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Journal of Computational Chemistry Dec 2021Pyrazole derivatives correspond to a family of heterocycle molecules with important pharmacological and physiological applications. At present, we perform a density...
Pyrazole derivatives correspond to a family of heterocycle molecules with important pharmacological and physiological applications. At present, we perform a density functional theory (DFT) calculations and a quantitative structure-activity relationship (QSAR) evaluation on a series of 1-(4,5-dihydro-1H-pyrazol-1-yl) ethan-1-one and 4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives as an epidermal growth factor receptor (EGFR) inhibitory activity. We thus propose a virtual screening protocol based on a machine-learning study. This theoretical model relates the studied compounds' biological activity to their calculated physicochemical descriptors. Moreover, the linear regression function is used to validate the model via the evaluation of Q and Q parameters for external and internal validations, respectively. Our QSAR model shows a good correlation between observed activities IC and predicted ones. Our model allows us to mitigate time-consuming problems and waste chemical and biological products in the preclinical phases.
Topics: Density Functional Theory; ErbB Receptors; Humans; Models, Molecular; Pyrazoles; Quantitative Structure-Activity Relationship
PubMed: 34609748
DOI: 10.1002/jcc.26761 -
Bioorganic Chemistry Aug 2019Reported herein are the design, synthesis, and pharmacologic evaluation of novel pyrazole and pyrazoline derivatives. The study presents the effect of lengthening of...
Reported herein are the design, synthesis, and pharmacologic evaluation of novel pyrazole and pyrazoline derivatives. The study presents the effect of lengthening of carbon chain in different pyrazole derivatives bearing various amine moieties. Combination of pyrazoline ring with either pyrazole or quinoline rings (Floctafenine derivatives) through synthesis of chalcones and their cyclization into pyrazolines was involved. The structures of target compounds were confirmed by elemental analysis and spectral data. All the newly synthesized compounds were investigated for their anti-inflammatory and analgesic activities compared to Indomethacin as a reference drug. Docking and molecular modeling study was initiated to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior of the most potent compounds 14b, 15b and 22 through their various interactions with the active site of COX-2 isozyme. Protein Data Bank (PDB) file of COX II enzyme with the code 4Z0L and its co-crystallized ligand Indomethacin were used for this purpose. The binding affinity was evaluated via comparing the scoring energy (S) and amino acid interactions of novel compounds with Indomethacin.
Topics: Acetic Acid; Administration, Oral; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Dose-Response Relationship, Drug; Drug Design; Edema; Female; Male; Mice; Models, Molecular; Molecular Structure; Motor Activity; Pyrazoles; Rats; Structure-Activity Relationship
PubMed: 31185391
DOI: 10.1016/j.bioorg.2019.103023 -
Pest Management Science Jun 2023Whilst there are several methods to control weeds, which continuously plague farmers around the globe, the application of small molecular compounds is still the most...
BACKGROUND
Whilst there are several methods to control weeds, which continuously plague farmers around the globe, the application of small molecular compounds is still the most effective technology to date. Plants can evolve to become resistant to PPO-inhibitors, a class of herbicides in commercial use since the 1960s. It is therefore essential to continuously develop new herbicides based on this mode-of-action with enhanced intrinsic activity, an improved resistance profile and favourable physicochemical properties. Based on an Amaranthus PPO crystal structure and subsequent modelling studies, halogen-substituted pyrazoles have been investigated as isosteres of uracil-based PPO-inhibitors.
RESULTS
By combining structural features from the commercial PPO-inhibitors tiafenacil and pyraflufen-ethyl and by investigating receptor-binding properties, we identified new promising pyrazole-based lead structures showing strong activity in vitro and in vivo against economically important weeds of the Amaranthus genus: A. retroflexus, and resistant A. palmeri and A. tuberculatus.
CONCLUSION
The present work covers a series of novel PPO-inhibiting compounds that contain a pyrazole ring and a substituted thioacetic acid sidechain attached to the core phenyl group. These compounds show good receptor fit in line with excellent herbicidal activity against weeds that plague corn and rice crops with low application rates. This, in combination with promising selectivity in corn, have the potential to mitigate and affect weeds that have become resistant to some of the current market standards. Remarkably, some of the novel PPO-inhibitors outlined herein show efficacies against economically important weeds that were superior to recently commercialized and structurally related tiafenacil. © 2023 Society of Chemical Industry.
