title: Selective inhibition of rat heart cAMP phosphodiesterases by lipophilic C-methyl-2-phenyl-4H-1-benzopyran-4-ones (C-methylflavones).
abstract: A series of eight methoxylated C-methyl-2-phenyl-4H-1-benzopyran-4-ones 3, 6, 10-15 was evaluated as inhibitors of rat heart cytosolic cyclic nucleotide phosphodiesterase (PDE). The 2-(3,4-dimethoxyphenyl)-5,7-dimethoxy-3,8-dimethyl-4H-1-benzopyran-4-one (3) and the 2-(4-methoxyphenyl)-5,7-dimethoxy-3,8-dimethyl-4H-1-benzopyran-4-one (10) have never been previously described. Inhibition was performed on the whole cytosolic preparation and on the four PDE isoforms after HPLC purification. The flavones 3, 6, 10, 13 and 14 were selective and potent inhibitors of the isoforms, namely ROI (rolipram-sensitive) and CGI (cGMP-sensitive) PDEs specifically hydrolyzing cAMP. The di-C-methylflavones 3 and 13 have been shown to be potent inhibitors of these two isoforms, with IC50 values in the micromolar range.
authors.affiliation: Laboratoire de Biochimie Analytique et de Synthèse Bioorganique, Université Claude Bernard-Lyon I, Villeurbanne, France.
authors.forename: P
authors.initials: P
authors.lastname: Gaillard
authors.forename: M
authors.initials: M
authors.lastname: Hauteville
authors.forename: M
authors.initials: M
authors.lastname: Picq
authors.forename: M C
authors.initials: MC
authors.lastname: Duclos
authors.forename: M
authors.initials: M
authors.lastname: Dubois
authors.forename: A F
authors.initials: AF
authors.lastname: Prigent
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005419:Flavonoids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D005419:Flavonoids; D007527:Isoenzymes; D015105:3',5'-Cyclic-AMP Phosphodiesterases