Adiponectin-Secretion-Promoting Cyclic Peptide-Polyketide Hybrids from a Halophyte-Associated Fungus, Colletotrichum gloeosporioides JS0417

Abstract

Three new cyclic peptide-polyketide hybrids (1-3) and two new chaetiacandin-type polyketides (4and5) along with nine known compounds were isolated from cultures of ahalophyte-associated fungus,Colletotrichum gloeosporioidesJS0417.Spectroscopic analysis revealed that1-3were cyclic depsipeptideswhere 3,5,11-trihydroxy-2,6-dimethyldodecanoic acid was linked totwo amino acids through amide and ester bonds to form a 12-membered ring. Relative and absolute configurations for thepeptides were determined with spectroscopic analysis and chemicalreactions. The cyclic depsipeptides2and6were determined to actas strong adiponectin-secretion-promoting modulators withpotential to treat metabolic diseases associated with hypoadiponectinemia. Notably, a known compound, tryptophol, significantlyinhibited PGE2synthesis and also promoted adiponectin secretion, exhibiting a similar biological activity profile to aspirin, but withgreater potency. The presence of an isoleucine moiety and non-glycosylation may be important for biological activity of the cyclicpeptide-polyketide hybrids, and non-methoxylation of the side chain may influence activity of the indole derivatives