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.

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.

Myorelaxant and antispasmodic effects of the essential oil of Artemisia campestris L., and the molecular docking of its major constituents with the muscarinic receptor and the L-type voltage-gated Ca2+channel.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrointestinal disorders are among the most common diseases that cause discomfort to people who are affected. In Morocco, aromatic and medicinal plants are widely used to calm these pains and eliminate their symptoms. Among these plants, Artemisia campestris L. which is used in eastern Morocco to treat digestive system problems. AIM OF THE STUDY: Our study aimed to experimentally verify the traditional use of this plant by evaluating the myorelaxant and antispasmodic effects of the essential oil of Artemisia campestris L. (EOAc). MATERIALS AND METHODS: Gas Chromatography-Mass Spectrometry analysis (GC-MS) was performed to identify the compounds present in the EOAc. Then, these molecules were subjected to the in silico study for molecular docking. The myorelaxant and antispasmodic evaluation of the EOAc were tested in vitro on an isolated rabbit and rat jejunum mounted on an organ bath. Then, an isotonic transducer connected to an amplifier recorded the graph related to intestinal contractility. RESULTS: GC-MS analysis of the essential oil of Artemisia campestris L. showed the presence of m-Cymene (17.308%), Spathulenol (16.785%), ß Pinene (15.623%), α Pinene (11.352%), α.-Campholenal (8.848%) as main constituents. The EOAc gave a dose-dependent and reversible myorelaxant effect on the spontaneous contractions of jejunum isolated from rabbits, with an IC50 equal to 72.16 ± 15.93 µg/mL. This effect did not occur through adrenergic receptors. The EOAc has an antispasmodic effect on the contractions of rat jejunal induced by a medium with low (25 mM) or high concentration (75 mM) of KCl, and carbachol 10-6 M. The obtained inhibitory effects are comparable to those of a non-competitive antagonist of cholinergic receptors. The major compounds of EOAc allowed the establishment of a relationship between these phytoconstituents and the antispasmodic effect found by the EOAc. The obtained results are also supported by a docking study. CONCLUSION: The obtained results confirm favorably the use of Artemisia campestris L. in traditional Moroccan medicine for the treatment of digestive tract illness, which gives us a new route to valorize the effects obtained by a phytomedicine specific for the digestive tract.

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.