Nadjet Rezki

Synthesis of Novel 2,5-Disubstituted-1,3,4-thiadiazoles Clubbed 1,2,4-Triazole, 1,3,4-Thiadiazole, 1,3,4-Oxadiazole and/or Schiff Base as Potential Antimicrobial and Antiproliferative Agents

In the present study, a new series of 2,5-disubstituted-1,3,4-thiadiazole tethered 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole and Schiff base derivatives were synthesized and characterized by IR, 1H-NMR, 13C-NMR, MS and elemental analyses. All compounds were screened for their antibacterial, antifungal and antiproliferative activity. Some of the synthesized derivatives have displayed promising biological activity.

Synthesis, characterization, and POM analysis of novel bioactive imidazolium-based ionic liquids

An efficient green ultrasound-assisted procedure for the preparation of five new functionalized 1-alkyl-3-butylimidazolium ionic liquids (ILs) 2–6 is described. Their structures were characterized by FT-IR, 1H NMR, and 13C NMR spectroscopy and mass spectrometry. The newly synthesized compounds were screened for their antimicrobial and anticancer activities. The former revealed that the ILs exhibited promising activity compared with standard drugs. Moreover, IL 4 was found to be a very promising antiproliferative agent against the human hepatocellular carcinoma (HEPG2), human breast adenocarcinoma (MCF7), and colon carcinoma (HCT116) cell lines and consistently produced low IC50 values.

A Green Ultrasound Synthesis, Characterization and Antibacterial Evaluation of 1,4-Disubstituted 1,2,3-Triazoles Tethering Bioactive Benzothiazole Nucleus

The synthesis of N-(benzo[d]thiazol-2-yl)-2-(4-substituted-1H-1,2,3-triazol-1-yl)acetamides 5a–r via the 1,3-dipolar cycloaddition reaction between 2-azido-N-(benzo[d]thiazol-2-yl)acetamide derivatives 3a–c and different alkynes were performed in the presence and absence of ultrasound irradiation. The synthesis was carried out using t-BuOH/H2O (1:1, v/v) as reaction solvents and CuSO4·5H2O/sodium ascorbate as the catalyst. The copper catalyst was implemented to provide the regioselective 1,4-disubstituted 1,2,3-triazoles 5a–r. Significant reductions in reaction times with comparably higher yields were observed when the reactions were carried out under ultrasound irradiation. The structures of the newly synthesized 1,2,3-triazoles were elucidated by IR, NMR, MS, and elemental analyses. They were also screened for their antimicrobial activity against three gram-positive (Streptococcus pneumonia, Bacillus subtilis, and Staphylococcus aureus), three gram-negative (Pseudomonas aeuroginosa, Escherichia coli, and Klebsiella pneumonia), and two fungal strains (Aspergillus fumigates and Candida albicans). Most of the tested compounds displayed promising antimicrobial activities at a Minimum Inhibition Concentration (MIC) of 4–16 μg/mL.

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

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.

Synthesis and Characterization of a New Five and Six Membered Selenoheterocyclic Compounds Homologues of Ebselen

The discovery of the antioxidant activity of selenoenzyme glutathione peroxidase (GPx) has attracted growing attention in the biochemistry of selenium. Among molecules which mimic the structure of the active site of the enzyme, N-phenyl-1,2-benzisoselenazolin-3-one 1, Ebselen, exhibited useful anti-inflammatory properties. It has been extensively investigated and has undergone clinical trials as an anti-inflammatory agent. Unfortunately, Ebselen exhibits relatively poor catalytic activity, prompting attempts to design more efficacious GPx mimetics that would retain his low toxicity while manifesting improved catalytic properties. In this context, novel 1,2-benzoselenazine and 1,2-benzoselenazols, which are five and six membered homologues of Ebselen were synthesized and characterized. One structure has been proven by single crystal X-ray crystallography.

Green Ultrasound versus Conventional Synthesis and Characterization of Specific Task Pyridinium Ionic Liquid Hydrazones Tethering Fluorinated Counter Anions: Novel Inhibitors of Fungal Ergosterol Biosynthesis

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.

