Download PDF
Planta Med 2014; 80(01): 86-89
DOI: 10.1055/s-0033-1351102
Biological and Pharmacological Activity
Letters
Georg Thieme Verlag KG Stuttgart · New York

Antitrypanosomal Isothiocyanate and Thiocarbamate Glycosides from Moringa peregrina

Mahdi Ayyari
1   Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran
,
Peyman Salehi
1   Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran
,
Samad Nejad Ebrahimi
1   Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran
2   Department of Pharmaceutical Sciences, Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland
,
Stefanie Zimmermann
2   Department of Pharmaceutical Sciences, Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland
3   Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
,
Lena Portmann
2   Department of Pharmaceutical Sciences, Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland
,
R. Luise Krauth-Siegel
4   Center of Biochemistry, Heidelberg University, Heidelberg, Germany
,
Marcel Kaiser
3   Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
5   University of Basel, Basel, Switzerland
,
Reto Brun
3   Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
5   University of Basel, Basel, Switzerland
,
Hassan Rezadoost
1   Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran
,
Shamsali Rezazadeh
6   Department of Pharmacognosy and Phytochemistry, Institute of Medicinal Plants, ACECR, Karaj, Iran
,
Matthias Hamburger
2   Department of Pharmaceutical Sciences, Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland
› Author Affiliations
Further Information

Publication History

received 29 August 2013
revised 24 October 2013

accepted 28 October 2013

Publication Date:
05 December 2013 (online)

Also available at
    Permissions and Reprints

Abstract

O-Methyl (1), O-ethyl (2), and O-butyl (3) 4-[(α-L-rhamnosyloxy) benzyl] thiocarbamate (E), along with 4-(α-L-rhamnosyloxy) benzyl isothiocyanate (4) have been isolated from the aerial parts of Moringa peregrina. The compounds were tested for in vitro activity against Trypanosoma brucei rhodesiense and cytotoxicity in rat skeletal myoblasts (L6 cells). The most potent compound was 4 with an IC50 of 0.10 µM against T. b. rhodesiense and a selectivity index of 73, while the thiocarbamate glycosides 1, 2, and 3 showed only moderate activity. Intraperitoneal administration of 50 mg/kg body weight/day of 4 in the T. b. rhodesiense STIB 900 acute mouse model revealed significant in vivo toxicity. Administration of 10 mg/kg body weight/day resulted in a 95 % reduction of parasitemia on day 7 postinfection, but did not cure the animals. Because of its high in vitro activity and its ability to irreversibly inhibit trypanothione reductase, an attractive parasite-specific target enzyme, 4-[(α-L-rhamnosyloxy) benzyl] isothiocyanate (4), can be considered as a lead structure for the development and characterization of novel antitrypanosomal drugs.

Key words

isothiocyanate - Moringa peregrina - Moringaceae - Trypanosoma brucei rhodesiense - thiocarbamate glycoside

Supporting Information

 

