Biotransformation of ent-8(14),15-pimaradiene and antimicrobial activity of the obtained derivatives against multi-resistant Gram-positive bacteria

In the present work, the microbial transformation of ent-8(14),15-pimaradiene (Figure 1; 1; PI) 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]. PI was added as a dimethylsulfoxide solution (0.1g/L) and incubated for 7 days. The culture was filtered and the aqueous layer was extracted with ethyl acetate to furnish the extract codified as AoPI. Chemical and NMR studies of AoPI allowed us to isolate and to identify four PA derivatives (Figure 1: Compounds 2, 3, 4 and 5).

The antimicrobial activity of these metabolites was evaluated against a panel of 14 multi-resistant Gram-positive bacteria. For this purpose, the broth microdilution method was applied and the minimal inhibitory concentration (MIC) values were determined [2]. Diterpene 2 displayed significant inhibitory effect on the growth of these pathogens, showing MIC values very promising [3].

Figure 1: Chemical structures of PI (1) and its derivatives obtained through fermentation for 7 days with A. ochraceus.

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

References: 1. Bastos DZL et al. (2007) Phytochemistry 68: 834–839. 2. Porto TS et al. (2009) Molecules 14: 191–199. 3. Gibbons S (2008) Planta Med 74: 594–599.