Selective inhibition of rat heart cAMP phosphodiesterases by lipophilic C-methyl-2-phenyl-4H-1-benzopyran-4-ones (C-methylflavones)

Article abstract of DOI:10.1248/cpb.44.1571

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.

Full text of DOI:10.1248/cpb.44.1571

NII-Electronic Library Service

NII-Electronic Library Service

NII-Electronic Library Service

NII-Electronic Library Service

NII-Electronic Library Service

NII-Electronic Library Service