Selective inhibition of separated forms of cyclic nucleotide phosphodiesterase from rat heart by some pentasubstituted quercetin analogs.
Synthetic analogs of quercetin were evaluated as inhibitors of cyclic nucleotide phosphodiesterase in rat heart preparations. Three main enzymatic forms of cyclic nucleotide phosphodiesterase can be resolved from rat heart cytosol by isoelectric focusing. Inhibition studies were performed with the whole cytosolic and particulate preparations and with the cytosolic separated enzymatic forms. All the compounds studied proved more potent as inhibitors of the particular preparation than as inhibitors of the cytosolic fraction. With the exception of water-soluble derivatives and quercetin, they showed a better potency to inhibit cyclic AMP than cyclic GMP phosphodiesterase activity of the cytosolic and particulate preparations; likewise, among the three separated enzymatic forms, the cyclic AMP specific form of pI 5.55-6 is the most inhibited by these flavonoid compounds. In all cases, the highest selectivity was observed with pentaethyl quercetin (2).
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D005419:Flavonoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology*; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D005419:Flavonoids; D011794:Quercetin; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases