Rare Streptomyces N-formyl amino-salicylamides inhibit oncogenic K-Ras

Org Lett. 2014 Oct 3;16(19):5036-9. doi: 10.1021/ol502376e. Epub 2014 Sep 19.

Abstract

During a search for inhibitors of oncogenic K-Ras, we detected two known and two new examples of the rare neoantimycin structure class from a liquid cultivation of Streptomyces orinoci, and reassigned/assigned structures to all based on detailed spectroscopic analysis and microscale C3 Marfey's and C3 Mosher chemical degradation/derivatization/analysis. SAR investigations inclusive of the biosynthetically related antimycins and respirantin, and synthetic benzoxazolone, documented a unique N-formyl amino-salicylamide pharmacophore as a potent inhibitor of oncogenic K-Ras.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / drug effects
  • Depsipeptides / chemistry
  • Doxorubicin / pharmacology
  • Genes, ras / drug effects*
  • Molecular Structure
  • Organic Chemicals / chemistry
  • Salicylamides / chemistry*
  • Streptomyces / chemistry*
  • Structure-Activity Relationship

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Depsipeptides
  • Organic Chemicals
  • Salicylamides
  • respirantin
  • neoantimycin
  • Doxorubicin