Complete NMR assignment and absolute configuration of k4610422, a norditerpenoid inhibitor of testosterone-5α-reductase originally from Streptosporangium: rediscovery from a thermophilic Actinomadura

J Antibiot (Tokyo). 2020 Jan;73(1):60-65. doi: 10.1038/s41429-019-0231-7. Epub 2019 Sep 3.

Abstract

A norditerpenoid k4610422 (1), an inhibitor of testosterone-5α-reductase originally discovered from a mesophilic rare actinomycete of the genus Streptosporangium, was isolated from the culture extract of a thermophilic actinomycete Actinomadura sp. The complete 1H and 13C NMR assignment and absolute configuration of 1 were addressed by spectroscopic measurements including NOESY and CD spectra coupled with ECD calculation, which allowed to establish the (5 R,9 S,10 R,13 S)-configuration. Compound 1 was moderately cytotoxic against P388 murine leukemia cells with IC50 30 μM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / drug effects*
  • Actinomycetales / chemistry*
  • Androgen Antagonists / chemistry*
  • Androgen Antagonists / pharmacology*
  • Animals
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects
  • Circular Dichroism
  • Diterpenes
  • Fermentation
  • Leukemia P388 / drug therapy
  • Magnetic Resonance Spectroscopy
  • Microbial Sensitivity Tests

Substances

  • Androgen Antagonists
  • Anti-Bacterial Agents
  • Diterpenes
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase