Abstract
The organic extract of the fermentation broth of an unidentified fungus was found to contain three epidermal growth factor (EGF) receptor anagonists: SCH 64874 ( 1), SCH 64875 ( 2), SCH 64877 ( 3). These compounds belong to a family of thiodiketopiperazine derivatives and are esters of an eight carbon aliphatic acid, 2,4- dimethyl-3-hydroxyhexanoic acid and a thiodiketopiperazine, aranotin. They exhibited potent EGF receptor antagonist activity. The IC 50 in EGF receptor assays for compounds 1, 2 and 3 are 1.0, 1.0 and 1.25 μg/ml, respectively.
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