Sch-37137

A new antifungal antibiotic, CB-25-I, was isolated from the culture broth of a strain of Serratia plymuthica. The antibiotic, a water-soluble dipeptide, is structurally related to Sch 37137 and A 19009, both produced by strains of Actinomycetales. The antibiotic exhibits inhibitory activity against Candida albicans in YNB medium (a synthetic medium), but the activity is significantly reduced in Sabouroud dextrose medium.

Peptide analogues of Sch 37137 the antifungal antibiotic have been synthesized and evaluated in vitro against Candida sp. Di- and tripeptides containing methionine, leucine, norvaline, lysine, glutamic acid and N3-(trans-epoxysuccinamoyl)-L-2,3-diaminopropanoic acid, (EADP) were obtained. Peptides containing (D)-, and (L)-trans-epoxysuccinamic acid were also prepared. All of the analogues examined displayed in general higher anticandidal activity than a mixture of diastereomers of Sch 37137.

Several analogs 5, 6, 7, 8, 10 and 11 of the C-terminal fragment of a peptide antibiotic Sch 37137 were designed and tested as inhibitors of glucosamine-6-phosphate synthase from Saccharomyces cerevisiae. From IC50 values and kinetic parameters of inhibition of glucosamine-6-phosphate synthase by compounds 5-11 it has been found that the inhibitory potency of these compounds follows the order: 6 > 5 > 8 > 9 > 7, 10, 11. This suggests that an inhibitor with a primary amido group binds better to the active site of the enzyme than other inhibitors. The order of reactivity of compounds 5-11 may be attributed to a steric inability of the inhibitor to fit into the active site of the enzyme and also indicates the importance of the chirality of trans-epoxysuccinic acid on the inhibitory properties of the synthesized compounds.