Dieugenol

Crystal structure of De-hydro-dieugenol B methyl ether, a neolignan from Nectandra leucantha Nees and Mart (Lauraceae).[Pubmed:29765758]

Acta Crystallogr E Crystallogr Commun. 2018 Mar 9;74(Pt 4):518-521.

In the title compound, C(21)H(24)O(4) (systematic name: 4,5'-diallyl-2,2',3'-tri-meth-oxy-diphenyl ether), the aromatic rings lie almost perpendicular to each other [dihedral angle = 85.96 (2) degrees ]. The allyl side chains show similar configurations, with C(ar)-C-C=C (ar = aromatic) torsion angles of -123.62 (12) and -115.54 (12) degrees . A possible weak intra-molecular C-Hcdots, three dots, centeredO inter-action is observed. In the crystal, mol-ecules are connected by two C-Hcdots, three dots, centeredO hydrogen bonds, forming undulating layers lying parallel to the bc plane. Weak C-Hcdots, three dots, centeredpi and pi-pi stacking inter-actions also occur.

Computer-aided discovery, validation, and mechanistic characterization of novel neolignan activators of peroxisome proliferator-activated receptor gamma.[Pubmed:20064974]

Mol Pharmacol. 2010 Apr;77(4):559-66.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists are used for the treatment of type 2 diabetes and metabolic syndrome. However, the currently used PPAR gamma agonists display serious side effects, which has led to a great interest in the discovery of novel ligands with favorable properties. The aim of our study was to identify new PPARgamma agonists by a PPAR gamma pharmacophore-based virtual screening of 3D natural product libraries. This in silico approach led to the identification of several neolignans predicted to bind the receptor ligand binding domain (LBD). To confirm this prediction, the neolignans Dieugenol, tetrahydroDieugenol, and magnolol were isolated from the respective natural source or synthesized and subsequently tested for PPAR gamma receptor binding. The neolignans bound to the PPAR gamma LBD with EC(50) values in the nanomolar range, exhibiting a binding pattern highly similar to the clinically used agonist pioglitazone. In intact cells, Dieugenol and tetrahydroDieugenol selectively activated human PPAR gamma-mediated, but not human PPAR alpha- or -beta/delta-mediated luciferase reporter expression, with a pattern suggesting partial PPAR gamma agonism. The coactivator recruitment study also demonstrated partial agonism of the tested neolignans. Dieugenol, tetrahydroDieugenol, and magnolol but not the structurally related eugenol induced 3T3-L1 preadipocyte differentiation, confirming effectiveness in a cell model with endogenous PPAR gamma expression. In conclusion, we identified neolignans as novel ligands for PPAR gamma, which exhibited interesting activation profiles, recommending them as potential pharmaceutical leads or dietary supplements.

Antioxidant activity of eugenol and related monomeric and dimeric compounds.[Pubmed:11045452]

Chem Pharm Bull (Tokyo). 2000 Oct;48(10):1467-9.

Since the inhibitory effect of eugenol (a), which was isolated as an antioxidative component from plant, Caryopylli flos, on lipid peroxidation was less than that of alpha-tocopherol, we synthesized the eugenol-related compounds Dieugenol (b), tetrahydroDieugenol (c), and dihydroeugenol (d), to find new strong antioxidants and assessed them for their inhibitory effect on lipid peroxidation and scavenging ability for superoxide and hydroxyl radicals. The antioxidative activities were in the order: (b)>(c)>(d)>(a) for the thiobarbituric acid reactive substance (TBARS) formation. These results suggest that the dimerized compounds have higher antioxidant activities than that of the monomers. Electron spin resonance (ESR) spin trapping experiments revealed that eugenol and its dimer, having allyl groups in the structure, scavenged superoxide, and that only eugenol trapped hydroxyl radicals under the conditions used. These finding suggest that eugenol and Dieugenol have a different mechanism of antioxidation, i.e. eugenol may inhibit lipid peroxidation at the level of initiation, however, the related dimeric compounds may inhibit lipid peroxidation at the level of propagation of free radical chain reaction like alpha-tocopherol.