Synthesis, antiproliferative activity, and mechanism of action of a series of 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides

Eur J Med Chem. 2011 Jul;46(7):2786-96. doi: 10.1016/j.ejmech.2011.03.067. Epub 2011 Apr 6.

Abstract

Several new 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides 12a-s and 17t-v were synthesized by stirring in pyridine the (E)-3-(2-R1-3-R2-4-R3-phenyl)acrylic acid chlorides 11c-k and 11t-v with the appropriate anthranilamide derivatives 10a-c or the 5-iodoanthranilic acid 13. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell line panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). COMPARE analysis, effects on tubulin polymerization in cells and with purified tubulin, and effects on cell cycle distribution for 17t, the most active of the series, indicate that these new antiproliferative compounds act as antitubulin agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylates / chemistry
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Benzamides / chemical synthesis*
  • Benzamides / pharmacology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Inhibitory Concentration 50
  • Polymerization / drug effects
  • Pyridines / chemistry
  • Structure-Activity Relationship
  • Tubulin / metabolism*
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / pharmacology
  • ortho-Aminobenzoates / chemistry

Substances

  • Acrylates
  • Antineoplastic Agents
  • Benzamides
  • Pyridines
  • Tubulin
  • Tubulin Modulators
  • ortho-Aminobenzoates
  • pyridine