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.

A focused array of green imidazolium ionic liquids (ILs) encompassing benzothiazole ring and amide linkage were designed and synthesized using quaternization and metathesis protocols. The synthesized ILs have been fully characterized by usual spectroscopic methods and screened for their anticancer activities against human cancer cell lines originating from breast and colon cancers. Collectively, our biological data demonstrate that the newly synthesized series has variable anticancer activities in the examined cancer types. The synthesized ILs 8, 10 and 21-29 comprising the methyl and methyl sulfonyl benzothiazole ring emerged as the most potent compounds with promising antiproliferative activities relative to their benzothiazole ring counterparts. Furthermore, the mechanism underlying the observed anticancer activity was investigated. The most active compound 22 appears to exert its anticancer effect through apoptosis dependent pathway in breast cancer cells. Interestingly, compound 22 has also shown good in silico absorption (81.75%) along with high gastro-intestinal absorption as per ADME predictions.

Pyridinium Schiff bases and ionic liquids have attracted increasing interest in medicinal chemistry. A library of 32 cationic fluorinated pyridinium hydrazone-based amphiphiles tethering fluorinated counteranions was synthesized by alkylation of 4-fluoropyridine hydrazone with various long alkyl iodide exploiting lead quaternization and metathesis strategies. All compounds were assessed for their anticancer inhibition activity towards different cancer cell lines and the results revealed that increasing the length of the hydrophobic chain of the synthesized analogues appears to significantly enhance their anticancer activities. Substantial increase in caspase-3 activity was demonstrated upon treatment with the most potent compounds, namely 8, 28, 29 and 32 suggesting an apoptotic cellular death pathway. Quantum-polarized ligand docking studies against phosphoinositide 3-kinase α displayed that compounds 2–6 bind to the kinase site and form H-bond with S774, K802, H917 and D933.

A series of specific task ionic liquids (ILs) based on a pyridiniumhydrazone scaffold in combination with hexafluorophosphate (PF₆⁻), tetrafluoroboron (BF₄⁻) and/or trifluoroacetate (CF₃COO⁻) counter anion, were designed and characterized by IR, NMR and mass spectrometry. The reactions were conducted under both conventional and green ultrasound procedures. The antifungal potential of the synthesized compounds 2–25 was investigated against 40 strains of Candida (four standard and 36 clinical isolates). Minimum inhibitory concentrations (MIC₉₀) of the synthesized compounds were in the range of 62.5–2000 μg/mL for both standard and oral Candida isolates. MIC₉₀ results showed that the synthesized 1-(2-(4-chlorophenyl)-2-oxoethyl)-4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)-pyridin-1-ium hexafluorophosphate (11) was found to be most effective, followed by 4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)-1-(2-(4-nitrophenyl)-2-oxoethyl)-pyridin-1-ium hexafluorophosphate (14) and 1-(2-ethoxy-2-oxoethyl)-4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)pyridin-1-ium hexafluorophosphate (8). All the Candida isolates showed marked sensitivity towards the synthesized compounds. Ergosterol content was drastically reduced by more active synthesized compounds, and agreed well with MIC₉₀ values. Confocal scanning laser microscopy (CLSM) results showed that the red colored fluorescent dye enters the test agent treated cells, which confirms cell wall and cell membrane damage. The microscopy results obtained suggested membrane-located targets for the action of these synthesized compounds. It appears that the test compounds might be interacting with ergosterol in the fungal cell membranes, decreasing the membrane ergosterol content and ultimately leading to membrane disruption as visible in confocal results. The present study indicates that these synthesized compounds show significant antifungal activity against Candida which forms the basis to carry out further in vivo experiments before their clinical use.

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.

Safranine and luminol having a unique polymeric constructor combined with different nanomaterials were explored as sensors for different analytes through electrochemical and chemical techniques.