In Vivo Potential Anti-Inflammatory Activity of Extracts from Calendula arvensis (CA) Flowers

Calendula arvensis (CA) had been reported in traditional Moroccan medicine to exhibit its extensive use to treat pain and inflammation. Therefore, the objective of this study was to evaluate the anti‐inflammatory activity of CA flowers. The methanol, aqueous, and hexane extracts (ME, AE, and HE) were investigated for inflammatory effects by using two methods, namely, carrageenan and experimental trauma‐induced hind paw edema in rats and using indomethacin (20 mg/kg body weight) as a standard drug. The results demonstrated that Calendula Arvensis CA extracts had significant anti‐inflammatory activity where the HE at the doses of 300 and 500 mg/kg p.o. (p < 0.001) had the best significant reduction and inhibition of edema with 51.08, 71.33 and 63.38, 67.33% induced by carrageenan and on experimental trauma induced rat paw edema at third hour, respectively, and similar as compared with standard drug indomethacin 20 mg/kg body weight p.o. (p < 0.001). These results indicate that it could be suggested as contributory effects to the use of CA flowers in the management of inflammation and pain conditions

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported

Synthesis, X-ray structure, vibrational spectroscopy, DFT, biological evaluation and molecular docking studies of (E)-N’-(4-(dimethylamino)benzylidene)-5-methyl-1H-pyrazole-3-carbohydrazide

New crystal, (E)-N’-(4-(dimethylamino)benzylidene)-5-methyl-1H-pyrazole-3-carbohydrazide (3) has been synthesized and characterized by FT-IR, NMR, ESI-MS and single crystal X-ray diffraction (XRD). The optimized molecular structures of free base and cationic species of (3) in gas phase and aqueous solution, vibrational frequencies and, corresponding vibrational assignments have been investigated experimentally and theoretically by using the B3LYP/6-31G∗ and B3LYP/6–311++G∗∗ methods. High solvation energy values are observed for both species of (3) in solution while the NBO and AIM studies support the higher stability of the cationic species in solution. The high energy values ΔEσ→σ∗ and ΔEσ→π∗ transitions, due to the planarity of both CH3 groups linked to N atom, could support the high reactivities of its free base and cationic species, as compared with naloxone, cocaine and scopolamine. Complete vibrational assignments of 105 and 108 vibration modes expected for free base and cationic species of (3) together with the corresponding harmonic force constants are here reported. In vitro antidiabetic and antioxidant activities were revealed for (3). The molecular docking studies of the title compound revealed that it may exhibit anti-diabetic activity via inhibition of α-glucosidase PDB:3A4A enzyme

New Pyrazole-Hydrazone Derivatives: X-ray Analysis, Molecular Structure Investigation via Density Functional Theory (DFT) and Their High In-Situ Catecholase Activity

The development of low-cost catalytic systems that mimic the activity of tyrosinase enzymes (Catechol oxidase) is of great promise for future biochemistry technologic demands. Herein, we report the synthesis of new biomolecules systems based on hydrazone derivatives containing a pyrazole moiety (L1–L6) with superior catecholase activity. Crystal structures of L1 and L2 biomolecules were determined by X-ray single crystal diffraction (XRD). Optimized geometrical parameters were calculated by density functional theory (DFT) at B3LYP/6–31G (d, p) level and were found to be in good agreement with single crystal XRD data. Copper (II) complexes of the compounds (L1–L6), generated in-situ, were investigated for their catalytic activities towards the oxidation reaction of catechol to ortho-quinone with the atmospheric dioxygen, in an attempt to model the activity of the copper containing enzyme tyrosinase. The studies showed that the activities depend on four parameters: the nature of the ligand, the nature of counter anion, the nature of solvent and the concentration of ligand. The Cu(II)-ligands, given here, present the highest catalytic activity (72.920 μmol·L−1·min−1) among the catalysts recently reported in the existing literature

In Silico Identification of Promising New Pyrazole Derivative-Based Small Molecules for Modulating CRMP2, C-RAF, CYP17, VEGFR, C-KIT, and HDAC&mdash;Application towards Cancer Therapeutics

Despite continual efforts being made with multiple clinical studies and deploying cutting-edge diagnostic tools and technologies, the discovery of new cancer therapies remains of severe worldwide concern. Multiple drug resistance has also emerged in several cancer cell types, leaving them unresponsive to the many cancer treatments. Such a condition always prompts the development of next-generation cancer therapies that have a better chance of inhibiting selective target macromolecules with less toxicity. Therefore, in the present study, extensive computational approaches were implemented combining molecular docking and dynamic simulation studies for identifying potent pyrazole-based inhibitors or modulators for CRMP2, C-RAF, CYP17, c-KIT, VEGFR, and HDAC proteins. All of these proteins are in some way linked to the development of numerous forms of cancer, including breast, liver, prostate, kidney, and stomach cancers. In order to identify potential compounds, 63 in-house synthesized pyrazole-derivative compounds were docked with each selected protein. In addition, single or multiple standard drug compounds of each protein were also considered for docking analyses and their results used for comparison purposes. Afterward, based on the binding affinity and interaction profile of pyrazole compounds of each protein, potentially strong compounds were filtered out and further subjected to 1000 ns MD simulation analyses. Analyzing parameters such as RMSD, RMSF, RoG and protein&ndash;ligand contact maps were derived from trajectories of simulated protein&ndash;ligand complexes. All these parameters turned out to be satisfactory and within the acceptable range to support the structural integrity and interaction stability of the protein&ndash;ligand complexes in dynamic state. Comprehensive computational analyses suggested that a few identified pyrazole compounds, such as M33, M36, M72, and M76, could be potential inhibitors or modulators for HDAC, C-RAF, CYP72 and VEGFR proteins, respectively. Another pyrazole compound, M74, turned out to be a very promising dual inhibitor/modulator for CRMP2 and c-KIT proteins. However, more extensive study may be required for further optimization of the selected chemical framework of pyrazole derivatives to yield improved inhibitory activity against each studied protein receptor

Synthesis, structural characterizations, in vitro biological evaluation and computational investigations of pyrazole derivatives as potential antidiabetic and antioxidant agents

Abstract In this study, a two pyrazole derivatives; 2-(5-methyl-1H-pyrazole-3-carbonyl)-N-phenylhydrazine-1-carboxamide (Pyz-1) and 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (Pyz-2) were synthesized and characterized by 13C-NMR, 1H-NMR, FT-IR, and mass spectrometry. A complete molecular structures optimization, electronic and thermodynamic properties of Pyz-1 and Pyz-2 in gas phase and aqueous solution were predicted by using hybrid B3LYP method with the 6-311++G** basis sets. Pyz-1 and Pyz-2 were evaluated in vitro for their anti-diabetic, antioxidant and xanthine oxidase inhibition activities. For anti-diabetic activity, Pyz-1 and Pyz-2 showed a potent α-glucosidase and α-amylase inhibition with IC50 values of 75.62 ± 0.56, 95.85 ± 0.92 and 119.3 ± 0.75, 120.2 ± 0.68 µM, respectively, compared to Acarbose (IC50(α-glucosidase) = 72.58 ± 0.68 µM, IC50(α-amylase) = 115.6 ± 0.574 µM). In xanthine oxidase assay, Pyz-1 and Pyz-2 exhibited remarkable inhibitory ability with IC50 values 24.32 ± 0.78 and 10.75 ± 0.54 µM, respectively. The result of antioxidant activities showed that the title compounds have considerable antioxidant and radical scavenger abilities. In addition, molecular docking simulation was used to determine the binding modes and energies between the title compounds and α-glucosidase and α-amylase enzymes