Planta Med 2011; 77 - PL84
DOI: 10.1055/s-0031-1282733

Fungal transformation of pimaradienoic acid and its schistosomicidal activity against Schistosoma mansoni

SR Ambrósio 1, TS Porto 1, AA Filho 1, LG Magalhães 1, RC Veneziani 1, NA Furtado 2, MR Simão 1, ME Severiano 1, ME Melo 1, V Rodrigues 2, S Said 2
  • 1University of Franca, Av. Dr. Armando Salles de Oliveira 201, 14404–600, Franca-SP, Brazil.
  • 2University of São Paulo, Av. Café s/n, 14040–903, Ribeirão Preto-SP, Brazil.

In the present work, the microbial transformation of pimaradienoic acid (PA, 1) (Figure 1) was performed using submerged shaken liquid culture of Aspergillus ochraceus (1.8×106 spores/mL). The microorganism was grown by a two-stage fermentation procedure [1]. PA was added as a dimethylsulfoxide solution (0.1g/L) and incubated for 3 days. The culture was filtered and the aqueous layer was extracted with ethyl acetate to furnish the extract codified as AoPA. Chemical and NMR studies of AoPA allowed us to isolate and to identify two PA derivatives (Figure 1: Compounds 2 and 3).

The in vitro schistosomicidal activity of these metabolites was performed against male and female S. mansoni adult worms [2], and the results denote that PA is very effective with respect to the separation of coupled pairs, mortality, decrease in the motor activity and tegumental alterations. In addition, PA is able to reduce the percentage of eggs number and eggs development. In this context, the schistosomicidal effects of PA indicate that ent-pimarane diterpenes could be considered a promising source for discovery of new agents to treat human schistosomiasis.

Figure 1: Chemical structures of PA (1) and its derivatives obtained through fermentation for 3 days with A. ochraceus.

Acknowledgement: FAPESP (Proc. 2007/54762–8)

References: 1. Bastos DZL et al. (2007) Phytochemistry 68: 834–839. 2. Magalhães LG et al. (2010) Parasitol Res 106: 395–401.