Novel NGF-potentiating diterpenoids from a Brazilian medicinal plant,Ptychopetalum olacoides

From the MeOH extract of Ptychopetalum olacoides, which is used in Brazilian folk medicine for the treatment of chronic degenerative conditions of the nervous system, four novel clerodane-type diterpenoids named 6α,7α-dihydroxyannonene (1), 7α,20-dihydroxyannonene (2), 7α-hydroxysolidagolactone I (3), and ptycho-6α,7α-diol (4) were isolated by bioassay-directed fractionation using NGF-differentiated PC12 cells. The structures of 1–4 were established by extensive NMR spectroscopic analyses and chemical conversion. Compounds 1 and 2 significantly enhanced NGF-mediated neurite outgrowth in PC12 cells at concentrations ranging from 0.1 to 50.0 μM for 1 and 0.1 to 30.0 μM for 2, whereas 3 and 4 had no morphological effect on NGF-mediated PC12 cells in the same concentration range. The structure–activity relationship of these compounds is also discussed.