Rachid Touzani

2,3-Bifunctionalized Quinoxalines: Synthesis, DNA Interactions and Evaluation of Anticancer, Anti-tuberculosis and Antifungal Activity

A variety of 2,3-bifunctionalized quinoxalines (6-14) have been prepared by the condensation of 1,6-disubstituted-hexan-1,3,4,6-tetraones (1-4) with o-phenylenediamine, (R,R)-1,2-diaminocyclohexane and p-nitro-o-phenylenediamine. It is concluded that strong intramolecular N-H----O bonds in the favoured keto-enamine form may be responsible for the minimal biological activities observed in DNA footprinting, anti-tubercular, anti-fungal and anticancer tests with these hyper π-conjugated quinoxaline derivatives. However, subtle alteration by addition of a nitro group affecting the charge distribution confers significant improvements in biological effects and binding to DNA.

Corrosion inhibition of copper in 3 per cent NaCl solution by new bipyrazolic derivatives

The inhibition of the copper corrosion in aerated 3 per cent sodium chloride solution was studied by using electrochemical polarisation, weight loss and impedance measurements in the presence of different concentration of synthesised bipyrazolic compounds: N,N‐bis (3,5‐dimethylpyrazol‐1‐ylmethyl) butylamine (bipy1); N,N‐bis (3,5‐dimethylpyrazol‐1‐ylmethyl) allylamine (bipy2); N,N‐bis (3,5‐dimethylpyrazol‐1‐ylmethyl) ethanolamine. (bipy3); N,N‐bis (3,5‐dimethylpyrazol‐1‐ylmethyl) cyclohexylamine (bipy4); N,N‐bis (3‐carbomethoxy‐5‐methylpyrazol‐1‐ylmethyl) cyclohexylamine (bipy5); N,N‐bis(3‐carboethoxy‐5‐methylpyrazol‐1‐ylmethyl) cyclohexylamine (bipy6). The inhibition efficiencies obtained from cathodic Tafel plots, polarisation resistance and weight loss are in good agreement with electrochemical impedance spectroscopy (EIS) measurements. All these additives were found to be excellent inhibitors of copper corrosion. The difference in inhibition efficiencies of these inhibitors was not big, but the optimum...

New bipyrazole derivatives as effective inhibitors for the corrosion of mild steel in 1M HCI medium

The inhibition of the corrosion of the mild steel in 1M HCl by new bipyrazolic compounds has been studied by weight loss, electrochemical polarisation and electrochemical impedance spectroscopy (EIS) measurements. Results obtained reveal that these compounds are very good inhibitors. The inhibition efficiency increases with the increase of inhibitor concentration and reached 94 at 10–3M for the bipyrazoles studied. Potentiodynamic polarisation studies clearly reveal that the presence of the bipyrazoles does not change the mechanism of the hydrogen evolution reaction and they act essentially as cathodic inhibitors. The effect of temperature on the corrosion behaviour of mild steel in 1M HCl without and with the bipyrazoles at 10–3M was studied in the temperature range from 298° to 343°K. EIS measurements show the increase of the transfer resistance with the inhibitor concentration.

EFFICIENT SYNTHESIS OF NEW NITROGEN DONOR CONTAINING TRIPODS UNDER MICROWAVE IRRADIATION AND WITHOUT SOLVENT

Five new N,N-bis(pyrazole-1-yl-methyl) alkylamines have been prepared in one step by condensation of two equivalents of 1-(hydroxymethyl)-3,5-disubstituted pyrazoles with a series of primary amines. This reaction is carried out under microwave irradiation (60 W) in the absence of solvent for 20 m and affords high yields (75–90%) of mixed nitrogen donor tripodal molecules.

New azole antifungal agents with novel modes of action: synthesis and biological studies of new tridentate ligands based on pyrazole and triazole.

The synthesis and extensive biological study of two new tridentates ligands based on pyrazole and triazole are described. The antifungal activity against the budding yeast cells of the newly synthesized compounds was determined. These compounds were toxic to yeast cells. Cell cycle analysis suggested that treatment with these compounds impairs cell division in G1 of the cell cycle. Using yeast-based functional genomics technologies, we found that these compounds tolerance requires DNA repair pathway and SKI complex function. We have also found that the PKC1 heterozygous deletion strain was the most sensitive to these compounds using HaploInsufficiency Profiling, suggesting that the Pkc1 protein may be the target for these compounds. These results strongly suggest that these compounds induce DNA damage and thus exert a different mechanism of action compared to other azole derivatives. These two compounds might therefore represent promising lead compounds for further development of antifungal drugs for human therapy.

