An Eco-Friendly Ultrasound-Assisted Synthesis of Novel Fluorinated Pyridinium Salts-Based Hydrazones and Antimicrobial and Antitumor Screening

Int J Mol Sci. 2016 May 21;17(5):766. doi: 10.3390/ijms17050766.


The present work reports an efficient synthesis of fluorinated pyridinium salts-based hydrazones under both conventional and eco-friendly ultrasound procedures. The synthetic approach first involves the preparation of halogenated pyridinium salts through the condensation of isonicotinic acid hydrazide (1) with p-fluorobenzaldehyde (2) followed by the nucleophilic alkylation of the resulting N-(4-fluorobenzylidene)isonicotinohydrazide (3) with a different alkyl iodide. The iodide counteranion of 5-10 was subjected to an anion exchange metathesis reaction in the presence of an excess of the appropriate metal salts to afford a new series of fluorinated pyridinium salts tethering a hydrazone linkage 11-40. Ultrasound irradiation led to higher yields in considerably less time than the conventional methods. The newly synthesized ILs were well-characterized with FT-IR, ¹H NMR, (13)C NMR, (11)B, (19)F, (31)P and mass spectral analyses. The ILs were also screened for their antimicrobial and antitumor activities. Within the series, the salts tethering fluorinated counter anions 11-13, 21-23, 31-33 and 36-38 were found to be more potent against all bacterial and fungal strains at MIC 4-8 µg/mL. The in vitro antiproliferative activity was also investigated against four tumor cell lines (human ductal breast epithelial tumor T47D, human breast adenocarcinoma MCF-7, human epithelial carcinoma HeLa and human epithelial colorectal adenocarcinoma Caco-2) using the MTT assay, which revealed that promising antitumor activity was exhibited by compounds 5, 12 and 14.

Keywords: anticancer activity; antimicrobial activity; hydrazones; metathesis; ultrasound irradiation.

MeSH terms

  • Anti-Infective Agents / chemical synthesis
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Bacteria / drug effects
  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Fungi / drug effects
  • Halogenation
  • HeLa Cells
  • Humans
  • Hydrazones / chemical synthesis*
  • Hydrazones / chemistry
  • Hydrazones / pharmacology
  • MCF-7 Cells
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pyridinium Compounds / chemical synthesis*
  • Pyridinium Compounds / chemistry
  • Pyridinium Compounds / pharmacology
  • Salts / chemical synthesis
  • Salts / chemistry
  • Salts / pharmacology
  • Structure-Activity Relationship
  • Ultrasonic Waves


  • Anti-Infective Agents
  • Antineoplastic Agents
  • Hydrazones
  • Pyridinium Compounds
  • Salts