Lathyrane, Premyrsinane, and Related Diterpenes from Euphorbia boetica: Effect on in Vitro Neural Progenitor Cell Proliferation

Lathyrane-type diterpenes previously have been proven to promote proliferation of neural precursor cells (NPCs) by targeting and activating one or more protein kinase C (PKC) isozymes. Aiming to find new drug candidates with a lathyrane skeleton to modulate adult neurogenesis through PKC activation, a phytochemical study of a methanol extract of the aerial parts of Euphorbia boetica was carried out. Seven new diterpenes, representing the premyrsinane ( 1 - 3 ), myrsinane ( 4 , 5 ), and cyclomyrsinane types ( 6 , 7 ), along with three known diterpenes, belonging to the cyclomyrsinane ( 8 ) and lathyrane types ( 9 , 10 ), were isolated. The chemical structures and relative configurations of the new compounds were determined by extensive NMR spectroscopic studies and comparison with known compounds. The absolute configurations for compounds 2 , 3 , 6 , and 7 were proposed, based on a comparison of the experimental ECD spectra of compounds 2 and 7 with those of known related compounds. The activity of lathyrane compounds 9 and 10 as promoters of NPC proliferation was evaluated using a neurosphere assay. Both compounds increased the size of neurospheres in a dose-dependent manner when proliferation was stimulated by the epidermal growth factor and the basic fibroblast growth factor.