INHIBITION OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 ACTIVITY BY 2 DIKETOPIPERAZINES, XR330 AND XR334 PRODUCED BY STREPTOMYCES SP

Two diketopiperazines, XR334 (1) and the novel compound XR330 (2) were isolated from the lyophilised biomass of an unidentified Streptomyces sp. Their structures were elucidated on the basis of spectroscopic st udies and confirmed by chemical synthesis. Both compounds inhibited pl asminogen activator inhibitor-1 activity in an amidolytic assay of tis sue plasminogen activator mediated plasmin generation. Compound 1 also enhanced fibrinolysis ex vivo and protected against thrombus formatio n in the rat. These diketopiperazines represent the first low molecula r weight inhibitors of plasminogen activator inhibitor-1, a physiologi cal regulator of fibrinolysis