Topics: Herbicides; Protoporphyrinogen Oxidase; Plague; Pyrazoles; Plant Weeds
PubMed: 36815643
DOI: 10.1002/ps.7425 -
Chemosphere Dec 2019Inability to remove biologically toxic and persistent contaminants is a critical issue in traditional water treatment processes. In this study, a novel 3D macroporous...
Inability to remove biologically toxic and persistent contaminants is a critical issue in traditional water treatment processes. In this study, a novel 3D macroporous RuO (3D-RuO) electrode with uniform and interconnected cavities has been fabricated via templated electrodeposition approach for treatment of persistent pyrazole. The physicochemical properties of the electrodes are characterized by means of SEM, BET, XRD, LSV and CV measurements. The results show that structural features of the 3D-RuO play important roles in the electrocatalysis performance. Thanks to the abundant crystal defect sites, 3D-RuO electrode possesses more mesopores within the skeleton, resulting in 17.9 and 2.2 times larger specific surface area compared to traditional flat thermal-deposited (TF-RuO) and electrodeposited RuO (EF-RuO) respectively. At a current density of 5 mA cm, the pyrazole removal rate on 3D-RuO is 1.7 times and 1.3 times that of TF-RuO and EF-RuO. The energy consumption for 50% of pyrazole removal on 3D-RuO is 0.05 kWh gpyrazole, much lower than that of TF-RuO (0.11 kWh gpyrazole) and EF-RuO (0.075 kWh gpyrazole). The improved removal performance of 3D-RuO electrode is attributed to its strong electro-adsorption capacity (270.3 μg cm), leading to enhanced mass transfer of pollutants to the electrode surface. The mass transfer coefficient (κ) is estimated as 2.4 × 10 m s for 3D-RuO, which is 3.9 and 2.3 times as much as that of TF-RuO and EF-RuO. Finally, contribution of different electron transfer approaches to pyrazole degradation under anodic polarization was investigated by ROS scavenging experiments.
Topics: Adsorption; Electrodes; Pyrazoles; Ruthenium Compounds; Wastewater; Water; Water Pollutants, Chemical; Water Purification
PubMed: 31401428
DOI: 10.1016/j.chemosphere.2019.124471 -
Bioorganic & Medicinal Chemistry Letters Sep 2009Potent 5-HT(2A) inverse-agonists containing phenyl-pyrazole ureas with an amino side chain were identified. Optimization of this series resulted in selective compounds...
Potent 5-HT(2A) inverse-agonists containing phenyl-pyrazole ureas with an amino side chain were identified. Optimization of this series resulted in selective compounds that proved effective in modulating 5HT-induced amplification of ADP-stimulated human platelet aggregation.
Topics: Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Pyrazoles; Receptor, Serotonin, 5-HT2A; Serotonin 5-HT2 Receptor Agonists; Structure-Activity Relationship; Urea
PubMed: 19665894
DOI: 10.1016/j.bmcl.2009.07.073 -
Molecules (Basel, Switzerland) Jun 2024In this research, with an aim to develop novel pyrazole oxime ether derivatives possessing potential biological activity, thirty-two pyrazole oxime ethers, including a...
In this research, with an aim to develop novel pyrazole oxime ether derivatives possessing potential biological activity, thirty-two pyrazole oxime ethers, including a substituted pyridine ring, have been synthesized and structurally identified through H NMR, C NMR, and HRMS. Bioassay data indicated that most of these compounds owned strong insecticidal properties against , , , and at a dosage of 500 μg/mL, and some title compounds were active towards at 500 μg/mL. Furthermore, some of the designed compounds had potent insecticidal effects against , , or at 100 μg/mL, with the mortalities of compounds , , , , , , , , , , and against , in particular, all reaching 100%. Even when the dosage was lowered to 20 μg/mL, compound also expressed 50% insecticidal activity against , and compounds , , , , , and displayed more than 60% inhibition rates against . The current results provided a significant basis for the rational design of biologically active pyrazole oxime ethers in future.
Topics: Pyrazoles; Oximes; Insecticides; Animals; Drug Design; Structure-Activity Relationship; Ethers; Molecular Structure; Pyridines; Moths
PubMed: 38930832
DOI: 10.3390/molecules29122767 -
Bioorganic & Medicinal Chemistry Letters Aug 2012As a part of our research to develop novel antitubercular and antimicrobial agents, a series of 3-(4-chlorophenyl)-4-substituted pyrazoles have been synthesised. These...
