Unsymmetrically Substituted Dibenzo[ b,f][1,5]-diazocine-6,12(5 H,11 H)dione-A Convenient Scaffold for Bioactive Molecule Design

Molecules. 2020 Feb 18;25(4):906. doi: 10.3390/molecules25040906.

Abstract

A novel approach for the synthesis of unsymmetrically substituted dibenzo[b,f][1,5]diazocine-6,12(5H,11H)diones has been developed. This facile three-step method uses variously substituted 1H-benzo[d][1,3]oxazine-2,4-diones (isatoic anhydrides) and 2-aminobenzoic acids as a starting materials. The obtained products were further transformed into N-alkyl-, N-acetyl- and dithio analogues. Developed procedures allowed the synthesis of unsymmetrical dibenzo[b,f][1,5]diazocine-6,12(5H,11H)diones and three novel heterocyclic scaffolds: benzo[b]naphtho[2,3-f][1,5]diazocine-6,14(5H,13H)dione, pyrido[3,2-c][1,5]benzodiazocine-5,11(6H,12H)-dione and pyrazino[3,2-c][1,5]benzodiazocine-6,12(5H,11H)dione. For 11 of the compounds crystal structures were obtained. The preliminary cytotoxic effect against two cancer (HeLa, U87) and two normal lines (HEK293, EUFA30) as well as antibacterial activity were determined. The obtained dibenzo[b,f][1,5]diazocine(5H,11H)6,12-dione framework could serve as a privileged structure for the drug design and development.

Keywords: crystallographic analysis; cytotoxicity; heterocycles; isatoic anhydrides; unsymmetrical dibenzo[b,f][1,5]diazocines.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Azocines / chemical synthesis
  • Azocines / chemistry*
  • Benzene / chemical synthesis
  • Benzene / chemistry*
  • Cell Death
  • Crystallography, X-Ray
  • Cyclization
  • Drug Design*
  • Flow Cytometry
  • HEK293 Cells
  • HeLa Cells
  • Humans

Substances

  • Anti-Bacterial Agents
  • Azocines
  • Benzene