New acyclic bis phenylpropanoid and neolignans, from Myristica fragrans Houtt., exhibiting PARP-1 and NF-κB inhibitory effects.

Abstract The bioassay-guided fractionation of the aril of Myristica fragrans (mace spice) yielded five phenolic compounds, one new acyclic bis phenylpropanoid ( 1 ) and four previously known phenolic compounds: compounds ( 1 ) ( S ) 1-(3,4,5-trimethoxyphenyl)-2-(3-methoxy-5-(prop-1-yl) phenyl)-propan-1-ol, ( 2 ) benzenemethanol; α-[1-[2,6-dimethoxy-4-(2-propen-1-yl)phenoxy]ethyl]-3,4-dimethoxy-1-acetate, ( 3 ) odoratisol A, phenol, 4-[(2 S ,3 S )-2,3-dihydro-7-methoxy-3-methyl-5-(1 E )-1-propenyl-2-benzofuranyl]-2,6-dimethoxy, ( 4 ) 1,3-benzodioxate-5-methanol,α-[1-[2,6-dimethoxy-4-(2-propenyl)phenoxy]ethyl]-acetate, ( 5 ) licarin C; benzofuran,2,3-dihydro-7-methoxy-3-methyl-5-(1 E )-1-yl-2-(3,4,5-trimethoxyphenyl). An NMR tube Mosher ester reaction was used in an approach to characterize and determine the assignment of the absolute configuration of the new isolated chiral alcohol ( 1 ). The PARP-1 inhibitory activity was evaluated for compound ( 1 ) (IC 50  = 3.04 μM), compound ( 2 ) (IC 50  = 0.001 μM), compound ( 4 ) (IC 50  = 22.07 μM) and compound ( 5 ) (IC 50  = 3.11 μM). Furthermore, the isolated secondary metabolites were tested for NF-κB and K-Ras inhibitory activities. When tested in the p65 assay, compounds ( 2 ) and ( 4 ) displayed potent NF-κB inhibition (IC 50  = 1.5 nM and 3.4 nM, respectively).