Synthesis and structure-activity relationships of 2-amino-1-aroylnaphthalene and 2-hydroxy-1-aroylnaphthalenes as potent antitubulin agents

J Med Chem. 2008 Dec 25;51(24):8163-7. doi: 10.1021/jm8008635.

Abstract

A series of aroylnaphthalene derivatives were prepared as bioisosteres of combrestatin A-4 and evaluated for anticancer activity. 2-Amino-1-aroylnaphthalene and 2-hydroxy-1-aroylnaphthalene, 9 and 8, respectively, showed strong antiproliferative activity with IC(50) values of 2.1-26.3 nM against a panel of human cancer cell lines including multiple-drug resistant cell line. Compound 9 demonstrated better antiproliferative activity and has a comparable tubulin binding efficacy as that of colchicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anisoles / chemical synthesis*
  • Anisoles / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Humans
  • Indoles / chemistry
  • Inhibitory Concentration 50
  • Models, Chemical
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Neoplasms / drug therapy*
  • Structure-Activity Relationship
  • Tubulin / chemistry*
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / pharmacology

Substances

  • Anisoles
  • Indoles
  • Naphthalenes
  • Tubulin
  • Tubulin Modulators
  • naphthalene