Total structure and inhibition of tumor cell proliferation of laxaphycins

J Med Chem. 2007 Mar 22;50(6):1266-79. doi: 10.1021/jm061307x. Epub 2007 Feb 27.

Abstract

From a mixed assemblage of Lyngbya majuscula rich marine cyanobacteria, we isolated a series of cell growth inhibitory cyclic peptides. The structures of the two major components, laxaphycins A (1) and B (2), and of two minor peptides, laxaphycins B2 (3) and B3 (4), were determined by spectroscopic methods and degradative analysis. Absolute configurations of natural and nonproteinogenic amino acids were determined by a combination of hydrolysis, synthesis of noncommercial residues, chemical derivatization, and HPLC analysis. The organism producing the laxaphycins was identified as the cyanobacterium Anabaena torulosa. The antiproliferative activity of laxaphycins was investigated on a panel of solid and lymphoblastic cancer cells. Our results demonstrate that in contrast to laxaphycin A, laxaphycin B inhibits the proliferation of sensitive and resistant human cancer cell lines and that this activity is strongly increased in the presence of laxaphycin A. This effect appears to be due to an unusual biological synergism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anabaena / chemistry*
  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chromatography, High Pressure Liquid
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Humans
  • Hydrolysis
  • Magnetic Resonance Spectroscopy
  • Mice
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / isolation & purification
  • Peptides, Cyclic / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Laxaphycin A
  • Laxaphycin B
  • Peptides, Cyclic
  • laxaphycin B2
  • laxaphycin B3