Antispasmodic activity of pimaradienoic acid derivatives obtained by microbial transformation

Pimaradienoic acid (PA, 1) is a pimarane-type diterpene which is associated with a wide spectrum of biological activities, including its great ability to inhibit rat aorta contraction [1]. In the present work, the fungal transformation of PA (0.1g/L) was performed using culture of Aspergillus niger (1.5×10⁷ spores/mL) during 9 days of incubation. After this period, the culture was filtered and the aqueous layer was extracted with ethyl acetate to furnish the extract codified as AtPA. Chemical and NMR studies of AtPA allowed us to isolate and to identify four PA derivatives (2–5). The chemical structures of 2, 4 and 5 are described for the first time in the scientific literature.

In addition to the microbial transformation studies, inhibitory action of these diterpenes on phenylephrine-induced rat aorta contraction was performed [2]. Ours results show that these metabolites were not able to inhibit the rat aorta contractile response, thus suggesting that minor structural differences on PA chemical skeleton significantly influences its antispasmodic activity.