Aza-cycloisodityrosine analogue of RA-VII, an antitumor bicyclic hexapeptide

Bioorg Med Chem Lett. 2013 Dec 15;23(24):6728-31. doi: 10.1016/j.bmcl.2013.10.033. Epub 2013 Oct 26.

Abstract

An aza-cycloisodityrosine analogue of RA-VII, 3, was designed and synthesized. The key aza-cycloisodityrosine unit was prepared by copper(II)-acetate-mediated intramolecular phenylamine/arylboronic acid coupling of dipeptide followed by connection with the tetrapeptide segment to afford a hexapeptide. Subsequent macrocyclization of the hexapeptide with EDC · HCl and HOOBt under dilute conditions gave 3. Analogue 3 showed significant cytotoxic activity against human promyelocytic leukemia HL-60 cells and human colon carcinoma HCT-116 cells, but its activity was weaker than that of parent peptide RA-VII (1).

Keywords: Aza-cycloisodityrosine; Bouvardin; Cytotoxicity; RA-VII; Rubia cordifolia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemical synthesis
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / toxicity
  • Aza Compounds / chemistry
  • Crystallography, X-Ray
  • HCT116 Cells
  • HL-60 Cells
  • Humans
  • Molecular Conformation
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / toxicity
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / toxicity
  • Rubia / chemistry
  • Rubia / metabolism
  • Tyrosine / analogs & derivatives*
  • Tyrosine / chemical synthesis
  • Tyrosine / chemistry
  • Tyrosine / toxicity

Substances

  • Antineoplastic Agents, Phytogenic
  • Aza Compounds
  • Peptides
  • Peptides, Cyclic
  • bouvardin
  • Tyrosine
  • isodityrosine
  • RA VII