Total synthesis and anti-tubulin activity of epi-c3 analogues of cryptophycin-24

J Med Chem. 2004 Jul 1;47(14):3697-9. doi: 10.1021/jm030555f.

Abstract

Epi-C3-cryptophycin-24, epi-C3-m-chlorobenzyl-cryptophycin-24, and the corresponding styrenes were synthesized and tested in vitro against the MCF-7 and multidrug-resistant MCF-7/ADR breast cancer cell lines and in an in vitro tubulin assembly assay. The results demonstrate that the S configuration at the C3 stereocenter is not required to induce potent cytotoxicity and the m-Cl substituent present on the C10 side chain did not induce any large change in activity.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Biopolymers
  • Cell Line, Tumor
  • Depsipeptides*
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Humans
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Styrenes / chemical synthesis
  • Styrenes / chemistry
  • Styrenes / pharmacology
  • Tubulin / chemistry*

Substances

  • Antineoplastic Agents
  • Biopolymers
  • Depsipeptides
  • Peptides, Cyclic
  • Styrenes
  • Tubulin
  • arenastatin A