida M, Shinomiya K, Hano Y, Nomura T. Artonins J, K, and L, three new isoprenylated flavones from the root bark of Artocarpus heterophyllus Lamk.  Heterocycles. 1993;  36 575-582
  CrossrefPubMedGoogle Scholar
• 12 Wei B L, Weng J R, Chiu P H, Hung C F, Wang J P, Lin C N. Antiinflammatory flavonoids from Artocarpus heterophyllus and Artocarpus communis.  J Agric Food Chem. 2005;  53 3867-3871
  CrossrefPubMedGoogle Scholar
• 13 Weng J R, Chan S C, Lu Y H, Lin H C, Ko H H, Lin C H. Antiplatelet prenylflavonoids from Artocarpus communis.  Phytochemistry. 2006;  67 824-829
  CrossrefPubMedGoogle Scholar
• 14 Namdaung U, Aroonrerk N, Suksamrarn S, Danwisetkanjana K, Saenboonrueng J, Arjchomphu W, Suksamrarn A. Bioactive constituents of the root bark of Artocarpus rigidus subsp. igidus.  Chem Pharm Bull. 2006;  54 1433-1436
  CrossrefPubMedGoogle Scholar
• 15 Boonphong S, Baramee A, Kittakoop P, Puangsombat P. Antitubercular and antiplasmodial prenylated flavones from the roots of Artocarpus altilis.  Chiang Mai J Sci. 2007;  34 339-344
  PubMedGoogle Scholar
• 16 Widyawaruyanti A, Kalauni S K, Awale S, Nindatu M, Zaini N C, Syafruddin D, Asih P B S, Tezuka Y, Kadota S. New prenylated flavones from Artocarpus champeden, and their antimalarial activity in vitro.  J Nat Med. 2007;  61 410-413
  CrossrefPubMedGoogle Scholar
• 17 Fotie J. The antiprotozoan potential of flavonoids.  Pharmacognosy Rev. 2008;  2 6-19
  PubMedGoogle Scholar
• 18 Guillon J, Grellier P, Labaied M, Sonnet P, Leger J M, Deprez-Poulain R, Forfar-Bares I, Dallemagne P, Lemaitre N, Pehourcq F, Rochette J, Sergheraert C, Jarry C. Synthesis, antimalarial activity, and molecular modeling of new pyrrolo[1,2-a]quinoxalines, bispyrrolo[1,2-a]quinoxalines, bispyrido[3,2-e]pyrrolo[1,2-a]pyrazines, and bispyrrolo[1,2-a] thieno[3,2-e]pyrazines.  J Med Chem. 2004;  47 1997-2009
  CrossrefPubMedGoogle Scholar
• 19 Räz B, Iten M, Grether-Bühler Y, Kaminsky R, Brun R. The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T. b. rhodesiense and T. b. gambiense) in vitro.  Acta Trop. 1997;  68 139-147
  CrossrefPubMedGoogle Scholar
• 20 Tempête C, Werner G H, Favre F, Rojas A, Langlois N. In vitro cytostatic activity of 9-demethoxyporothramycin B.  Eur J Med Chem. 1995;  30 647-650
  CrossrefPubMedGoogle Scholar
• 21 Hano Y, Aida M, Shiina M, Nomura T, Kawai T, Ohe H, Kagei K. Artonins A and B, two new prenylflavones from the root bark of Artocarpus heterophyllus Lamk.  Heterocycles. 1989;  29 1447-1453
  CrossrefPubMedGoogle Scholar
• 22 Kijoa A, Cidada H M, Pinto M M M, Gonzalez M J T G, Anantachoke C, Gedris T E, Herz W. Prenylflavonoids from Artocarpus elasticus.  Phytochemistry. 1996;  43 691-694
  CrossrefPubMedGoogle Scholar
• 23 Hano Y, Yamagami Y, Kobayashi M, Isohata R, Nomura T. Artonins E and F, two new prenylflavones from the bark of Artocarpus communis Forst.  Heterocycles. 1990;  31 877-882
  CrossrefPubMedGoogle Scholar
• 24 Pearl I A, Darling S F. Hot-water extractives of the leaves of Populus heterophylla L.  J Agic Food Chem. 1977;  25 730-734
  CrossrefPubMedGoogle Scholar
• 25 Zheng Z P, Chen S, Wang S, Wang X C, Cheng K W, Wu J J, Yang D, Wang M. Chemical components and tyrosinase inhibitors from the twigs of Artocarpus heterophyllus.  J Agic Food Chem. 2009;  57 6649-6655
  CrossrefPubMedGoogle Scholar
• 26 Khaomek P, Ichino C, Ishiyama A, Sekiguchi H, Namatame M, Ruangrungsi N, Saifah E, Kiyohara H, Otoguro K, Omura S, Yamada H. In vitro antimalarial activity of prenylated flavonoids from Erythrina fusca.  J Nat Med. 2008;  62 217-220
  CrossrefPubMedGoogle Scholar
• 27 Tasdemir D, Kaiser M, Brun R, Yardley V, Schmidt T J, Tosun F, Ruedi P. Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure-activity relationship and quantitative structure-activity relationship studies.  Antimicrob Agents Chemother. 2006;  50 1352-1364
  CrossrefPubMedGoogle Scholar

Dr. Marc Litaudon

Institut de Chimie des Substances Naturelles

1 avenue de la Terrasse

91198 Gif-sur-Yvette

Cedex

France

Phone: + 33 1 69 82 30 85

Fax: + 33 1 69 07 72 47

Email: marc.litaudon@icsn.cnrs-gif.fr