Antiprotozoal Isoflavan Quinones from Abrus precatorius ssp.
                        africanus

Yoshie Hata; Melanie Raith; Samad Nejad Ebrahimi; Stefanie Zimmermann; Tsholofelo Mokoka; Dashnie Naidoo; Gerda Fouche; Vinesh Maharaj; Marcel Kaiser; Reto Brun; Matthias Hamburger

doi:10.1055/s-0032-1328298

Planta Medica, Table of Contents

Planta Med 2013; 79(06): 492-498
DOI: 10.1055/s-0032-1328298

Natural Product Chemistry

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Antiprotozoal Isoflavan Quinones from Abrus precatorius ssp. africanus

Yoshie Hata

¹Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

⁴Departament of Pharmacy, Faculty of Sciences, National University of Colombia, Bogota D. C., Colombia

,

Melanie Raith

¹Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

,

Samad Nejad Ebrahimi

¹Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

⁵Department of Phytochemistry, Medicinal Plant and Drugs Research Institute, Shahid Beheshti University, G. C., Tehran, Iran

,

Stefanie Zimmermann

¹Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

²Swiss Tropical and Public Health Institute and University of Basel, Basel, Switzerland

,

Tsholofelo Mokoka

³Biosciences, Council for Scientific and Industrial Research (CSIR), Pretoria, South Africa

,

Dashnie Naidoo

³Biosciences, Council for Scientific and Industrial Research (CSIR), Pretoria, South Africa

,

Gerda Fouche

³Biosciences, Council for Scientific and Industrial Research (CSIR), Pretoria, South Africa

,

Vinesh Maharaj

³Biosciences, Council for Scientific and Industrial Research (CSIR), Pretoria, South Africa

,

Marcel Kaiser

²Swiss Tropical and Public Health Institute and University of Basel, Basel, Switzerland

,

Reto Brun

²Swiss Tropical and Public Health Institute and University of Basel, Basel, Switzerland

,

Matthias Hamburger

¹Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

› Author Affiliations

Abstract

A library of 206 extracts from selected South African plants was screened in vitro against a panel of protozoan parasites, Plasmodium falciparum, Trypanosoma brucei rhodesiense, and Leishmania donovani. A CH₂Cl₂/MeOH (1 : 1) extract of Abrus precatorius L. ssp. africanus strongly inhibited P. falciparum (98 %), T. b. rhodesiense (100 %), and L. donovani (76 %) when tested at a concentration of 10.0 µg/mL. The active constituents were tracked by HPLC-based activity profiling and isolated by preparative and semipreparative RP-HPLC chromatography. Structures were established by HR-ESIMS, and 1D and 2D NMR (¹H, ¹³C, COSY, HMBC, HSQC, and NOE difference spectroscopy). Five compounds were obtained and identified as two isoflavan hydroquinones, abruquinone H (1) and abruquinone G (2), and three isoflavan quinones, abruquinone I (3), abruquinone B (4), and 7,8,3′‚5′-tetramethoxyisoflavan-1′,4′-quinone (5). Compounds 1 and 3 were new natural products. The absolute configuration of compounds was determined by comparison of electronic circular dichroism spectra with calculated ECD data. Compounds 3 and 4 showed strong activity against T. b. rhodesiense (IC₅₀ values of 0.30 and 0.16 µM, respectively) and good selectivity (selectivity indices of 73.7 and 50.5, respectively).

Key words

antiprotozoal - Trypanosoma brucei rhodesiense - isoflavan quinone - Abrus precatorius - Fabaceae - electronic circular dichroism

