title: SAR: flavonoids and COX-2 inhibition.
abstract: An analysis based upon structure-activity relationships (SAR) of the COX-2-inhibiting properties of flavonoids, a group of potential cancer chemopreventative agents, reveals that there is a dual structural basis for these activities. Each of these structural determinants (pharmacophores) alone is sufficient for activity. One of the pharmacophores is a 2D 6.9 A distance descriptor that spans the A and C rings and includes the 4-OXO and 7-hydroxyl moieties. The potency associated with that pharmacophore is determined by a series of structural modulators that can increase, decrease, or even abolish the COX-2-inhibiting potential associated with that pharmacophore. The second pharmacophore describes a para-substituted phenolic B ring that requires unsubstituted meta and ortho positions. Based upon this, it indicates that hydroxylation at the 4'-position and a free 5'-position are sufficient for COX-2-inhibiting activity. The potency associated with this pharmacophore is modulated by log P2 and by the molecular weight.
authors.affiliation: Department of Biomedical Sciences, Florida Atlantic University, Boca Raton, FL 33431-0991, USA. rosenkra@fau.edu
authors.forename: Herbert S
authors.initials: HS
authors.lastname: Rosenkranz
authors.forename: Bhavani P
authors.initials: BP
authors.lastname: Thampatty
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D051546:Cyclooxygenase 2; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005419:Flavonoids / Q000138:chemical synthesis* / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D011451:Prostaglandin-Endoperoxide Synthases; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases