SELECTIVE-INHIBITION OF RAT-HEART CAMP PHOSPHODIESTERASES BY LIPOPHILIC C-METHYL-2-PHENYL-4H-1-BENZOPYRAN-4-ONES (C-METHYLFLAVONES)

A series of eight methoxylated C-methyl-2-phenyl-4H-1-benzopyran-4-one s 3, 6, 10-15 was evaluated as inhibitors of rat heart cytosolic cycli c nucleotide phosphodiesterase (PDE). The )-5,7-dimethoxy-3,8-dimethyl -4H-1-benzopyran-4-one (3) and the )-5,7-dimethoxy-3,8-dimethyl-4H-1-b enzopyran-4-one (10) have never been previously described. Inhibition was performed on the whole cytosolic preparation and on the four PDE i soforms 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 cAM P. The di-C-methylflavones 3 and 13 have been shown to be potent inhib itors of these two isoforms, with IC50 values in the micromolar range.