A NOVEL CLASS OF PLATELET-ACTIVATING-FACTOR ANTAGONISTS FROM PHOMA SP

Four novel platelet activating factor (PAF) antagonists, Sch 47918, Sc h 49026, Sch 49027 and Sch 49028, were isolated from the fermentation broth of the fungal culture, Phoma sp. (ATCC 74077). The structures of these compounds were elucidated by spectroscopic methods. The structu re and stereochemistry of the first isolated component, Sch 47918, wer e confirmed by single crystal X-ray diffraction analysis. Sch 49028, t he most active component, was found to inhibit PAF-induced human plate let aggregation in vitro with an IC50 of 1.26 mum. However, this compo und was inactive in vivo at 5 mg/kg, iv against PAF-induced bronchospa sm in guinea pigs.