Synthesis and X-Ray Structure of (N,N-Bis(3,5-dimethylpyrazol- 1-ylmethyl)-1-hydroxy-2-aminoethane)(3,5-dimethylpyrazole) copper(II) dinitrate

The tridentate ligand N,N-Bis(3,5-dimethylpyrazol-1-ylmethyl)-1-hydroxy-2-aminoethane (L) has been prepared in one step by condensation of two equivalents of 1-hydroxymethyl-3,5-dimethylpyrazole with one equivalent of 2-aminoethanol. This reaction is carried out under microwave irradiation (60 W) in the absence of solvent for 20 min [1]. Using this ligand L a new Cu(II) dinitrate complex has been prepared. The single-crystal X-ray structure of the title compound, [N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)-1-hydroxy-2-aminoethane] (3,5-dimethylpyrazole)copper(II) dinitrate, revels that the copper (II) ion is coordinated to two pyrazole nitrogens, one tertiary amine nitrogen of the ligand L and 3,5-dimethylpyrazole, and in the apical position by an alcohol O atom.

New synthesis of two tridentate bipyrazolic compounds and their cytotoxic activity tumor cell lines

Two new tripodal compounds—4-{bis[(3,5-dimethyl-1H-pyrazole-1-yl)methyl]amino}butane-1-ol (1); ethyl 1-[((2-hydroxyethyl){[3-(ethoxycarbonyl)-5-methyl-1H-pyrazole-1-yl]methyl} amino)methyl]-5-methyl-1H-pyrazole-3-carboxylate (2) were reported. The evaluation of the cytotoxic properties in vitro of these ligands, was examined on two tumor cell lines—P815 (mastocytome murine) and Hep (carcinoma of human larynx). The concentration required to induce 50% of lysis (IC50) was more pronounced against P815 cell line (IC50: 39.42 µg mL−1 for the compound 1 and 97.74 µg mL−1 for the compound 2) than the Hep cell line (IC50: 83.49 µg mL−1 for compound 1 and 185.30 µg mL−1 for compound 2). Statistical analysis shows that the compound 1 is two to three folds more cytotoxic than the compound 2 (p < 0.05). Interestingly, the cytotoxic activity depends strongly on both the substituents linked to the aminic nitrogen and pyrazolic rings.

Pyrazole Derivatives with NCN Junction and their Biological Activity: AReview

Pyrazole derivatives have their own importance in aromatic organic heterocycle family. Application of these derivatives in chemistry and biology has attracted increasing interest occupy a unique place in field of medicinal chemistry due to their wide spectrum of biological activities. There are known for their anticancer, antiviral, antibacterial, antifungal, analgesic and anti-inflammatory and activities and so on. Due to the importance of this chemical skeletons, the present review reports the recent progress (2010-2016) on the biological activities of some monodentate, bidentate, tridentate and tetradente compounds based on pyrazole moieties and containing NCN bonds which connecting between the pyrazole and amine unit.

Effect of Two Isomeric Tetrapyrazolyl Ligands on the Catalytic Oxidation of 3,5-di- tert -Butylcatechol

Copper(II) salts were combined with a tetrapyrazolyl ligand ({N,N,N’,N’-tetrakis-[(3,5-dimethylpyrazol-1-yl)methyl)-1,4-phenylenediamine}L1 or {N,N,N’,N’-tetrakis-[(1,5-dimethylpyrazol-3-yl)methyl)-1,4-phenylenediamine}L2) and assessed as oxidation catalysts. The corresponding dioxygen complexes were generated in situ by mixing the copper salt and the pyrazolyl donor ligand in air. The oxidation of 3,5-di-tert-butylcatechol (DTBC), which affords 3,5-di-tert-butylquinone (DTBQ), was studied. The reaction rate was found to depend essentially on the nature of the junction linking two pyrazolyl neighbours.

Synthesis, Characterization by Means of IR, 1H, 13C - NMR and Biological Investigations on New Diorganotin Carboxylic Acid Derivatives

Abstract: New organotin (IV) based on 2-(thiophene-2-yl)acetic acid and 1-H-pyrazole-3-carboxylic acid derivatives 1a-e and 2a-e was prepared and characterized by IR, 1 H and 13 C NMR spectroscopy. These reactions were carried out under refluxing conditions using CHCl 3 / EtOH (3:1) as solvents and 2:1 / 1:1 acid / metal oxide rations. The tin products were recuperated with moderate and good yields (55-85%). The Compounds ( 1b , 1e and 2e ) were screened for their antitumor activities against two human tumor cell lines: HeLa , an epithelial cell from a fatal cervical carcinoma and HEK293 , an embryonic kidney tumor. All three materials show an activity in vitro against these cell lines. Keywords: Synthesis, Tin, Carboxylic acids, Antitumor activities. 1. INTRODUCTION During the later part of the 20 th century, pharmaceutical compounds containing metals began to play an increasingly important role in medicine. In particular, the discovery of platinum anticancer drugs and the appearance of organ spe-cific diagnostic-imaging agents containing technetium were prominent developments that have stimulated further interest in so-called ‘metallopharmaceuticals’. Today, the metallo-pharmaceuticals industry has a global market measured in billions of dollars and has well established applications in both diagnostic and therapeutic medicine [1]. Meanwhile, the neurotoxicity of trialkyl tin derivatives is well known and various organotin compounds have been assessed in search for anticancer activity. Studies of alkyl or aryl tin benzoate derivatives showed compounds of the type [SnR