Neurotrophic effects of simplified mastigophorene analogs on mesencephalic dopaminergic cells in primary culture

Abstract

Mastigophorenes are dimeric isocuparane‐type sesquiterpenes of plant origin which have been found to exhibit neurotrophic properties. In this study, a simplified synthetically produced analog (1) and its dimethylether (2) were screened for potential neurotrophic effects on primary dopaminergic cell cultures in vitro. Dopaminergic cultures were prepared from embryonic mouse mesencephalon and 6‐day serum‐free cultures were exposed to low concentrations (0.05–5.0 μM) of these compounds for 6 days. Although differing by only two O‐methyl groups, the two substances differed in their effects on dopaminergic cells. 1 promoted growth of individual cells at low concentrations, whereas the more lipophilic 2 prevented cell death in culture and also clearly stimulated the growth of neuronal processes, although effects on growth of the total cell area were less pronounced. Effects on mitochondrial respiratory enzymes appear unlikely as 1 and 2 showed inhibitory effects only at concentrations 10–100‐fold higher than those used in cell culture. The results obtained show that synthetically produced substances analogous to neuron‐supportive mastigophorenes of plant origin can serve as neurotrophic substances. Drug Dev. Res. 50:153–156, 2000. © 2000 Wiley‐Liss, Inc.

Natural disesquiterpenoids

“…It is noteworthy that two simplified analogs of mastigophorene exerted similar neurotrophic effects on mesencephalic dopaminergic cells in primary culture, showing that the diphenyl core may be a key functional group for the retention of its bioactivity, and providing simplified lead compounds for further investigation. 209 The remarkable neurotrophic activity of these dimers has considerable attention from synthetic chemists. Several synthetic groups have accomplished the total synthesis of these dimers and their corresponding precursor, herbertenediol.…”

Nondynamic and Dynamic Kinetic Resolution of Lactones with Stereogenic Centers and Axes: Stereoselective Total Synthesis of Herbertenediol and Mastigophorenes A and B

“…Therefore the total synthesis of ( P ) - 1 and ( M ) - 1 is an attractive target, even more so because the interesting, C 2 -symmetric structures involve elements of both axial and centro chirality. In our investigations, we published two different strategies for the construction of the simplified analog 2 , the first one by a (nonstereoselective) biomimetic oxidative phenolic coupling, leading to the likewise neurotrophic mastigophorene analog 2 , and the second one using our “lactone methodology” for the atropo-enantioselective construction of the biaryl axis. An application of the biomimetic strategy to a simple derivative of the authentic monomeric half, 3 , led to the first formal total synthesis of ( P )- 1 and ( M )- 1 , albeit with moderate asymmetric inductions .…”

From Dynamic to Non-Dynamic Kinetic Resolution of Lactone-Bridged Biaryls: Synthesis of Mastigophorene B

“…Previous studies had shown that, like the mastigophorenes 6 themselves, 11 this model compound also has neurotrophic properties. 39 Starting from the known 28 This lactone-bridged biaryl 22 was found to be configurationally stable at room temperature by HPLC on a chiral stationary phase (Chiralcel OF, Daicel Chem. Ind.).…”