Design, Synthesis, and Apoptosis-Promoting Effect Evaluation of Chalcone Derivatives Containing Aminoguanidine Units

Anticancer Agents Med Chem. 2022;22(11):2116-2124. doi: 10.2174/1871520621666211026091226.

Abstract

Background: Chalcones are precursors of flavonoids or isoflavonoids, and they are abundant in edible plants. Chalcones constitute an important group of natural and synthetic products with a wide range of pharmacological activities.

Objective: To determine the seeds of the anti-tumor agents, we focused on the potential bioactive materials obtained from chalcone derivatives.

Methods: Two series of chalcone derivatives containing aminoguanidine or bis-chalone were designed, synthesized, and screened for their cytotoxicity, proliferation inhibition, and apoptosis-promoting activity in vitro against a panel of human tumor cell lines.

Results: Among the various compounds studied in this work, 2-((E)-4-((E)-3-oxo-3-(p-tolyl)prop-1-en-1- yl)benzylidene)hydrazine-1-carboximidamide (5f) was the most potent, with IC50 values of 7.17 μM and 3.05 μM antiproliferative activity in vitro against human hepatocarcinoma HepG2 cells and SMMC-7721 cells, respectively. This result showed that the compound possessed a certain degree of selectivity for human hepatocarcinoma cells, especially for SMMC-7721. Then, Annexin V/PI flow cytometry assay was used to investigate different concentrations of compound 5f to demonstrate the ability of compound 5f in inducing apoptosis of SMMC-7721 cells in a concentrationdependent manner. Finally, these results were further verified by Western blot analysis.

Conclusion: Based on the collective results, compound 5f may be a promising anti-cancer compound, and may play a significant role in subsequent research.

Keywords: Synthesis; aminoguanidine; anticancer; apoptosis; chalcone; derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Chalcone* / pharmacology
  • Chalcones* / pharmacology
  • Drug Screening Assays, Antitumor
  • Guanidines
  • Humans
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Chalcones
  • Guanidines
  • Chalcone
  • pimagedine