Synthesis and biological evaluation of the [d-MeAla(11)]-epimer of coibamide A

Bioorg Med Chem Lett. 2015 Jan 15;25(2):302-6. doi: 10.1016/j.bmcl.2014.11.044. Epub 2014 Nov 22.

Abstract

Coibamide A is a highly potent antiproliferative cyclic depsipeptide, which was originally isolated from a Panamanian marine cyanobacterium. In this study, the synthesis of coibamide A has been investigated using Fmoc-based solid-phase peptide synthesis followed by the cleavage of the resulting linear peptide from the resin and its subsequent macrolactonization. The peptide sequence of the linear coibamide A precursor was constructed on a solid-support following the optimization of the coupling conditions, where numerous coupling agents were evaluated. The macrocyclization of the resulting linear peptide provided the [d-MeAla(11)]-epimer of coibamide A, which exhibited nanomolar cytotoxic activity towards a number of human cancer cell lines.

Keywords: Antiproliferative peptide; Coibamide A; Depsipeptide; N-Methylamino acid.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects*
  • Depsipeptides / chemical synthesis*
  • Depsipeptides / pharmacology*
  • Humans
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Solid-Phase Synthesis Techniques
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Depsipeptides
  • coibamide A