Dihydrophenanthrene derivatives (imbricatin and methoxycoelonin), bibenzyls (gigantol and batatasin III), and dihydroconiferyl dihydro-p-coumarate (DDPC) were isolated for the first time from the stems of a tropical orchid Aerides rosea (Figure 1). Imbricatin, methoxycoelonin and gigantol have been shown to display in vitro antioxidant and anti-inflammatory activities [1]. However, up to now, their redox reactivity was insufficiently characterized.
The in vitro antioxidant activity of the isolated compounds is described as their capacity i) to scavenge the DPPH● and ABTS+● free radicals and ii) to inhibit t-butyl hydroperoxide-induced lipid peroxidation (LPx). Quantum chemistry calculations (based on Density Functional Theory) were achieved to predict thermodynamic descriptors, mainly O-H bond dissociation enthalpies (BDEs). Molecular dynamics simulations were used to rationalize the differences in activity, in particular to predict the capacity of the compounds to insert lipid bilayers [2].
Imbricatin and methoxycoelonin exhibited relatively low BDE values, providing great free radical scavenging capacity. With relatively deep insertion inside lipid bilayer membranes, they allow efficient inhibition of the propagation stage of LPx. DDPC was confirmed to be an efficient free radical scavenger. However, it was less efficient as LPx inhibitor than the two dihydrophenanthrenes. This is possibly due to the negative charge and the pKa values which may partially prevent insertion into lipid bilayer. Despite exhibiting a relatively low O-H BDE value (so a relatively low IC50 in DPPH scavenging), gigantol was a less efficient LPx inhibitor than batatasin III. This was attributed to a deeper insertion inside lipid bilayer of the latter compared to the former derivative.
These new data allowed to establish clear structure-activity relationships in terms of free radical scavenging of studied compounds, also shedding light on their mechanisms of action.
[1] Simmler C. et al. (2010). Plos One 5(10):e13713.
[2] Anouar el H. et al. (2013). J Comput Aided Mol Des 27:951-64
