Biologically active saponins from Apodytes dimidiata

In previous studies Apodytes dimidiata E.Mey. ex Arn. (Icacinaceae) displayed activity against leishmaniasis [1]. Therefore, a bioassay guided isolation was performed in order to isolate the active constituents. Six saponins, never isolated from nature before, were identified by LC-MS/MS, GC-MS and 1D and 2D NMR: apodytine A (compound 1), apodytine B (compound 2), apodytine C (compound 3), apodytine D (compound 4), apodytine E (compound 5), apodytine F (compound 6).

Compounds 1, 2 and 3, having an acetyl group at the same position in the aglycon part of the molecule, were more active against Leishmania infantum (IC₅₀ values <1µM) and cytotoxic against MRC-5 cells (CC₅₀ values <10µM) than compounds 4, 5 and 6 (IC₅₀ <10 and CC₅₀ <20µM, respectively), which contain a hydroxyl functionality at the same position. These compounds, responsible at least in part for the antileishmanial activity of the plant, also showed a haemolytic activity, and antiangiogenic activity in the rat aorta ring assay. The latter might be due to a non-selective toxicity. Since saponins are known for their molluscicidal activity, the presence of these compounds might explain the use of Apodytes dimidiata against the snails Bulinus africanus and Biomphalaria pfeifferi, intermediate host snails of Schistosoma spp. [2].

Figure 1: Compound 1–6 (Apodytine A – F)

Compound	R1	R2	R3	R4	R5
1	isopentanoyl	acetyl	CHO	H	galactosyl
2	isopentanoyl	acetyl	CHO	H	arabinosyl
3	isopentanoyl	acetyl	CH3	H	galactosyl
4	isopentanoyl	H	CHO	acetyl	galactosyl
5	isopentanoyl	H	CHO	acetyl	galactosyl
6	isopentanoyl	H	CH3	acetyl	galactosyl

References: 1. Maes L. (2003) PhD Thesis: Lead identification and development of a new anti-leishmanial saponin PX-6518, isolated from the Vietnamses plant Maesa balansae, University of Antwerp, Antwerp.

2. Pretorius SJ et al. (1991)J Trop Med Hyg 94: 159–165.