Antiprotozoal Screening of 60 South African Plants, and the Identification of the Antitrypanosomal Germacranolides Schkuhrin I and II

Abstract

Two hundred and seven extracts were prepared from sixty plants from South Africa and screened for in vitro activity against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum. For the 21 extracts which inhibited the growth of one or more parasites with more than 95 % at 10 µg/mL, the IC₅₀ values against all four protozoal parasites and cytotoxic IC₅₀ values against L6 myoblasts were determined. Amongst the most notable results are the activities of Psoralea pinnata (IC₅₀ of 0.15 µg/mL), Schkuhria pinnata (2.04 µg/mL), and Vernonia mespilifolia (1.01 µg/mL) against Trypansoma brucei rhodesiense. HPLC-based activity profiling was used to identify the active constituents in the extracts, and the germacranolide sesquiterpene lactones schkuhrin I and II from S. pinnata, and cynaropicrin from V. mespilifolia were identified, with IC₅₀ values of 0.9, 1.5, and 0.23 µM, respectively.

Key words

screening - plant extract library - antiprotozoal activity - sesquiterpene lactones - Trypansoma brucei rhodesiense - Trypanosoma cruzi - Leishmania donovani - Plasmodium falciparum - Psoralea pinnata (Fabaceae) - Schkuhria pinnata (Asteraceae) - Vernonia mespilifolia (Asteraceae)

• References

• 1 Hotez PJ, Molyneuz DH, Fenwick A, Kumaresan J, Sachs SE, Sachs JD, Savioloi L. Control of neglected tropical diseases. N Engl J Med 2007; 357: 1018-1027
• 2 Stuart K, Brun R, Croft S, Fairlamb A, Gürtler RE, McKerrow J, Reed S, Tarleton R. Kinetoplastids: related protozoan pathogens, different diseases. J Clin Invest 2008; 118: 1301-1310
• 3 World Health Organization. World malaria report 2011. Geneva: WHO; 2011: 1-278
• 4 Orhan I, Şener B, Kaiser M, Brun R, Tasdemir D. Inhibitory activity of marine sponge-derived natural products. Mar Drugs 2010; 8: 47-58
• 5 Mokoka TA, Zimmerman S, Julianti T, Hata Y, Moodley N, Cal M, Adams M, Kaiser M, Brun R, Koorbanally N, Hamburger M. In vitro screening of traditional South African malaria remedies against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum . Planta Med 2011; 77: 1663-1667
• 6 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 Commun 2009; 4: 1377-1381
• 7 Pettei MJ, Miura Y, Kubo Y, Nakanishi K. Insect antifeedant sesquiterpene lactones from Schkuhria pinnata: the direct obtention of pure compounds using reverse-phase preparative liquid chromatography. Heterocycles 1978; 11: 471-480
• 8 Yayli N, Baltaci C, Gök Y, Aydin E, Üçüncü O. Sesquiterpene lactones from Centaurea helenioides Boiss. Turk J Chem 2006; 30: 229-233
• 9 Watt JM, Breyer-Brandwijk MG. The medicinal and poisonous plants of Southern and Eastern Africa. 2nd. edition. London: E.&S. Livingstone Ltd.; 1962
• 10 Luseba D. The effects of extracts of some indigenous South African plants on in vitro cultures of Brucella abortus . Planta Med 2008; 74: PA336
• 11 León A, Reyes BM, Delgado G. Sesquiterpene lactones and other bioactive constituents from Schkuhria pinnata var. wislizeni (Asteraceae). Planta Med 2008; 74: 1034 (PB27)
• 12 Clarkson C, Maharaj VJ, Crouch NR, Grace OM, Pillay P, Matsabisa MG, Bhagwandin N, Smith PJ, Folb PI. In vitro antiplasmodial activity of medicinal plants native to or naturalised in South Africa. J Ethnopharmacol 2004; 92: 177-191
• 13 Hutchings A, Scott AH, Lewis G, Cunningham A. Zulu medicinal plants: an inventory. Pietermarizburg: Natal University Press; 1996
• 14 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, de N C Soeiro M, 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
• 15 http://www.mobot.org/MOBOT/research/APweb Accessed October 10, 2012.
• 16 Schmidt TJ, Nour AMM, Khalid SA, Kaiser M, Brun R. Quantitative structure-antiprotozoal activity relationships of sesquiterpene lactones. Molecules 2009; 14: 2062-2076
• 17 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
• 18 Zimmermann S, Oufir M, Leroux A, Krauth-Siegel RL, Becker K, Brun R, Hamburger M, Adams M. Cynaropicrin targets the trypanothione redox system in Trypanosoma brucei . Int J Parasitol Drugs Drug Resist 2013; submitted