title: Constituents of the stems of Macrococculus pomiferus and their inhibitory activities against cyclooxygenases-1 and -2.
abstract: As part of our program directed towards the discovery of new cancer chemopreventive agents from plants, the EtOAc-soluble extract of the stems of M. pomiferus was found to inhibit the enzyme cyclooxygenase-2 (COX-2). Bioassay-directed fractionation of this extract led to the isolation of two dibenzylbutyrolactone lignans, (8R,8'R)-3'-O-demethyl-5-hydroxymatairesinol (1) and (8R,8'R)-3'-O-demethyl-5-methoxymatairesinol (2), as well as seven known compounds, (-)-5'-methoxyyatein (3), blumenol A, (-)-deoxypodophyllotoxin (anthricin), (-)-deoxypodorhizone, 2,6-dimethoxyhydroquinone, 4-hydroxybenzaldehyde, and beta-sitosterol glucoside. The structures of compounds 1 and 2 were determined using spectroscopic data (1D and 2D NMR, and HREIMS), and the 8R and 8'R absolute stereochemistry was established for both 1 and 2 on the basis of their CD spectra. All isolates obtained in the present study were evaluated for their inhibitory effects with both COX-1 and -2. Of these, only 5'-methoxyyatein (3) showed weak activity against COX-2, while all other compounds isolated were inactive. The COX-2 inhibitory activity of the EtOAc extract was also traced to the presence of several common fatty acids by LC-MS.
authors.affiliation: Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Bao-Ning
authors.initials: BN
authors.lastname: Su
authors.forename: William P
authors.initials: WP
authors.lastname: Jones
authors.forename: Muriel
authors.initials: M
authors.lastname: Cuendet
authors.forename: Leonardus B S
authors.initials: LB
authors.lastname: Kardono
authors.forename: Rachman
authors.initials: R
authors.lastname: Ismail
authors.forename: Soedarsono
authors.initials: S
authors.lastname: Riswan
authors.forename: Harry H S
authors.initials: HH
authors.lastname: Fong
authors.forename: Norman R
authors.initials: NR
authors.lastname: Farnsworth
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D029583:Menispermaceae / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018547:Plant Stems / Q000737:chemistry*; D011451:Prostaglandin-Endoperoxide Synthases
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D010936:Plant Extracts; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases