Svalbamides A and B, Pyrrolidinone-Bearing Lipodipeptides from Arctic Paenibacillus sp

Mar Drugs. 2021 Apr 17;19(4):229. doi: 10.3390/md19040229.

Abstract

Two new secondary metabolites, svalbamides A (1) and B (2), were isolated from a culture extract of Paenibacillus sp. SVB7 that was isolated from surface sediment from a core (HH17-1085) taken in the Svalbard archipelago in the Arctic Ocean. The combinational analysis of HR-MS and NMR spectroscopic data revealed the structures of 1 and 2 as being lipopeptides bearing 3-amino-2-pyrrolidinone, d-valine, and 3-hydroxy-8-methyldecanoic acid. The absolute configurations of the amino acid residues in svalbamides A and B were determined using the advanced Marfey's method, in which the hydrolysates of 1 and 2 were derivatized with l- and d- forms of 1-fluoro-2,4-dinitrophenyl-5-alanine amide (FDAA). The absolute configurations of 1 and 2 were completely assigned by deducing the stereochemistry of 3-hydroxy-8-methyldecanoic acid based on DP4 calculations. Svalbamides A and B induced quinone reductase activity in Hepa1c1c7 murine hepatoma cells, indicating that they represent chemotypes with a potential for functioning as chemopreventive agents.

Keywords: 3-amino-2-pyrrolidinone; Arctic; DP4 calculation; Marfey’s method; Paenibacillus; Svalbard; lipopeptide; quinone reductase.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / isolation & purification
  • Anticarcinogenic Agents / pharmacology*
  • Arctic Regions
  • Bacterial Proteins / isolation & purification
  • Bacterial Proteins / pharmacology*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / enzymology
  • Cell Line, Tumor
  • Ecosystem
  • Geologic Sediments / microbiology
  • Humans
  • Lipopeptides / isolation & purification
  • Lipopeptides / pharmacology*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / enzymology
  • Mice
  • Molecular Structure
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Paenibacillus / metabolism*
  • Structure-Activity Relationship

Substances

  • Anticarcinogenic Agents
  • Bacterial Proteins
  • Lipopeptides
  • NAD(P)H Dehydrogenase (Quinone)