Structure-activity relationships of 11 new congeners of the SMTP plasminogen modulator

The fungal metabolite Stachybotrys microspora triprenyl phenols (SMTPs) are small-molecule plasminogen modulators that enhance plasminogen activation. The SMTP molecule consists of a tricyclic γ-lactam moiety, an isoprene side-chain and an N-linked side-chain. Previous investigations have demonstrated that the N-linked side-chain is crucial for its activity. In this study, we have isolated 11 new SMTP congeners with a variety of N-linked side-chain structures, to investigate structure-activity relationships. Active compounds included congeners with a carboxyl or a sulfonic acid group in the N-linked side-chain, whereas not all the congeners with a carboxyl group were active. Of these congeners, that with methionine or tyrosine as the N-linked side-chain moiety was more active than that with an aliphatic amino acid. Congeners without ionizable group in the N-linked side-chain were essentially inactive.