-Eurystatins A and B, which are produced by Streptomyces eurythermus R353-21, potently inhibited Flavobacterium prolyl endopeptidase (PED) with IC50 values of 0.004 and 0.002,ug/ml, res pectively, while no inhibition was observed against another 5 proteases, even at 100 1tg/ml. The pro tective effect of eurystatins A and B against scopolamine (3 mg/kg, i.p.)-induced amnesia in rats was evaluated by the step-through one-trial passive avoidance method. When administered i.p. 30 min prior to the acquisition trial, both eurystatins A, at 2 8 mg/kg, and B, at 4 8 mg/kg, significantly protected rats from the amnesic effect of scopolamine without behavioral side effects.

DynemicinA showedextremely potent in vitro cytotoxicity against a variety of murine and human tumor cells. In the experimental animal tumor models implanted ip with P388, L1210leukemias and B16 melanoma cells, dynemicin A administered ip significantly prolonged life-span of tumor-bearing mice with the wide range of activity. This antibiotic administered iv wasalso active against iv implanted P388 and L1210 leukemias. In the macromolecule biosynthesis of B16 melanoma cells, dynemicin A inhibited DNAsynthesis specifically. The triacetyl derivative exhibited similar in vitro and in vivo antitumor activities to those of the parent antibiotic.

EurystatinsA and B, were isolated from the cultured broth of Streptomyces eurythermus R353-21. They showed specific and potent inhibitory activity against prolyl endopeptidase and did not showantimicrobial activity. No lethal toxicity was observed for the two compoundsafter ip administration in mice at 200mg/kg.