Isolation of aerucyclamides C and D and structure revision of microcyclamide 7806A: heterocyclic ribosomal peptides from Microcystis aeruginosa PCC 7806 and their antiparasite evaluation

Abstract

Aerucyclamides C and D were isolated from the cyanobacterium Microcystis aeruginosa PCC 7806, and their structures established by NMR spectroscopy and chemical transformation and degradation. Acidic hydrolysis of aerucyclamide C (CF(3)CO(2)H, H(2)O) resulted in microcyclamide 7806A. This chemical evidence combined with spectroscopic and physical data suggest a structure revision for microcyclamide 7806A, which incorporates an O-acylated Thr ammonium residue instead of the originally proposed methyl oxazoline ring. We have prepared microcyclamide 7806B upon basic and acidic treatment of microcyclamide 7806A, which suggests that both these compounds are hydrolysis products of aerucyclamide C and that the aerucyclamides A-D are the actual metabolites produced via ribosomal peptide synthesis in M. aeruginosa PCC 7806. Antiplasmodial evaluation established submicromolar IC(50) values for aerucyclamide B against Plasmodium falciparum; low micromolar values for aerucyclamide C were found against Trypanosoma brucei rhodesiense. The compounds were selective for the parasites over a cell line of L6 rat myoblasts and are thus considered for further study as antimalarial agents.