Planta Med 2013; 79 - SL2
DOI: 10.1055/s-0033-1351828

Antiprotozoal isoflavan quinones from Abrus precatorius

Y Hata 1, M De Mieri 2, S Ebrahimi 3, S Zimmermann 2, R Melanie 2, D Naidoo 4, G Fouche 4, T Mokoka 4, V Maharaj 4, U Kaiser 5, R Brun 5, M Hamburger 2
  • 1University of Basel, Department of Pharmaceutical Biology, Basel (4056), Switzerland. National University of Colombia, Department of Pharmacy, Bogota (111321), Colombia
  • 2University of Basel, Department of Pharmaceutical Biology, Basel (4056), Switzerland
  • 3University of Basel, Department of Pharmaceutical Biology, Basel (4056), Switzerland.
  • 4Council for Scientific and Industrial Research, Biosciences, Pretoria (0002), South Africa
  • 5Swiss Tropical and Public Health Institute, Basel (4002), Switzerland

A library of 309 extracts from selected South African plants was screened in vitro against a panel of protozoan parasites. A CH2Cl2/MeOH (1:1) extract of the whole plant of Abrus precatorius L. ssp. africanus Verdc. (Fabaceae) inhibited Plasmodium falciparum (97.8%), Trypanosoma brucei rhodesiense (100%), and Leishmania donovani (75.5%) when tested at 4.8 mg/mL. Active constituents in two different batches of plant material were tracked by HPLC-based activity profiling, and isolated by normal phase flash chromatography and RP-HPLC. Structures and relative configuration of compounds were established by NMR (1H, 13C, COSY, HMBC, HSQC, NOE difference). The absolute configuration was determined by comparison of electronic circular dichroism (ECD) spectra with calculated ECD data. Ten compounds (Fig. 1) were obtained and identified as isoflavan quinones and hydroquinones, among them five new natural products. Abruquinone I (1) and abruquinone B (8) showed strong in vitro activity against T. brucei rhodesiense (IC50s of 0.30µM ± 0.1 and 0.16µM ± 0.1, respectively). Selectivity indices (SI) as calculated from cytotoxicity data in L-6 cells were 78.3 and 61.3. These SI qualify 1 and 8 as good candidates for assessment of in vivo activity. In contrast, compound 2 was not selective, even though very active (IC50 0.88µM ± 0.1; SI 4.5) [1]. Given that 1 and 8 possess a tenfold higher SI than cynaropicrin, the only plant derived compound with demonstrated in vivo activity against T. b. rhodesiense [2], 1 and 8 are of considerable interest.

Fig. 1

References:

[1] Hata Y, Raith M, Ebrahimi SN, Zimmermann S, Mokoka T, Naidoo D, Fouche G, Maharaj V, Kaiser M, Brun R, Hamburger M. Antiprotozoal isoflavan quinones from Abrus precatorius ssp. africanus. Planta Med, 2013, DOI: 10.1055/s-0032 – 1328298.

[2] 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.