Further naphthylcombretastatins. An investigation on the role of the naphthalene moiety

J Med Chem. 2005 Jan 27;48(2):556-68. doi: 10.1021/jm0310737.

Abstract

By synthesis and biological studies of new naphthalene analogues of combretastatins, we have found that the naphthalene is a good surrogate for the isovanillin moiety (3-hydroxy-4-methoxyphenyl) of combretastatin A-4, always generating highly cytotoxic analogues when combined with the 3,4,5-trimethoxyphenyl or related systems. On the other hand, when the naphthalene replaces the 3,4,5-trimethoxyphenyl moiety, the cytotoxic activity is largely decreased. The most cytotoxic naphthalene analogues of combretastatins, which also produce inhibition of tubulin polymerization, exerted their antimitotic effects through microtubule network disruption and subsequent G(2)/M arrest of the cell cycle in human cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemical synthesis*
  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Biopolymers
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Humans
  • Microtubules / drug effects
  • Microtubules / ultrastructure
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Stereoisomerism
  • Stilbenes / chemical synthesis*
  • Stilbenes / chemistry
  • Stilbenes / pharmacology
  • Structure-Activity Relationship
  • Tubulin / chemistry

Substances

  • Aniline Compounds
  • Antineoplastic Agents
  • Biopolymers
  • N,N-dimethyl-2-amino-4-(2-(3,4,5-trimethoxyphenyl)vinyl)aniline
  • Naphthalenes
  • Stilbenes
  • Tubulin
  • fosbretabulin