Synthesis and in vitro anticancer activity of 6,7-methylenedioxy (or 5-hydroxy-6-methoxy)-2-(substituted selenophenyl)quinolin-4-one analogs

Eur J Med Chem. 2011 Dec;46(12):6046-56. doi: 10.1016/j.ejmech.2011.10.017. Epub 2011 Oct 17.

Abstract

6,7-Methylenedioxy (or 5-hydroxy-6-methoxy)-2-(substituted selenophenyl)quinolin-4-ones and their isosteric compounds were synthesized and evaluated for anticancer activity. Structure-activity relationships (SAR) of these compounds were established. Among all tested compounds, 6,7-methylenedioxy-2-(5-methylselenophen-2-yl)quinolin-4-one (4d) was found to be the most promising anticancer agent. In screening against NCI's 60 human tumor cell line panel, 4d exhibited highly selective and potent inhibitory activity against MDA-MB-435 melanoma. Furthermore, the results of COMPARE analysis suggested that 4d is an antimitotic agent with a different mechanism of action from the conventional antimitotic agents, such as colchicine, vinca alkaloids and paclitaxel. Therefore, 4d was identified as a new lead compound that merits further optimization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Benzene Derivatives / chemical synthesis
  • Benzene Derivatives / chemistry*
  • Benzene Derivatives / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Neoplasms / drug therapy
  • Organoselenium Compounds / chemical synthesis
  • Organoselenium Compounds / chemistry*
  • Organoselenium Compounds / pharmacology*
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Benzene Derivatives
  • Organoselenium Compounds
  • Quinolines
  • benzeneselenol