New 1H-Benzo[f]indazole-4,9-diones Conjugated with C-Protected Amino Acids and Other Derivatives: Synthesis and in Vitro Antiproliferative Evaluation

Molecules. 2015 Dec 8;20(12):21924-38. doi: 10.3390/molecules201219809.

Abstract

1H-Benzo[f]indazole-4,9-dione derivatives conjugated with C-protected amino acids (glycine, l-alanine, l-phenylalanine and l-glutamic acid) 6a-l were prepared by chemically modifying the prenyl substituent of 3-methyl-7-(4-methylpent-3-enyl)-1H-benzo[f]indazole-4,9-dione 2 through epoxidation, degradative oxidation, oxidation and N-acyl condensation reactions. The chemical structures of the synthesized compounds were elucidated by analyzing their IR, ¹H-NMR and (13)C-NMR spectral data together with elemental analysis for carbon, hydrogen and nitrogen. The preliminary in vitro antiproliferative activity of the synthesized derivatives was evaluated on KATO-III and MCF-7 cell lines using a cell proliferation assay. The majority of the derivatives exhibited significant antiproliferative activity with IC50 values ranging from 25.5 to 432.5 μM. These results suggest that 1H-benzo[f]indazole-4,9-dione derivatives are promising molecules to be researched for developing new anticancer agents.

Keywords: 1,4-naphthoquinone; 1H-benzoindazole; amino acid; pyrazole.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Cell Proliferation / drug effects*
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • In Vitro Techniques
  • Indazoles / chemistry*
  • Molecular Structure
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / pathology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Amino Acids
  • Antineoplastic Agents
  • Indazoles