Griseolic acid, an inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase. I. Taxonomy, isolation and characterization.

Griseolic acid, a potent inhibitor of cyclic adenosine 3',5'-monophosphate (cyclic AMP) phosphodiesterase (EC 3.1.4.17) was isolated from the cultured broth of Streptomyces griseoaurantiacus SANK 63479. Griseolic acid has an adenine moiety and two carboxyl groups and possesses the molecular formula C14H13N5O8. Griseolic acid inhibited cyclic AMP phosphodiesterase competitively with regard to cyclic AMP, the substrate and the resulting Ki value was 0.26 microM. Griseolic acid showed the most potent inhibitory effect on rat aorta cyclic AMP phosphodiesterase among the enzymes of several rat organs tested. The plasma level of cyclic AMP was increased when griseolic acid was subcutaneously injected rats.