Novel inhibitors of poly(ADP-ribose) glycohydrolase

The inhibitory effects on poly(ADP-ribose) glycohydrolase purified from human placenta of three classes of chemically defined tannins; gallotannins; ellagitannins and condensed tannins, were examined in vitro. Oligometric ellagitannins were found to be most potent inhibitors of poly(ADP-ribose) glycohydrolase, their potencies increasing with increasing number of monomeric residues (dinner <trimer <tetramer). Monomeric ellagitannins and gallotannins were less inhibitory. Condensed tannins, which consist of an epicatechin gallate oligomer without a glucose core, were not appreciably inhibitory. A structure-activity study showed that higher-order confirmations of the conjugates with glucose of hexahydroxydiphenoyl and valoneoyl groups, which are unique components of ellegitannins, cooperatively potentiated the inhibitory activity.