Planta Med 2014; 80(07): 599-603
DOI: 10.1055/s-0034-1368349
Natural Product Chemistry
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Antiplasmodial and Antioxidant Isoquinoline Alkaloids from Dehaasia longipedicellata

Azeana Zahari
1   Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
,
Foo Kit Cheah
4   Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
,
Jamaludin Mohamad
2   Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
,
Syazreen Nadia Sulaiman
1   Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
,
Marc Litaudon
3   Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Gif-sur Yvette, France
,
Kok Hoong Leong
4   Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
,
Khalijah Awang
1   Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
› Author Affiliations
Further Information

Publication History

received 22 September 2013
revised 28 February 2014

accepted 03 March 2014

Publication Date:
10 April 2014 (online)

Abstract

The crude extract of the bark of Dehaasia longipedicellata exhibited antiplasmodial activity against the growth of Plasmodium falciparum K1 isolate (resistant strain). Phytochemical studies of the extract led to the isolation of six alkaloids: two morphinandienones, (+)-sebiferine (1) and (−)-milonine (2); two aporphines, (−)-boldine (3) and (−)-norboldine (4); one benzlyisoquinoline, (−)-reticuline (5); and one bisbenzylisoquinoline, (−)-O-O-dimethylgrisabine (6). Their structures were determined on the basis of 1D and 2D NMR, IR, UV, and LCMS spectroscopic techniques and upon comparison with literature values. Antiplasmodial activity was determined for all of the isolated compounds. They showed potent to moderate activity with IC50 values ranging from 0.031 to 30.40 µM. (−)-O-O-dimethylgrisabine (6) and (−)-milonine (2) were the two most potent compounds, with IC50 values of 0.031 and 0.097 µM, respectively, that were comparable to the standard, chloroquine (0.090 µM). The compounds were also assessed for their antioxidant activities with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (IC50 = 18.40–107.31 µg/mL), reducing power (27.40–87.40 %), and metal chelating (IC50 = 64.30 to 257.22 µg/mL) having good to low activity. (−)-O-O-dimethylgrisabine (6) exhibited a potent antioxidant activity of 44.3 % reducing power, while di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium and metal chelating activities had IC50 values of 18.38 and 64.30 µg/mL, respectively. Thus it may be considered as a good reductant with the ability to chelate metal and prevent pro-oxidant activity. In addition to the antiplasmodial and antioxidant activities, the isolated compounds were also tested for their cytotoxicity against a few cancer and normal cell lines. (−)-Norboldine (4) exhibited potent cytotoxicity towards pancreatic cancer cell line BxPC-3 with an IC50 value of 27.060 ± 1.037 µM, and all alkaloids showed no toxicity towards the normal pancreatic cell line (hTERT-HPNE).

