The antiviral, antitumoural xanthate D609 is a competitive inhibitor of phosphatidylcholine-specific phospholipase C.
The effect of the antiviral, antitumoural xanthate D609 on the activity of phospholipase A2, C (PC- and Pi-specific) and D was investigated. D609 is the first model substance of a new concept of antiviral therapy that interferes with cellular regulation mechanisms, rather than with virus coded enzymes. Exclusively phosphatidylcholine (PC) specific phospholipase C (PC-PLC) was found to be inhibited in a dose-dependent manner. Enzyme activity was determined either as the rate of acid release from PC or as the rate of phosphorylcholine production form 3H labelled PC. Lineweaver-Burk plots revealed D609 as a competitive inhibitor of PC-PLC with a Ki of 6.4 microM. In addition, D609 competitively inhibited PC-PLC mediated cleavage of P-nitrophenylphosphorylcholine (p-NPP), a pseudo-substrate of PC-PLC with a Ki of 8.8 microM. These data suggest that D609 competes with the phosphorylcholine residue of PC for binding to PC-PLC.
Amtmann
E
E
German Cancer Research Centre, Heidelberg, Germany.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002417:Cattle; D009636:Norbornanes; D010713:Phosphatidylcholines / Q000378:metabolism; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001952:Bridged-Ring Compounds; D009636:Norbornanes; D010713:Phosphatidylcholines; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D010738:Type C Phospholipases