A new actinomycin Z analogue with an additional oxygen bridge between chromophore and β-depsipentapeptide from Streptomyces sp. KIB-H714

Nat Prod Res. 2019 Jan;33(2):219-225. doi: 10.1080/14786419.2018.1443097. Epub 2018 Mar 2.

Abstract

Actinomycin Z6 (1), a new member of the actinomycin family, along with three congeners of the Z-type (Z1, Z3, Z5) actinomycins, are produced from Streptomyces sp. KIB-H714. Their structures were authenticated by comprehensive spectroscopic data interpretation. Different from all the reported Z-type actinomycins, the β-ring of the new compound actinomycin Z6 includes an additional ring linked between the actinoyl chromophore and β-peptidolactone. In Z3 and Z5, the L-threonine in β-depsipeptide is replaced by the unusual 4-chlorothreonine, an amino acid rarely found in actinomycin family. All isolates were evaluated for cytotoxicity against five human tumor cell lines and for inhibitory activity against Candida albicans and Staphylococcus aureus.

Keywords: Actinomycin; antibacterial activity; cytotoxicity; structure elucidation.

MeSH terms

  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Candida albicans / drug effects
  • Cell Line, Tumor
  • Dactinomycin / analogs & derivatives*
  • Dactinomycin / chemistry
  • Dactinomycin / pharmacology*
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Oxygen / chemistry
  • Spectrometry, Mass, Electrospray Ionization
  • Staphylococcus aureus / drug effects
  • Streptomyces / chemistry*
  • Structure-Activity Relationship
  • Threonine / analogs & derivatives
  • Threonine / chemistry

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents
  • 4-chlorothreonine
  • Dactinomycin
  • Threonine
  • Oxygen