Alkaloid-Based Isoxazolylureas: Synthesis and Effect in Combination with Anticancer Drugs on C6 Rat Glioma Model Cells

Molecules. 2024 Jul 9;29(14):3246. doi: 10.3390/molecules29143246.

Abstract

Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor activity, in combination with the commonly used five anticancer drugs, namely cyclophosphane, fluorouracil, etoposide, cisplatin, ribomustine with different mechanisms of action, was investigated. Based on the quantum chemical calculations data and molecular docking, hypotheses have been put forward to explain their mutual influence when affecting C6 rat glioma model cells.

Keywords: anabasine; antiproliferative activity; cytisine; cytotoxic activity; drug synergism; isoxazole; molecular docking; quantum chemical modeling; ureas.

MeSH terms

  • Alkaloids* / chemical synthesis
  • Alkaloids* / chemistry
  • Alkaloids* / pharmacology
  • Animals
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Glioma* / drug therapy
  • Glioma* / pathology
  • Molecular Docking Simulation*
  • Rats
  • Urea / analogs & derivatives
  • Urea / chemistry
  • Urea / pharmacology

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Urea