New glycosylated derivatives of versipelostatin, the GRP78/Bip molecular chaperone down-regulator, from Streptomyces versipellis 4083-SVS6

Four novel glycosylated derivatives of versipelostatin (1), versipelostatins B-E (2-5), were isolated from the culture broth of Streptomyces versipellis 4083-SVS6. The inhibitory activities of the isolated compounds against the expression of molecular chaperone GRP78 induced by 2-deoxyglucose were evaluated. Of the five versipelostatin family members, 1 and 4 were the more potent with IC50 values of 3.5 and 4.3 mu M. These results suggest that the alpha-L-oleandropyranosyl (1 -> 4)-beta-D-digitoxopyranosyl residue in the sugar moiety may play an important role in down-regulating GRP78 expression induced by 2-deoxyglucose.