Synthesis and biological evaluation of a library of resveratrol analogues as inhibitors of COX-1, COX-2 and NF-kappaB.
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.
Kang
Soo Sung
SS
Department of Chemistry, The Purdue Cancer Center, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA.
Cuendet
Muriel
M
Endringer
Denise C
DC
Croy
Vicki L
VL
Pezzuto
John M
JM
Lipton
Mark A
MA
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
D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016328:NF-kappa B; D054852:Small Molecule Libraries; D013267:Stilbenes; D000077185:Resveratrol