2-Thienyl-4-furyl-6-aryl pyridine derivatives: synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study

Bioorg Med Chem. 2010 Jan 1;18(1):377-86. doi: 10.1016/j.bmc.2009.10.049. Epub 2009 Oct 29.

Abstract

Designed and synthesized 60 2-thienyl-4-furyl-6-aryl pyridine derivatives were evaluated for their topoisomerase I and II inhibitory activities at 20 microM and 100 microM and cytotoxicity against several human cancer cell lines. Compounds 8, 9, 11-29 showed significant topoisomerase II inhibitory activity and compounds 10 and 11 showed significant topoisomerase I inhibitory activity. Most of the compounds (7-21) possessing 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl) moiety showed higher or similar cytotoxicity against HCT15 cell line as compared to standards. Most of the selected compounds displayed moderate cytotoxicity against MCF-7, HeLa, DU145, and K562 cell lines. Structure-activity relationship study revealed that 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl) moiety has an important role in displaying biological activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Topoisomerases, Type I / metabolism
  • DNA Topoisomerases, Type II / metabolism
  • Drug Screening Assays, Antitumor
  • Humans
  • Inhibitory Concentration 50
  • Neoplasms / drug therapy
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*
  • Topoisomerase II Inhibitors*

Substances

  • Antineoplastic Agents
  • Pyrimidines
  • Topoisomerase I Inhibitors
  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type I
  • DNA Topoisomerases, Type II