Anticancer activity and SAR studies of substituted 1,4-naphthoquinones

Bioorg Med Chem. 2013 Aug 1;21(15):4662-9. doi: 10.1016/j.bmc.2013.05.017. Epub 2013 May 18.

Abstract

In this paper, we report the structure-activity relationship studies of substituted 1,4-naphthoquinones for its anticancer properties. 1,4-Naphthoquinone, Juglone, Menadione, Plumbagin and LLL12.1 were used as lead molecules to design PD compounds. Most of the PD compounds showed improved antiproliferative activity in comparison to the lead molecule in prostate (DU-145), breast (MDA-MB-231) and colon (HT-29) cancer cell lines. PD9, PD10, PD11, PD13, PD14 and PD15 were found to be the most potent compound with an IC₀ value of 1-3 μM in all cancer cell lines. Fluorescent polarization assay was employed to study the inhibition of STAT3 dimerization by PD compounds. PD9 and PD18 were found to be potent STAT3 dimerization inhibitors.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • HT29 Cells
  • Humans
  • Models, Molecular
  • Naphthoquinones / chemistry*
  • Naphthoquinones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Naphthoquinones
  • 1,4-naphthoquinone