Synthesis and antiproliferative activity of culicinin D analogues containing simplified AHMOD-based residues

Eur J Med Chem. 2019 Sep 1;177:235-246. doi: 10.1016/j.ejmech.2019.05.052. Epub 2019 May 23.

Abstract

Culicinin D is a 10 amino acid peptaibol containing a rare and synthetically challenging (2S,4S,6R)-AHMOD residue, that exhibits potent antiproliferative activity against MDA-MB-468 cells. An SAR study focusing on replacement of the AHMOD residue was undertaken, culminating in the revelation that a 6-hydroxy or 6-keto substituent was essential to retain potent low nanomolar antiproliferative activity.

Keywords: AHMOD; Cancer; Culicinin D; Peptaibol; Toxin.

MeSH terms

  • Amino Acid Substitution
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Decanoic Acids / chemistry
  • Drug Screening Assays, Antitumor
  • Humans
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Peptaibols / chemical synthesis
  • Peptaibols / chemistry
  • Peptaibols / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid
  • Antineoplastic Agents
  • Decanoic Acids
  • Oligopeptides
  • Peptaibols
  • culicinin D