Novel Dipyridinium Lipophile-Based Ionic Liquids Tethering Hydrazone Linkage: Design, Synthesis and Antitumorigenic Study.

Salsabeel Al-Sodies,Nadjet Rezki,Mouslim Messali,Sanaa K Bardaweel,Mohamed Hagar,Fawzia Faleh Albelwi,Mohamed R Aouad

doi:10.3390/ijms221910487

Abstract

Novel dicationic pyridinium ionic liquids tethering amphiphilic long alkyl side chains and fluorinated counter anions have been successfully synthesized by means of the quaternization of the dipyridinium hydrazone through its alkylation with different alkyl halides. The resulting halogenated di-ionic liquids underwent a metathesis reaction in order to incorporate some fluorinated counter anions in their structures. The structures of all the resulting di-ionic liquids were characterized by several spectroscopic experiments. The antitumorigenic activities of the investigated compounds were further studied against three different human lung cancer cell lines. Compared to the standard chemotherapeutic agent, cisplatin, the synthesized di-ionic liquids exerted equal, even more active, moderate, or weak anticancer activities against the various lung cancer cell lines under investigation. The observed anticancer activity appears to be enhanced by increasing the length of the aliphatic side chains. Moreover, dicationic pyridinium bearing a nine carbon chain as counter cation and hexafluoro phosphate and/or tetrafluoro bororate as counter anion were selected for further evaluation and demonstrated effective and significant antimetastatic effects and suppressed the colonization ability of the lung cancer cells, suggesting a therapeutic potential for the synthesized compounds in lung cancer treatment.

Highlights

IntroductionEffective treatments for lung cancer vary depending on the histologic type of cancer, the clinical stage, and the patient’s functional status [4]
We proposed to construct a library of dipyridinium ionic liquids tethering numerous long alkyl side chains and some fluorinated anions and test them for antitumorigenic
The dipyridinium hydrazone 1 was selected as the starting material for the synthesis of the designed DiILs

Summary

Introduction

Effective treatments for lung cancer vary depending on the histologic type of cancer, the clinical stage, and the patient’s functional status [4]. Radiotherapy, targeted therapy, chemotherapy, and immunotherapy are common effective treatments, with clear limitations for each type of therapy and high tumor relapse rates among patients [5]. While surgery is the first line treatment option in the early stages of lung cancers, it is not effective when metastasis to other organs occurs [4]. Lung cancer patients have a five-year survival rate of less than 20% throughout all stages [1,2]. It is crucial to examine new, safe, and effective therapeutic options against lung cancer

Results

Discussion

Conclusion