Structure/activity studies of flavonoids as inhibitors of cyclic AMP phosphodiesterase and relationship to quantum chemical indices.

摘要: A series of 45 flavonoids and related compounds were tested as inhibitors liver fluke cyclic nucleotide phosphodiesterase. Many found to be potent inhibitors; seven or more than any inhibitor previously tested. The kinetics six spanning a wide range activities investigated competitive. most inhibitors, cyanidin chloride quercetin, had Ki values 10 ± 3 µM 13 6 µM, respectively, approaching the Km for CAMP (8 µM). Structure/ activity studies showed that adding exocyclic substituents basic flavonoid skeleton affected only slightly, while changing planarity heterocyclic ring greatly decreased activity. This observation, taken with competitive kinetics, suggests compete cAMP binding site at which stacking occurs, perhaps similar sites bovine pancreatic ribonuclease lobster glyceraldehyde-3-phosphate dehydrogenase. Quantum chemical calculations further suggest competition arises from mimicking pyrimidine in by pyranone flavonoids. If are comparably other phosphodiesterases, several reported pharmacological effects might explained.