Biotransformation of 1α,11α-dihydroxyisopimara-8(14),15-diene by Cunninghamella echinulata NRRL 1386 and their neuroprotective activity

Abstract

The isopimarane diterpene, 1α,11α-dihydroxyisopimara-8(14),15-diene (1), is the major constituents from the rhizomes of Kaempferia marginata (Zingiberaceae), a Thai medicinal plant. The microbial transformation of parent compound 1 by the fungus Cunninghamella echinulata NRRL 1386 gave five new metabolites, 7α,11α-dihydroxy-1-oxoisopimara-8(14),15-diene (2), 3β,7α,11α-trihydroxy-1-oxoisopimara-8(14),15-diene (3), 7β,11α-dihydroxy-1-oxoisopimara-8(14),15-diene (4), 7α-hydroxy-1,11-dioxoisopimara-8(14),15-diene (5) and 1α,7β,11α-trihydroxyisopimara-8(14),15-diene (6), together with three known metabolites, 7–9. The structures of the new metabolites were elucidated by spectroscopic techniques. The known compounds were identified by comparison of the spectroscopic and physical data with those of reported values. The parent compound 1 and the metabolites have been neuroprotective activities evaluated against Aβ25-35-induced damage in human neuroblastoma cells (SK-N-SH). Among them, compounds 1–3, 5 and 7–9 had significant neuroprotective activities at a concentration of 2.5 μM. The results demonstrated that these compounds might be worth for further development into therapeutic agents for the treatment of neurodegenerative diseases.