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The ionic liquids are remarkable molecules with exceptional properties and applications. The microwave assisted green method was used to synthesize (yield, up to 95%) a new series of pyridinium based ionic liquids (ILs); utilizing molecular hybridization of 2- and/or 3-methyl pyridine and several fluorinated phenyls. The characterization of the synthesized ILs was carried out using different spectroscopic techniques (1H, 13C, 19F, 31P, 11B NMR and mass). The DNA binding constants (Kb) of the ionic liquids were in the range of 1.3 × 103 to 1.52 × 108 M−1; indicating good binding tendencies of the ionic liquids with DNA. All the ionic liquids intercalated with DNA through minor grooves via covalent, intercalative and electrostatic bondings. All the reported ionic liquids showed >50% anticancer activities with two lung cancer cell lines i.e. A549 and H-1229. Moreover, the maximum proliferation inhibitions were 99.16 to 91.24% for 4a series and 99.23 to 99.69% for 5a series of the ionic liquids. The docking studies indicated quite good binding affinities (−4.6 to −4.9 kcal/mol.) of the reported ionic liquids with DNA. The experimental results of DNA bindings were in good agreement with those of docking ones. The percentage inhibitions were excellent for 4a, 4e and 5n and, hence, these ionic liquids may be the future anti-cancer agents.

A focused library of new dicationic ionic liquids (DiILs) 6–41 appended pyridinium hydrazone and phenoxy side chain hybrids as counter cations were designed and synthesized, utilizing quaternization and metathesis reactions under both conventional and microwave irradiation. The novel DiILs 6–41 were fully characterized using different spectroscopic tools (1H, 13C, 19F, 11B, 31P NMR and mass spectra) and evaluated for their antimicrobial activity against diverse types of high resistant strains including two Gram-positive bacteria; methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, two Gram-negative bacteria; two Escherichia coli isolates, and Neisseria gonorrhea, and fungal strain; Candida albicans. The antibacterial screening was carried out by broth microdilution method and MIC values were reported as indicator of growth inhibition. They mostly exhibited antibacterial effect against MRSA and EC strains. The effect of the synthesized ILs on Gram-positive bacteria showed the phenoxy linker chain increases, the MIC values increases with more lethal effect due to the hydrophobicity parameter. This behavior was confirmed by the molecular dynamic simulation through the interaction with surface membrane as general mechanism of ILs. The dicationic ionic liquids are considered promising motifs for further investigations with focusing on the terminal hydrophobic adjuster.

Background Pyridinium Schiff bases and ionic liquids have attracted increasing interest in medicinal chemistry. Results 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. Conclusions 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. Electronic supplementary material The online version of this article (10.1186/s13065-018-0489-z) contains supplementary material, which is available to authorized users.

An array of dicationic pyridinium ionic liquids (DILs) based hydrazone linkage were designed and synthesized via the quaternization of the appropriate bispyridine hydrazone with different phenacyl halides and led to the formation of halogenated DILs, which undergo metathesis reaction to give the specific task dicationic pyridinium liquids carrying fluorinated counter anions (PF6−, BF4−, CF3COO−). The newly synthesized DILs were well characterized using whole spectroscopic data. The Anticancer evaluation of DILs against breast and colon cancer cell lines revealed that compound 22 appears to be the most active compound in the series with IC50 in the two-digit micromolar range. The in-vitro anticancer results were further supported by in-silico molecular docking studies revealing the highest potency of compound 22. The docking analysis demonstrated good docking score and binding affinities of the synthesized compounds on the target protein PI3Kinase.

The discovery of a novel series of task-specific fluorinated pyridinium ionic liquids (TsILs) tagged with Schiff bases is reported using ultrasound-assisted and conventional syntheses. The synthesis required the quaternization of the appropriate pyridine Schiff base, followed by the metathesis of the resulting task-specific halogenated pyridinium ILs. The structures of the ILs were established by analytical and spectral data (IR, 1H NMR, 13C NMR, 19F NMR and mass spectrometry). In vitro antimicrobial activities of the synthesized ILs on both gram-positive (Bacillus cereus, Enterococcus faecalis, and Staphylococcus aureus) and gram-negative (Proteus mirabilis, Escherichia coli, and Pseudomonas aeruginosa) bacterial strains and two fungal strains (Candida albicans and Aspergillus brasiliensis) were evaluated. Ionic liquids 8, 18, 19 and 20 appear to be the most active antimicrobials among the synthesized series. Preliminary studies were carried out to understand the relationship between the molecular structures and the inhibition activities of the synthesized ILs. In addition, the results of in silico studies revealed that all compounds exhibited good pharmacokinetic, bioavailability and toxicity profiles. Furthermore, drug likeness analysis suggests that the synthesized ILs might have appropriate oral absorption and brain penetration for application. In vivo computed LD50 values (2.59–2.78 mol/kg) were calculated for rat acute toxicity, and the compounds were found to be non-toxic and in a safe range for further study.

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.

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&ndash, 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.

Novel task dicationic ionic liquids (Ts-DiILs) 6–29 were designed and synthesized, under both conventional and microwave conditions; through molecular hybridization of the appropriate bispyridines having a hydrazone linkage as spacer with some alkyl functionalized esters forming the counter cations. Beside the synthesized halogenated DiILs 6–11, fluorinated metal anions were introduced via metathesis reaction in order to create new dipyridinium ionic liquid-hydrazone hybrids 12–29. All newly synthesized DiILs were fully characterized using different spectroscopic tools such as 1H, 13C, 19F, 31P, 11B NMR and Mass experiment. The DNA binding, anticancer and docking studies of the synthesized ionic liquids were also carried out. The DNA binding constants ranged from 4.5 × 104 to 7.2 × 104 M−1, indicating good DNA binding tendencies. The most active ionic liquids were 28 and 29 with 99.99 and 99.86% anticancer activities, respectively. The docking studies indicated DNA binding in the outer grooves of DNA. The reported ionic liquids may be used as future anticancer drugs.

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.

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.