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

  • J Nat Prod. 2022 Mar 25;85(3):501-510. doi: 10.1021/acs.jnatprod.1c01102.
Changyeol Lee  1 ,  Junpyo Gong  2 ,  Jaekyeong Kim  2 ,  Hyejin Ko  2 ,  Seungchan An  2 ,  Sunghee Bang  1 ,  Stephen T Deyrup  3 ,  Minsoo Noh  2 ,  Sang Hee Shim  2
Affiliations
  • 1. College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea.
  • 2. Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
  • 3. Department of Chemistry and Biochemistry, Siena College, Londonville, New York 12211, United States.
PMID: 35172097 DOI: 10.1021/acs.jnatprod.1c01102
Abstract

Three new cyclic peptide-polyketide hybrids (1-3) and two new chaetiacandin-type polyketides (4 and 5) along with nine known compounds were isolated from cultures of a halophyte-associated fungus, Colletotrichum gloeosporioides JS0417. Spectroscopic analysis revealed that 1-3 were cyclic depsipeptides where 3,5,11-trihydroxy-2,6-dimethyldodecanoic acid was linked to two Amino acids through amide and ester bonds to form a 12-membered ring. Relative and absolute configurations for the peptides were determined with spectroscopic analysis and chemical reactions. The cyclic depsipeptides 2 and 6 were determined to act as strong adiponectin-secretion-promoting modulators with potential to treat metabolic diseases associated with hypoadiponectinemia. Notably, a known compound, tryptophol, significantly inhibited PGE2 synthesis and also promoted Adiponectin secretion, exhibiting a similar biological activity profile to aspirin, but with greater potency. The presence of an isoleucine moiety and non-glycosylation may be important for biological activity of the cyclic peptide-polyketide hybrids, and non-methoxylation of the side chain may influence activity of the indole derivatives.