  • References

  • 1 Brun R, Blum J, Chappuis F, Burri C. Human African trypanosomiasis. Lancet 2009; 375: 148-159
    PubMedGoogle Scholar
  • 2 Burri C, Brun R. Human African trypanosomiasis. In: Gordon CC, Zumla AI, editors Mansonʼs Tropical diseases. 22nd edition. Amsterdam: Saunders Elsevier; 2009: 1307-1325
    Google Scholar
  • 3 Dastan D, Salehi P, Reza Gohari A, Zimmermann S, Kaiser M, Hamburger M, Reza Khavasi H, Ebrahimi SN. Disesquiterpene and sesquiterpene coumarins from Ferula pseudalliacea, and determination of their absolute configurations. Phytochemistry 2012; 78: 170-178
    CrossrefPubMedGoogle Scholar
  • 4 Zimmermann S, Kaiser M, Brun R, Hamburger M, Adams M. Cynaropicrin: the first plant natural product with in vivo activity against Trypanosoma brucei . Planta Med 2012; 78: 553-556
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Adams M, Zimmermann S, Kaiser M, Brun R, Hamburger M. A protocol for HPLC-based activity profiling for natural products with activities against tropical parasites. Nat Prod Commum 2009; 4: 1377
    PubMedGoogle Scholar
  • 6 Mekonnen Y, Yardley V, Rock P, Croft S. In vitro antitrypanosomal activity of Moringa stenopetala leaves and roots. Phytother Res 1999; 13: 538-539
    CrossrefPubMedGoogle Scholar
  • 7 Elbatran SA, Abdel-Salam OM, Abdelshfeek KA, Nazif NM, Ismail SI, Hammouda FM. Phytochemical and pharmacological investigations on Moringa peregrina (Forssk) Fiori. Nat Prod Sci 2005; 11: 1-8
    PubMedGoogle Scholar
  • 8 Bennett RN, Mellon FA, Foidl N, Pratt JH, Dupont MS, Perkins L, Kroon PA. Profiling glucosinolates and phenolics in vegetative and reproductive tissues of the multi-purpose trees Moringa oleifera L. (horseradish tree) and Moringa stenopetala L. J Agric Food Chem 2003; 51: 3546-3553
    CrossrefPubMedGoogle Scholar
  • 9 Anwar F, Latif S, Ashraf M, Gilani AH. Moringa oleifera: a food plant with multiple medicinal uses. Phytother Res 2007; 21: 17-25
    CrossrefPubMedGoogle Scholar
  • 10 Fahey JW, Zalcmann AT, Talalay P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry 2001; 56: 5-51
    CrossrefPubMedGoogle Scholar
  • 11 Faizi S, Siddiqui BS, Saleem R, Siddiqui S, Aftab K. Isolation and structure elucidation of novel hypotensive agents, niazinin A, niazinin B, niazimicin and niaziminin A+ B from Moringa oleifera: the first naturally occurring thiocarbamates. J Chem Soc [Perkin I] 1992; 3237-3241
    PubMedGoogle Scholar
  • 12 Krauth-Siegel RL, Comini MA. Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochim Biophys Acta 2008; 1780: 1236-1248
    CrossrefPubMedGoogle Scholar
  • 13 Kjær A, Malver O, El-menshawi B, Reischt J. Isothiocyanates in myrosinase-treated seed extracts of Moringa peregrina . Phytochemistry 1979; 18: 1485-1487
    CrossrefPubMedGoogle Scholar
  • 14 Eilert U, Wolters B, Nahrstedt A. The antibiotic principle of seeds of Moringa oleifera and Moringa stenopetala . Planta Med 1981; 42: 55-61
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Shikita M, Fahey JW, Golden TR, Holtzclaw WD, Talalay P. An unusual case of ʼuncompetitive activationʼ by ascorbic acid: purification and kinetic properties of a myrosinase from Raphanus sativus seedlings. Biochem J 1999; 341: 725-732
    CrossrefPubMedGoogle Scholar
  • 16 Zhang Y, Talalay P. Mechanism of differential potencies of isothiocyanates as inducers of anticarcinogenic Phase 2 enzymes. Cancer Res 1998; 58: 4632-4639
    PubMedGoogle Scholar
  • 17 Mahéo K, Morel F, Langouët S, Kramer H, Le Ferrec E, Ketterer B, Guillouzo A. Inhibition of cytochromes P-450 and induction of glutathione S-transferases by sulforaphane in primary human and rat hepatocytes. Cancer Res 1997; 57: 3649-3652
    PubMedGoogle Scholar
  • 18 Saleem R, Meinwald J. Synthesis of novel hypotensive aromatic thiocarbamate glycosides. J Chem Soc [Perkin I] 2000; 391-394
    PubMedGoogle Scholar
  • 19 Faizi S, Siddiqui BS, Saleem R, Siddiqui S, Aftab K, Gilani AH. Novel hypotensive agents, niazimin A, niazimin B, Niazicin A and Niazicin B from Moringa oleifera: isolation of first naturally occurring carbamates. J Chem Soc [Perkin I] 1994; 3035-3040
    PubMedGoogle Scholar
  • 20 Leuck M, Kunz H. Synthesis of active principles from the leaves of Moringa oleifera using S-pent-4-enyl thioglycosides. Carbohydr Res 1998; 312: 33-44
    CrossrefPubMedGoogle Scholar
  • 21 Bauman RA. Cis-trans isomerism of thionocarbamate esters. J Org Chem 1967; 32: 4129-4132
    CrossrefPubMedGoogle Scholar
  • 22 Fueller F, Jehle B, Putzker K, Lewis JD, Krauth-Siegel RL. High throughput screening against the peroxidase cascade of African trypanosomes identifies antiparasitic compounds that inactivate tryparedoxin. J Biol Chem 2012; 287: 8792-8802
    CrossrefPubMedGoogle Scholar
  • 23 Nibret E, Wink M. Trypanocidal and antileukaemic effects of the essential oils of Hagenia abyssinica, Leonotis ocymifolia, Moringa stenopetala, and their main individual constituents. Phytomedicine 2010; 17: 911-920
    CrossrefPubMedGoogle Scholar
  • 24 Hannaert V. Sleeping sickness pathogen (Trypanosoma brucei) and natural products: therapeutic targets and screening systems. Planta Med 2011; 77: 586-597
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Schmidt TJ, Khalid SA, Romanha AJ, Alves TM, Biavatti MW, Brun R, Da Costa FB, de Castro SL, Ferreira VF, de Lacerda MV, Lago JH, Leon LL, Lopes NP, das Neves Amorim RC, Niehues M, Ogungbe IV, Pohlit AM, Scotti MT, Setzer WN, Soeiro MDNC, Steindel M, Tempone AG. The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases – part I. Curr Med Chem 2012; 19: 2128-2175
    PubMedGoogle Scholar
  • 26 Schmidt TJ, Khalid SA, Romanha AJ, Alves TM, Biavatti MW, Brun R, Da Costa FB, De Castro SL, Ferreira VF, De Lacerda MVG, Lago JHG, Leon LL, Lopes NP, Amorim RCDN, Niehues M, Ogungbe IV, Pohlit AM, Scotti MT, Setzer WN, Soeiro MDNC, Steindel M, Tempone AG. The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases – part II. Curr Med Chem 2012; 19: 2176-2228
    PubMedGoogle Scholar
  • 27 Jockers-Scherübl MC, Schirmer RH, Krauth-Siegel RL. Trypanothione reductase from Trypanosoma cruzi, catalytic properties of the enzyme and inhibition studies with trypanocidal compounds. Eur J Biochem 1989; 180: 267-272
    CrossrefPubMedGoogle Scholar