Planta Med 2011; 77 - PL55
DOI: 10.1055/s-0031-1282704

New vobasinyl-iboga bisindole alkaloids with antiparasitic activities from Muntafara sessilifolia

M Girardot 1, C Deregnaucourt 1, A Deville 1, L Dubost 1, R Joyeau 1, L Allorge 1, P Rasoanaivo 2, L Mambu 1
  • 1UMR 7245 CNRS-MNHN Communication Molecules and Adaptation of Micro-organisms, National Museum of Natural History. Box 54, 57 rue Cuvier, 75005 Paris, France.
  • 2Laboratory of Pharmacognosy applied to infectious diseases, Malagasy Institute of Applied Research. PO Box 3833, 101 Antananarivo, Madagascar.

Muntafara sessilifolia (Baker) Pichon or Tabernaemontana sessilifolia is an endemic plant of Madagascar which belongs to the Apocynaceae family. The stem-bark is traditionally used for the treatment of fevers and as tonic. Screening based on inhibitory activity against the chloroquine-resistant strain FcB1 of Plasmodium falciparum allowed the selection of this plant for a phytochemical investigation.

Selective acid-base extraction with gradient of pH performed on methanol extract from the powdered stem-bark, yielded a crude alkaloid and EtOAc extracts. Both extracts were active in vitro on P. falciparum with an IC 50 value of 1.6 and 6.5µg/ml, respectively. The bioassay-guided fractionation of EtOAc extract by combined chromatographic methods (preparative TLC, CC (SiO2, Al2O3), Sephadex ®LH 20 gel, MPLC, preparative HPLC) led to isolation of indole along with vobasinyl-iboga bisindole alkaloids as active constituents. Their structures were elucidated by spectrometric techniques (IR, UV, ESI-MS, 1D and 2D NMR (COSY, HSQC, HMBC, NOESY)). Six compounds are new among the thirteen isolated1, 2. NMR spectra at low temperature allowed the characterization of bisindole alkaloids whose 1H NMR spectra were not resolved at room temperature. A hypothesis of biogenesis is proposed.The antiparasitic on Plasmodium falciparum, Trypanosoma brucei brucei and Leishmania donovani and cytotoxic activities were evaluated on all obtained molecules. The selectivity towards parasites was determined. The attempt for the access to the target of active molecules on Plasmodium falciparum is discussed.

Figure 1: bisindole alkaloids from Muntafara sessilifolia

Acknowledgement: the MENESR

References: 1 Garnier et al. (1984)J Nat Prod 47(6): 1055–1056

2 Le Men et al. (1975) Phytochemistry 14: 1120–1122