Full Text

References

References
1 World Health Organization (WHO). Working to overcome the global impact of neglected tropical diseases: First WHO report on neglected tropical diseases. Geneva: WHO; 2010. (iii). 3, 14, 75, 82–84, 91–92
2 World Health Organization (WHO). Global malaria report. Geneva: WHO; 2011: 1
3 World Health Organization (WHO). The global burden of diseases: 2004 update. Geneva: WHO; 2008: 60
4 Rensol AR, McKerrow JH. Drug discovery and development for neglected diseases. Nat Chem Biol 2006; 2: 701-710
5 Hannaert V. Sleeping sickness pathogen (Trypanosoma brucei) and natural products: therapeutic targets and screening systems. Planta Med 2011; 77: 586-597
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 diseases. Nat Prod Commun 2009; 4: 1377-1381
7 Mokoka TA, Zimmermann 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
8 Zimmermann S, Kaiser M, Brun R, Hamburger M, Adams M. Cynaropicrin: the first natural product with in vivo activity against Trypanosoma brucei rhodesiense . Planta Med 2012; 78: 553-556
9 Hata Y, Zimmermann S, Quitschau M, Kaiser M, Brun R, Hamburger M, Adams M. Antiplasmodial and antitrypanosomal activity of pyrethrins and pyrethroids. J Agric Food Chem 2011; 59: 9172-9176
10 Olsnes S. The history of ricin, abrin and related toxins. Toxicon 2004; 44: 361-370
11 Lupi A, Monache FD, Marini-Bettolo GB. Abruquinones: new natural isoflavanquinones. Gazz Chim Ital 1979; 109: 9-12
12 Ma C, Nakamura N, Hattori M. Saponins and C-glycosyl flavones from the seeds of Abrus precatorius . Chem Pharm Bull 1998; 46: 982-987
13 Kuo SC, Chen SC, Chen LH, Wu JB, Wang JP, Teng CM. Potent antiplatelet, anti-inflammatory and antiallergic isoflavanquiones from the roots of Abrus precatorius . Planta Med 1995; 61: 307-312
14 Gathirwa JW, Rukunga GM, Mwitari PG, Mwikwabe NM, Kimani CW, Muthaura CN, Kiboi DM, Nyangacha RM, Omar SA. Traditional herbal antimalarial therapy in Kilifi district, Kenya. J Ethnopharmacol 2011; 134: 434-442
15 Ménan H, Banzouzi JT, Hocquette A, Pélissier Y, Blache Y, Koné M, Mallié M, Assi LA, Valentin A. Antiplasmodial activity and cytotoxicity of plants used in West Africa traditional medicine for the treatment of malaria. J Ethnopharmacol 2006; 105: 131-136
16 Limmatvapirat C, Sirisopanaporn S, Kittakoop P. Antitubercular and antiplasmodial constituents of Abrus precatorus . Planta Med 2004; 70: 276-278
17 Choi YH, Hussain RA, Pezzuto JM, Kinghorn AD, Morton JF. Abrusosides A–D, four novel sweet-tasting triterpene glycosides from the leaves of Abrus precatorius . J Nat Prod 1989; 52: 1118-1127
18 Xiao ZH, Wang FZ, Sun AJ, Li CR, Huang CG, Zhang S. A new triterpenoid saponin from Abrus precatorius Linn. Molecules 2012; 17: 295-302
19 Ghosal S, Dutta SK. Alkaloids of Abrus precatorius . Phytochemistry; 1971; 10: 195-198
20 Bhardwaj DK, Bisht MS, Mehta CK. Flavonoids from Abrus precatorius . Phytochemistry 1980; 19: 2040-2041
21 Song CQ, Hu ZB. Abruquinone A, B, D, E, F, and G from the root of Abrus precatorius . Acta Bot Sin 1998; 40: 734-739
22 Potterat O, Hamburger M. Natural products in drug discovery – concepts and approaches for tracking bioactivity. Curr Org Chem 2006; 10: 899-920
23 Kurosawa K, Ollist WD, Redman BT, Sutherland IO, Alves HM, Gottlieb OR. Absolute configuration of isoflavans. Phytochemistry 1978; 17: 1423-1426
24 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ. Gaussian 09, Revision A02. Wallingford: Gaussian, Inc; 2009
25 Bruhn T, Hemberger Y, Schaumlöffel A, Bringmann G. SpecDis, Version 1.51. Würzburg: University of Würzburg; 2011
26 Kamnaing P, Fanso Free SNY, Nkengfack AE, Folefoc G, Forum ZT. An isoflavan-quinone and a flavonol from Millettia laurentii . Phytochemistry 1999; 51: 829-832
27 Slade D, Ferreira D, Marais JPJ. Circular dichroism, a powerful tool for the assessment of absolute configuration of flavonoids. Phytochemistry 2005; 66: 2177-2215
28 Gichuki C, Brun R. Animal models of CNS (second-stage) sleeping sickness. In: Zak O, Sande MA, editors Animal models of infection. Bath: Academic Press; 1999: 795-801

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