Neo-actinomycins A and B, natural actinomycins bearing the 5H-oxazolo[4,5-b]phenoxazine chromophore, from the marine-derived Streptomyces sp. IMB094

Sci Rep. 2017 Jun 15;7(1):3591. doi: 10.1038/s41598-017-03769-8.

Abstract

Neo-actinomycins A and B (1 and 2), two new natural actinomycins featuring an unprecedented tetracyclic 5H-oxazolo[4,5-b]phenoxazine chromophore, were isolated from the marine-derived actinomycete Streptomyces sp. IMB094. Their structures were elucidated by spectroscopic analyses. The presence of this ring system was proposed to originate from a condensation between actinomycin D (3) with α-ketoglutarate and pyruvate, respectively. Compound 1 showed potent cytotoxic activities against human cancer HCT116 and A549 cell lines in the nanomolar range (IC50: 38.7 and 65.8 nM, respectively) and moderate antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification*
  • Anti-Bacterial Agents / pharmacology
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / isolation & purification*
  • Antibiotics, Antineoplastic / pharmacology
  • Aquatic Organisms / chemistry*
  • Aquatic Organisms / isolation & purification
  • Biological Products / chemistry
  • Biological Products / isolation & purification*
  • Biological Products / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dactinomycin / chemistry
  • Dactinomycin / isolation & purification*
  • Dactinomycin / pharmacology
  • Enterococcus / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Spectrum Analysis
  • Staphylococcus aureus / drug effects
  • Streptomyces / chemistry*
  • Streptomyces / isolation & purification

Substances

  • Anti-Bacterial Agents
  • Antibiotics, Antineoplastic
  • Biological Products
  • Dactinomycin