Studies toward the total synthesis of Itralamide B and biological evaluation of its structural analogs

Mar Drugs. 2015 Apr 13;13(4):2085-104. doi: 10.3390/md13042085.

Abstract

Itralamides A and B were isolated from the lipophilic extract of Lyngbya majuscula collected from the eastern Caribbean. Itralamide B (1) showed cytotoxic activity towards human embryonic kidney cells (HEK293, IC50 = 6 μM). Preliminary studies disapproved the proposed stereochemistry of itralamide. In this paper, we will provide a full account of the total synthesis of four stereoisomers of itralamide B and the results derived from biological tests of these structural congeners.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Caribbean Region
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyanobacteria / chemistry
  • Cyanobacteria / growth & development
  • Cyanobacteria / isolation & purification
  • Depsipeptides / chemical synthesis
  • Depsipeptides / chemistry
  • Depsipeptides / pharmacology*
  • Drug Design
  • Drug Discovery*
  • HEK293 Cells
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Lyngbya Toxins / chemical synthesis
  • Lyngbya Toxins / chemistry
  • Lyngbya Toxins / pharmacology*
  • Molecular Structure
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / toxicity
  • Osmolar Concentration
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / toxicity
  • Protein Conformation
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Depsipeptides
  • Lyngbya Toxins
  • Oligopeptides
  • Peptide Fragments
  • itralamide B