title: Synthesis and biological evaluation of a library of resveratrol analogues as inhibitors of COX-1, COX-2 and NF-kappaB.
abstract: Resveratrol (4,3',5'-trihydroxystilbene) is a naturally occurring antioxidant that inhibits cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and the transcription factor NF-kappaB. A 78-membered library of resveratrol analogues in which the substituents on the two aryl rings and alkene were varied was synthesized using a solid-phase Wittig olefination reaction. The library contains inhibitors against all three proteins that were more potent than resveratrol itself. Preliminary structure-activity relationships were also obtained from these data that permitted the derivation of pharmacophore models for each of the three targets.
authors.affiliation: Department of Chemistry, The Purdue Cancer Center, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA.
authors.forename: Soo Sung
authors.initials: SS
authors.lastname: Kang
authors.forename: Muriel
authors.initials: M
authors.lastname: Cuendet
authors.forename: Denise C
authors.initials: DC
authors.lastname: Endringer
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Croy
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lipton
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D020650:Combinatorial Chemistry Techniques; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077185:Resveratrol; D054852:Small Molecule Libraries; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016328:NF-kappa B; D054852:Small Molecule Libraries; D013267:Stilbenes; D000077185:Resveratrol