Synthesis and antiproliferative activity of C- and N-terminal analogues of culicinin D

Bioorg Med Chem Lett. 2020 Aug 15;30(16):127331. doi: 10.1016/j.bmcl.2020.127331. Epub 2020 Jun 9.


Culicinin D (1), a 10 amino acid peptaibol containing several unusual residues, has been shown to exhibit potent anticancer activity. Previous work in our group towards developing a structure-activity relationship (SAR) for this peptaibol has concentrated on replacement of the synthetically challenging AHMOD (3) and AMD (4) residues, resulting in the discovery of analogues with equivalent or better potency and simplified synthesis. The SAR of this peptaibol is extended in this work by investigating the effect of the N-terminal lipid tail and C-terminal amino alcohol, revealing the key contribution of each of these moieties on antiproliferative activity in a panel of breast and lung cancer cell lines.

Keywords: Cancer; Culicinin D; Peptaibol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Peptaibols / chemical synthesis
  • Peptaibols / chemistry
  • Peptaibols / pharmacology*
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • Oligopeptides
  • Peptaibols
  • culicinin D