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

• Published in: Food chemistry 2016-07, Vol.202, p.269-275
• Main Authors: Muñoz Acuña, Ulyana, Carcache, Peter J. Blanco, Matthew, Susan, Carcache de Blanco, Esperanza J.
• Format: Article
• Language: English
• Subjects: Acyclic bisphenyl propanoids; Biochemistry; Biokemi; Biomedical Sciences; Biomedicinsk vetenskap; Engelska med litteraturvetenskaplig inriktning; English literature; HT29 Cells; Humans; K-Ras; Lignans - isolation & purification; Lignans - pharmacology; Mace; Magnetic Resonance Spectroscopy; Medical Chemistry; Medicinsk kemi; Myristica fragrans; Myristica fragrans - chemistry; Neolignans; NF-kappa B - antagonists & inhibitors; NF-κB; Organic Chemistry; Organisk kemi; PARP-1; Phenols - isolation & purification; Phenols - pharmacology; Poly(ADP-ribose) Polymerase Inhibitors - pharmacology
• ISSN: 0308-8146; 1873-7072; 1873-7072
• DOI: 10.1016/j.foodchem.2016.01.060

•Myristica fragrans, a highly consumed spice for its culinary and medicinal properties.•The present study discovered a new acyclic with K-Ras activity that can be chemically optimized.•This is the first report of neolignans from M. fragrans with PARP-1 and NF-κB inhibitory effects. 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-[(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). 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) (IC50=3.04μM), compound (2) (IC50=0.001μM), compound (4) (IC50=22.07μM) and compound (5) (IC50=3.11μM). 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 (IC50=1.5 nM and 3.4nM, respectively).