Preparation of Novel 3-Fluorophenyl Triazolothiadiazoles and of Triazolothiadiazines

Mohamed R. Aouad, Amr M. Hassan Al-Saedi, Adeeb A. Ali, Nadjet Rezki, and Mouslim Messali Department of Chemistry, Faculty of Sciences, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia Laboratoire de Chimie & Electrochimie des Complexes M etalliques (LCECM) USTO-MB, Department of Chemistry, Faculty of Sciences, University of Sciences and Technology Mohamed Boudiaf, B.p. 1505 El M’nouar, Oran 31000, Algeria

Click 1,4-regioselective synthesis, characterization, and antimicrobial screening of novel 1,2,3-triazoles tethering fluorinated 1,2,4-triazole and lipophilic side chain

Base-catalyzed alkylation of 5-(4-fluorophenyl)-2,4-dihydro-1,2,4-triazole-3-thione (3) with one or two equivalents of propargyl bromide in presence of triethylamine as catalyst selectively produced the thiopropargylated 1,2,4-triazole 7 in 90xa0% yield. Under the same reaction conditions, 4-ethyl-5-(4-fluorophenyl)-3-(prop-2-yn-1-ylthio)-1,2,4-triazole (8) was produced. Conversely, when the propargylation was carried out in presence of sodium bicarbonate, a mixture of S,N4- (24) and S,N2-bis(propargylated) triazoles (25) was obtained in 85xa0% overall yield. The click 1,3-dipolar cycloaddition reaction of the mono- (7, 8) and/or bis(propargylated)-1,2,4-triazoles (24) with a variety of long-chain alkyl azides, conducted in t-BuOH:H2O (10:1) in presence of sodium ascorbate and copper(II) sulfate at room temperature, afforded the regioselective 1,4-disubstituted mono- (14–18) and bis(1,2,3-triazole) derivatives (26–30) containing a fluorinated 1,2,4-triazole moiety and a lipophilic side chain. The structures of the new products were elucidated by infrared (IR), 1H and 13C nuclear magnetic resonance (NMR), and mass spectrometry. They were also assessed inxa0vitro for their antimicrobial potency against six bacteria (Bacillus subtilis, Streptococcus pneumonia, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumonia) and two fungi (Aspergillus fumigatus and Candida albicans). The bioassay results revealed that some of the tested compounds displayed promising antimicrobial activity.

Design, synthesis, in silico and in vitro antimicrobial screenings of novel 1,2,4-triazoles carrying 1,2,3-triazole scaffold with lipophilic side chain tether

Background1,2,4-Triazoles and 1,2,3-triazoles have gained significant importance in medicinal chemistry.ResultsThis study describes a green, efficient and quick solvent free click synthesis of new 1,2,3-triazole-4,5-diesters carrying a lipophilic side chain via 1,3-dipolar cycloaddition of diethylacetylene dicarboxylate with different surfactant azides. Further structural modifications of the resulting 1,2,3-triazole diesters to their corresponding 1,2,4-triazole-3-thiones via multi-step synthesis has been also investigated. The structures of the newly designed triazoles have been elucidated based on their analytical and spectral data. These compounds were evaluated for their antimicrobial activities. Relative to the standard antimicrobial agents, derivatives of 1,2,3-triazole-bis-4-amino-1,2,4-triazole-3-thiones were the most potent antimicrobial agents with compound 7d demonstrating comparable antibacterial and antifungal activities against all tested microorganisms. Further, the selected compounds were studied for docking using the enzyme, Glucosamine-6-phosphate synthase.ConclusionsThe in silico study reveals that all the synthesized compounds had shown good binding energy toward the target protein ranging from −xa010.49 to −xa05.72xa0kJxa0mol−1 and have good affinity toward the active pocket, thus, they may be considered as good inhibitors of GlcN-6-P synthase.

Crystal structure of 4-(dimethylamino)-1-(prop-2-yn-1-yl)pyridin-1-ium perchlorate, C10H13ClN2O4

Abstract C10H13ClN2O4, orthorhombic, Pnma, a = 14.903(2) Å, b = 9.1004(15) Å, c = 8.7560(14) Å, V = 1187.5(3) Å3, Z = 4, Rint = 0.036, Rgt(F) = 0.0284, wRref(F2) = 0.0795, T = 296 K.