Synthesis and structure-activity relationships of new 9-N-alkyl derivatives of 9(S)-erythromycylamine.

A series of new 9-N-alkyl derivatives of 9(S)-erythromycylamine has been synthesized by reductive alkylation of erythromycylamine with aliphatic aldehydes and sodium cyanoborohydride. Alternative syntheses employing hydrogenation methods have also been developed. These new 9-N-alkyl derivatives possess excellent antimicrobial activity in vitro and in vivo, especially when administered orally to treat experimental infections in mice. From structure-activity studies, 9-N-(1-propyl)erythromycylamine (LY281389) was selected as the most efficacious derivative. These methods have also been extended to the synthesis of some 9-N,N-dialkyl derivatives of erythromycylamine.info:eu-repo/semantics/publishe

Multiple Toxin Production in the Cyanobacterium Microcystis : Isolation of the Toxic Protease Inhibitor Cyanopeptolin 1020

The isolation and structure of cyanopeptolin 1020 (hexanoic acid-Glu-N[-O-Thr-Arg-Ahp-Phe-N-Me-Tyr-Val-]) from a Microcystis strain is reported. Very potent picomolar trypsin inhibition (IC50 = 670 pM) and low nanomolar values against human kallikrein (4.5 nM) and factor XIa (3.9 nM) have been determined for cyanopeptolin 1020. For plasmin and chymotrypsin, low micromolar concentrations were necessary for 50% inhibition. Cyanopeptolin 1020 was found to be toxic against the freshwater crustaceanThamnocephalus platyurus (LC50 = 8.8 μM), which is in the same range as some of the well-known microcystins. These data support the hypothesis that cyanopeptolins can be considered as a second class of toxins in addition to the well-established microcystins inMicrocystis