Planta Med 2015; 81 - PX15
DOI: 10.1055/s-0035-1556459

A phenylpropanoid and neolignans from Myristica fragrans Houtt with PARP-1 and NF-κB inhibitory activity

U Muñoz Acuña 1, 2, PJ Blanco Carcache 1, 2, S Matthew 1, 2, EJ Carcache de Blanco 1, 2
  • 1Division of Pharmacy Practice and Administration
  • 2Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 141N Parks Hall 500 W. 12th Avenue, Columbus, OH 43210.

Bioassay guided fractionation of the aril of M. fragrans yielded five phenolic compounds, one new acyclic bis phenylpropanoid (1) and four previously known neolignans. Compound (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-[(2S, 3S)-2,3-dihydro-7-methoxy-3-methyl-5-(1E)-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-(1E)-1-yl-2-(3,4,5-trimethoxyphenyl). A NMR tube Mosher ester reaction was used to determine the absolute configuration of the new isolated chiral alcohol (1). PARP-1 inhibitory activity was evaluated for compound (1) (IC50 = 3.04µM), compound (2) (IC50 = 0.001µM), compound (4) (IC50 = 22.07µM) and compound (5) (IC50 = 3.11µM). All isolated secondary metabolites were also tested for NF-κB (p65) and K-Ras inhibitory activity. Compounds (2) and (4) displayed potent NF-κB inhibition, IC50 = 1.5 nM and 3.4 nM, respectively.