title: Highly potent oligostilbene sbLOX-1 inhibitor from Gnetum macrostachyum.
abstract: Isolated oligostilbenes from G. macrostachyum exhibited sbLOX-1 inhibitory activity with IC50 values ranging from 0.14-11.91 microM. Of these oligostilbenoids, 12 (IC50 0.14 +/- 0.01 microM), 10 (IC50 0.33 +/- 0.11 microM), 11 (IC50 0.49 +/- 0.05 microM) and 7 (IC50 1.03 +/- 0.43 microM) were more active than nordihydroguaiaretic acid (NDGA) (P < 0.05) which was the positive control. The enzyme kinetic analysis revealed that 7 and 11 inhibited sbLOX-1 noncompetitively with Ki values of 11.2 and 71.4 nM. Compound 10 inhibited sbLOX-1 through mixed-competitive mechanisms (Ki = 13.8 nM and Ki' 56.7 nM). Moreover, 12 was an uncompetitive inhibitor with a Ki value of 0.8 nM. The inhibitory activity of oligostilbenes did not result from the antioxidant property, as demonstrated by DPPH and 13-HPOD scavenging assays. These compounds also showed ferric reducing capabilities, but had no effect in a Fe(3+)-bound sbLOX-1 model, as indicated by UV spectrophotometric and CD spectroscopic studies.
authors.forename: Serm
authors.initials: S
authors.lastname: Surapinit
authors.forename: Piyawit
authors.initials: P
authors.lastname: Sri-In
authors.forename: Santi
authors.initials: S
authors.lastname: Tip-Pyang
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000737:chemistry; D035684:Gnetum / Q000737:chemistry*; D006861:Hydrogen Peroxide; D007501:Iron / Q000737:chemistry; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010851:Picrates / Q000737:chemistry; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D016859:Lipoxygenase Inhibitors; D010851:Picrates; D013267:Stilbenes; D006861:Hydrogen Peroxide; C004931:1,1-diphenyl-2-picrylhydrazyl; D007501:Iron; D008084:Lipoxygenase