Synthesis and biological evaluation of distamycin analogues - new potential anticancer agents

Arch Pharm (Weinheim). 2009 Feb;342(2):87-93. doi: 10.1002/ardp.200800122.

Abstract

Eight of analogues of distamycin, potential minor-groove binders, were synthesized and tested for in-vitro cytotoxicity towards human breast cancer cells MCF-7 and MDA-MB-231. The method of synthesis is simple and convenient. All of the compounds 1-8 showed antiproliferative and cytotoxic effects against both cell lines in the range 3.47 to 12.53 microM for MDA-MB-231 and 4.35 to 12.66 microM for MCF-7. All compounds demonstrated activity against DNA topoisomerases I and II at a concentration of 50 microM. The ethidium bromide assay showed that these compounds bind to plasmid pBR322, yet weaker than distamycin. Further investigations concerning the mechanism of cytotoxicity are now in progress, but the IC(50) values suggest that synthetic distamycin analogues with a free amino group, 3-4 and 7-8, can serve as potential carriers of strong acting elements, e. g. alkylating groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Distamycins / chemical synthesis*
  • Distamycins / chemistry
  • Distamycins / pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors
  • Topoisomerase II Inhibitors

Substances

  • Antineoplastic Agents
  • Distamycins
  • Topoisomerase I Inhibitors
  • Topoisomerase II Inhibitors
  • stallimycin