 
  • References

  • 1 WHO. World malaria report 2012. Geneva: World Health Organization; 2012: xii-xiii
  • 2 Rajahram G, Barber B, William T, Menon J, Anstey N, Yeo T. Deaths due to Plasmodium knowlesi malaria in Sabah, Malaysia: association with reporting as Plasmodium malariae and delayed parenteral artesunate. Malar J 2012; 11: 284
  • 3 Gulcin I, Oktay M, Kufrevioglu OI, Aslan A. Determination of antioxidant activity of lichen Cetraria islandica (L) Ach. J Ethnopharmacol 2002; 79: 325-329
  • 4 Griffiths MJ, Ndungu F, Baird KL, Muller DP, Marsh K, Newton CR. Oxidative stress and erythrocyte damage in Kenyan children with severe Plasmodium falciparum malaria. Br J Haematol 2001; 113: 486-491
  • 5 Yenesew A, Akala HM, Twinomuhwezi H, Chepkirui C, Irungu BN, Eyase FL, Kamatenesi-Mugisha M, Kiremire BT, Johnson JD, Waters NC. The antiplasmodial and radical scavenging activities of flavonoids of Erythrina burttii . Acta Trop 2012; 123: 123-127
  • 6 Tchinda AT, Fuendjiep V, Sajjad A, Matchawe C, Wafo P, Khan S, Tane P, Choudhary MI. Bioactive compounds from the fruits of Zanthoxylum leprieurii . Pharmacologyonline 2009; 1: 406-415
  • 7 Mukhtar MR, Hadi AHA, Litaudon M, Awang K. Morphinandienone alkaloids from Dehaasia longipedicellata . Fitoterapia 2004; 75: 792-794
  • 8 Mukhtar MR, Martin M-T, Domansky M, Pais M, Hadi AHA, Awang K. Phoebegrandines A and B, proaporphine-tryptamine dimers, from Phoebe grandis . Phytochemistry 1997; 45: 1543-1546
  • 9 Mohamad K, Hirasawa Y, Lim CS, Awang K, Hadi AHA, Takeya K, Morita H. Ceramicine A and walsogyne A, novel limonoids from two species of Meliaceae. Tetrahedron Lett 2008; 49: 4276-4278
  • 10 Mohamad K, Hirasawa Y, Litaudon M, Awang K, Hadi AHA, Takeya K, Ekasari W, Widyawaruyanti A, Zaini NC, Morita H. Ceramicines B–D, new antiplasmodial limonoids from Chisocheton ceramicus . Bioorg Med Chem 2009; 17: 727-730
  • 11 Othman R, Ibrahim H, Mohd MA, Mustafa MR, Awang K. Bioassay-guided isolation of a vasorelaxant active compound from Kaempferia galanga L. Phytomedicine 2006; 13: 61-66
  • 12 Burkill IH. A dictionary of the economic products of the Malay peninsula. 1st. edition. London: Crown Agents for the Colonies; 1935: 76
  • 13 Hsuen K. Orders and families of Malayan seed plants. Kuala Lumpur, Malaysia: University of Malaya; 1969: 35-37
  • 14 Lu ST, Tsai IL, Leou SP. Studies on the alkaloids of Formosan lauraceous plants. Part 31. Alkaloids of Dehaasia triandra . Phytochemistry 1989; 28: 615-620
  • 15 Lee SS, Chen CK, Chen IS, Chen CH. Chemical constituents from Dehaasia triandra. 1. Three new alkaloids, isocorydione, norisocorydione, and dehatriphine, from the leaves. J Nat Prod 1996; 59: 55-58
  • 16 Lee SS, Chen CK, Chen CH. Chemical constituents from Dehaasia triandra. II. Five new alkaloids, secoxanthoplanine, dehydroisocorydione, 11,8′-O-bisisocorydine, (8,8′-R)- and (8,8′-S)-bisisocorydine, isolated from the leaves. Tetrahedron 1996; 52: 6561-6568
  • 17 Said IM, Latiff A, Partridge SJ, Phillipson JD. Alkaloids from Dehaasia incrassata . Planta Med 1991; 57: 389
  • 18 Shi X, Mao Y, Saffiotti U, Wang L, Rojanasakul Y, Leonard SS, Vallyathan V. Antioxidant activity ot tetrandrine and its inhibition of quartz-induced lipid peroxidation. J Toxicol Environ Health 1995; 46: 233-248
  • 19 Yang MH, Yoon KD, Chin YW, Park JH, Kim J. Phenolic compounds with radical scavenging and cyclooxygenase-2 (COX-2) inhibitory activities from Dioscorea opposita . Bioorg Med Chem 2009; 17: 2689-2694
  • 20 Greve B, Lehman LG, Lell B, Luckner D, Schmidt-Ott R, Kremsner PG. High oxygen radical production is associated with fast parasite clearance in children with Plasmodium falciparum malaria. J Infect Dis 1999; 179: 1584-1586
  • 21 Percario S, Moreira DR, Gomes BAQ, Ferreira MES, Goncalves ACM, Laurindo PSOC, Vilhena TC, Dolabela MF, Green MD. Oxidative stress in malaria. Int J Mol Sci 2012; 13: 16346-16372
  • 22 Ngouela S, Lenta BN, Noungoue DT, Ngoupayo J, Boyom FF, Tsamo E, Gut J, Rosenthal PJ, Connolly JD. Anti-plasmodial and antioxidant activities of constituents of the seed shells of Symphonia globulifera Linn f. Phytochemistry 2006; 67: 302-306
  • 23 Kremsner PG, Greve B, Lell B, Luckner D, Schmid D. Malarial anemia in African children associated with high oxygen-radical production. Lancet 2000; 355: 40-41
  • 24 Egan TJ, Combrinck JM, Egan J, Hearne GR, Marques HM, Ntenteni S, Sewell BT, Smith PJ, Taylor D, van Schalkwyk DA, Walden JC. Fate of haem iron in the malaria parasite Plasmodium falciparum . Biochem J 2002; 365: 343-347
  • 25 Pradines B, Ramiandrasoa F, Basco LK, Bricard L, Kunesch G, Le BJ. In vitro activities of novel catecholate siderophores against Plasmodium falciparum . Antimicrob Agents Chemother 1996; 40: 2094-2098
  • 26 Tirzitis G, Bartosz G. Determination of antiradical and antioxidant activity: basic principles and new insights. Acta Biochim Pol 2010; 57: 139-142
  • 27 Weinberg ED. Iron availability and infection. Biochim Biophys Acta 2009; 1790: 600-605
  • 28 Wilson ME, Britigan BE. Iron acquisition by parasitic protozoa. Parasitol Today 1998; 14: 348-353
  • 29 Mabeza GF, Loyevsky M, Gordeuk VR, Weiss G. Iron chelation therapy for malaria: a review. Pharmacol Ther 1999; 81: 53-75
  • 30 Pradines B, Rolain JM, Ramiandrasoa F, Fusai T, Mosnier J, Rogier C, Daries W, Baret E, Kunesch G, Le BJ, Parzy D. Iron chelators as antimalarial agents: in vitro activity of dicatecholate against Plasmodium falciparum . J Antimicrob Chemother 2002; 50: 177-187
  • 31 Trager W, Jensen JB. Human malaria parasites in continuous culture. Science 1976; 193: 673-675
  • 32 Lambros C, Vanderberg JP. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol 1979; 65: 418-420
  • 33 Noedl H, Bronnert J, Yingyuen K, Attlmayr B, Kollaritsch H, Fukuda M. Simple histidine-rich protein 2 double-site sandwich enzyme-linked immunosorbent assay for use in malaria drug sensitivity testing. Antimicrob Agents Chemother 2005; 49: 3575-3577
  • 34 Shimada K, Fujikawa K, Yahara K, Nakamura T. Antioxidative properties of xanthan on the autoxidation of soybean oil in cyclodextrin emulsion. J Agric Food Chem 1992; 40: 945-948
  • 35 Oyaizu M. Studies on product of browning reaction prepared from glucose amine. Jpn J Nutr 1986; 44: 307-315
  • 36 Dinis TCP, Madeira VMC, Almeida LM. Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Arch Biochem Biophys 1994; 315: 161-169