As a part of our research to develop novel antitubercular and antimicrobial agents, a series of 3-(4-chlorophenyl)-4-substituted pyrazoles have been synthesised. These compounds were tested for antitubercular activity in vitro against Mycobacterium tuberculosis H37Rv strain using the BACTEC 460 radiometric system, antifungal activity against a pathogenic strain of fungi and antibacterial activity against gram-positive and gram-negative organisms. Among them tested, many compounds showed good to excellent antimicrobial and antitubercular activity. The results suggest that hydrazones, 2-azetidinones and 4-thiazolidinones bearing a core pyrazole scaffold would be potent antimicrobial and antitubercular agents.
Topics: Anti-Infective Agents; Antitubercular Agents; Fungi; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Pyrazoles; Structure-Activity Relationship
PubMed: 22695129
DOI: 10.1016/j.bmcl.2012.05.063 -
European Journal of Medicinal Chemistry Feb 2010Reactions of 5-hydrazino-1,3-dimethyl-4-nitro-1H-pyrazole (1) with substituted benzaldehydes (2-5) in methanol gave the new substituted benzaldehyde...
Reactions of 5-hydrazino-1,3-dimethyl-4-nitro-1H-pyrazole (1) with substituted benzaldehydes (2-5) in methanol gave the new substituted benzaldehyde (1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)hydrazone Schiff base ligands (6-9) benzaldehyde (1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)hydrazone (H-BDH, 6), 2,3-dimethoxybenzaldehyde (1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)hydrazone (MeO-BDH, 7), 4-chlorobenzaldehyde (1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)hydrazone (Cl-BDH, 8), and 4-hydroxybenzaldehyde (1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)hydrazone (OH-BDH, 9) in moderate to excellent yields. Reactions of these pyrazole-based Schiff bases with [PdCl(2)(NCPh)(2)] in acetone at room temperature gave the trans-palladium(II) complexes trans-[PdCl(2)(L)(2)] (10-13) (L=6-9). The isolated compounds were characterized by their physical properties, elemental analysis, IR-, MS (EI)- and NMR-spectroscopy. The cytotoxic effect of these complexes against the fast growing head and neck squamous carcinoma cells SQ20B and SCC-25 has been studied. The influence was dose dependent and varies by cell type. The complexes 11, 12, and 13 had higher clonogenic cytotoxic effect than cisplatin when tested on SQ20B cell line.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Humans; Ligands; Organometallic Compounds; Palladium; Pyrazoles; Stereoisomerism
PubMed: 19913953
DOI: 10.1016/j.ejmech.2009.10.029 -
Carbohydrate Research Sep 2011A facile synthesis of sugar-pyrazole derivatives has been accomplished by condensation of sugar-chalcone with hydrazine hydrate under neutral conditions resulting in...
A facile synthesis of sugar-pyrazole derivatives has been accomplished by condensation of sugar-chalcone with hydrazine hydrate under neutral conditions resulting in yields of 70-85%. The products are characterized by FTIR and NMR spectroscopy and by elemental analysis. The β-anomeric forms for these derivatives were assigned by NMR spectroscopy.
Topics: Carbohydrates; Glycosides; Ketones; Magnetic Resonance Spectroscopy; Molecular Structure; Pyrazoles; Spectroscopy, Fourier Transform Infrared
PubMed: 21784420
DOI: 10.1016/j.carres.2011.06.019 -
Bioorganic & Medicinal Chemistry Jul 2010Two series of pyrazole derivatives designing for potential EGFR kinase inhibitors have been discovered. Some of them exhibited significant EGFR inhibitory activity....
Two series of pyrazole derivatives designing for potential EGFR kinase inhibitors have been discovered. Some of them exhibited significant EGFR inhibitory activity. Compound 3-(3,4-dimethylphenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (C5) displayed the most potent EGFR inhibitory activity with IC₅₀ of 0.07 μM, which was comparable to the positive control erlotinib. Docking simulation was performed to position compound C5 into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicating that some of the pyrazole derivatives own high antiproliferative activity against MCF-7. Compound C5 showed significant antiproliferative activity against MCF-7 with IC₅₀ of 0.08 μM. Therefore, compound C5 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent.
Topics: Antineoplastic Agents; Binding Sites; Cell Line, Tumor; Computer Simulation; ErbB Receptors; Humans; Neoplasms; Pyrazoles; Thioamides; Thiourea
PubMed: 20627597
DOI: 10.1016/j.bmc.2010.05.034