New pyrazole-tetrazole hybrid compounds as potent α-amylase and non-enzymatic glycation inhibitors.

The synthesis of eight novel pyrazole-tetrazole compounds are presented. Their structures are identified by NMR and FTIR spectroscopy, mass spectrometry as well as elemental analysis. Their in-vitro α-amylase inhibition and haemoglobin antiglycation activity were examined by spectrophotometric methods. All compounds possess both activities, especially molecules entitled 2-(1-((5-methyl-1H-pyrazol-3-yl)methyl)-1H-tetrazol-5-yl)pyridine 4 and 2-(1-((1-ethyl-5-methyl-1H-pyrazol-3-yl)methyl)-1H-tetrazol-5-yl)pyridine 8 which were found to be extremely potent compared to the positive controls. The SAR study proved the influence of the alkylation position of pyrazole derivative on the tetrazole ring, the nature of substituent on the tetrazolic carbon atom and the nature of the group at the nitrogen atom of the pyrazole ring on both α-amylase and glycation inhibition activity. Compounds 4 and 8 could be a good drug candidate to treat Type 2 diabetes.

Insights on the Synthesis of N-Heterocycles Containing Macrocycles and Their Complexion and Biological Properties.

Macrocyclic chemistry has been extensively developed over the past several decades. In fact, the architecture of new macrocyclic models has undergone exponential growth to offer molecules with specific properties. In this context, an attempt is made in this study to provide an overview of some synthetic methods allowing the elaboration of N-heterocycles containing macrocycles (imidazole, triazole, tetrazole, and pyrazole), as well as their applications in the complexation of metal cations or as pharmacological agents.

Substituent Effects in 3,3' Bipyrazole Derivatives. X-ray Crystal Structures, Molecular Properties and {DFT} Analysis.

The single crystal X-ray structure of new 1,1'-bis(2-nitrophenyl)-5,5'-diisopropyl-3,3'-bipyrazole, 1, is triclinic P , a = 7.7113(8), b = 12.3926(14), c = 12.9886(12) Å, a = 92.008(8), ß = 102.251(8), γ = 99.655(9)°. The structural arrangement is compared to that of 5,5'-diisopropyl-3,3'-bipyrazole, 5, whose single crystal structure is found tetragonal I41/a, a = b = 11.684(1), c = 19.158(1) Å. The comparison is also extended to the structures previously determined for 1,1'-bis(2-nitrophenyl)-5,5'-propyl-3,3'-bipyrazole, 2, 1,1'-bis(4-nitrophenyl)-5,5'-diisopropyl-3,3'-bipyrazole, 3, and 1,1'-bis(benzyl)-5,5'-diisopropyl-3,3'-bipyrazole, 4. Density Functional Theory (DFT) calculations are used to investigate the molecular geometries and to determine the global reactivity parameters. The geometry of isolated molecules and the molecular arrangements in the solid state are analyzed according to the nature of the groups connected to the bipyrazole core.

Synthesis and characterization of new pyrazole-tetrazole derivatives as new vasorelaxant agents.

The synthesis of new functionalized tetrazole-pyrazole compounds is reported. They were fully characterized by spectroscopy and spectrometry methods. The vasorelaxant potency of these molecules was also investigated. All compounds showed a good vasorelaxant activity but the Compound 6 "ethyl 1-((2-(3-bromopropyl)-2H-tetrazol-5-yl)methyl)-5-methyl-1H-pyrazole-3-carboxylate" seems to have the highest effect, which reached 70% at 10-4  M concentration. This effect was partially endothelium-dependent; also, the vasorelaxant pattern of this compound was quite similar to that of the verapamil.

Synthesis, Characterization, Antimicrobial Activity, and Docking Studies of New Triazolic Tripodal Ligands.

The synthesis and characterization of new N-donor bitriazolic tripods were reported. The in vitro antibacterial and antifungal activities of these products were screened against fungal strain (Candida pelliculosa) and against four bacterial strains (Micrococcus luteus, Bacillus subtilis, Listeria innocua, and Escherichia coli). Biological data revealed the effect of the chemical structure on antimicrobial activity. Molecular docking studies of some compounds showed that they could act as inhibitors for the biotin carboxylase enzyme.

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 (IC(50)) was more pronounced against P815 cell line (IC(50): 39.42 microg mL(-1) for the compound 1 and 97.74 microg mL(-1) for the compound 2) than the Hep cell line (IC(50): 83.49 microg mL(-1) for compound 1 and 185.30 microg 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.