An Efficient Synthetic Approach Towards Benzo[ b]pyrano[2,3- e][1,4]diazepines, and Their Cytotoxic Activity

Molecules. 2020 Apr 28;25(9):2051. doi: 10.3390/molecules25092051.

Abstract

In search of unprecedented tri and/or tetrapod pharmacophoric conjugates, a series of 32 new 4-ethyl-1H-benzo[b][1,4]diazepin-2(3H)-ones were synthesized and properly elucidated using MS, IR, NMR, and elemental analysis. In vitro investigation of 11 compounds of this series, using a panel of two human tumor cell lines namely; human breast adenocarcinoma (MCF-7), and human colorectal carcinoma (HCT-116), revealed promising cytotoxic activities. Among all synthesized compounds, analogue 9 displayed maximum cytotoxicity with IC50 values of 16.19 ± 1.35 and 17.16 ± 1.54 μM against HCT-116 and MCF-7, respectively, compared to standard drug doxorubicin.

Keywords: N-heterocycles; benzodiazepine; cyclocondensation reaction; cytotoxic activity.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Benzodiazepines / chemical synthesis*
  • Benzodiazepines / pharmacology*
  • Cell Line, Tumor
  • Chemistry Techniques, Synthetic
  • Chemistry, Pharmaceutical / methods*
  • Doxorubicin / pharmacology
  • Drug Design*
  • Drug Screening Assays, Antitumor*
  • HCT116 Cells
  • Humans
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Spectrophotometry, Infrared

Substances

  • Antineoplastic Agents
  • Benzodiazepines
  • Doxorubicin