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

Nadjet Rezki,El El Ashry,Salsabeel Al-Sodies,Mouslim Messali,Mohamed Aouad,Sanaa Bardaweel

doi:10.3390/ijms17050766

Abstract

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, 13C NMR, 11B, 19F, 31P 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.

Highlights

In recent years, the development of clean, safe and efficient eco-friendly protocols has become a major challenge in green chemistry
In view of the emerging importance of Ionic liquids (ILs) and hydrazones as antimicrobial and anticancer agents and our general interest in ultrasound-assisted organic synthesis, we focus on developing a straightforward, safe and ecofriendly method for the synthesis of fluorinated pyridinium ILs tethering a hydrazone linkage under ultrasound irradiation and conventional heating
Several attempts to find the optimum conditions for the synthesis of new classes of fluorinated pyridinium ionic liquid-based hydrazone have been investigated under both conventional and ultrasound methods

Summary

Introduction

The development of clean, safe and efficient eco-friendly protocols has become a major challenge in green chemistry. Ionic liquids (ILs) have emerged as fascinating new green solvents as alternatives to volatile organic solvents due to their sought-after properties such as negligible vapor pressure, high thermal stability, high ionic conductivity and high ability to solvate both polar and non-polar compounds [2,5]. Their most attractive features are their very low volatility, nonflammability and stability, which make them suitable for applications in diverse fields, such as organic synthesis, catalysis and biocatalysis, analytical chemistry, nanotechnology, food science and as function fluids (e.g., lubricants, heat transfer fluids and corrosion inhibitors) [4,5]. Some acidic task-specific ILs were used as solvents and catalysts for the hydrolysis/conversion of cellulose and lignocellulosic biomass [6]

Methods

Results

Conclusion