Showing papers on "Pyrazole published in 2022"

In Vitro Antimicrobial Evaluation, Single-Point Resistance Study, and Radiosterilization of Novel Pyrazole Incorporating Thiazol-4-one/Thiophene Derivatives as Dual DNA Gyrase and DHFR Inhibitors against MDR Pathogens

Abstract: A series of thiazol-4-one/thiophene-bearing pyrazole derivatives as pharmacologically attractive cores were initially synthesized using a hybridization approach. All structures were confirmed using spectra analysis techniques (IR, 1H NMR, and 13C NMR). In vitro antimicrobial activities, including the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration (MBC/MFC), and time-kill assay, were evaluated for the most active derivatives 4a, 5a, 7b, 10, and 13. These derivatives were significantly active against the tested pathogens, with compound 7b as the most active derivative (MIC values range from 0.22 to 0.25 μg/mL). In the MBC and MFC, the active target pyrazole derivatives showed -cidal activities toward the pathogenic isolates. Further, the inhibition of biofilm formation of Staphylococcus aureus and Staphylococcus epidermidis was also carried out. Additionally, these derivatives displayed significant antibiofilm potential with a superior % reduction in the biofilm formation compared with Ciprofloxacin. The target derivatives behaved synergistically with Ciprofloxacin and Ketoconazole, reducing their MICs. Hemolytic results revealed that these derivatives were nontoxic with a significantly low hemolytic activity (%lysis range from 3.23 to 15.22%) compared with Triton X-100 and showed noncytotoxicity activity with IC50 values > 60 μM. In addition, these derivatives proved to be active DNA gyrase and DHFR inhibitors with IC50 ranging between 12.27–31.64 and 0.52–2.67 μM, respectively. Furthermore, compound 7b showed bactericidal activity at different concentrations in the time-kill assay. Moreover, a gamma radiation dose of 10.0 kGy was efficient for sterilizing compound 7b and enhancing its antimicrobial activity. Finally, molecular docking simulation of the most promising derivatives exhibited good binding energy with different interactions.

A Review of the Recent Development in the Synthesis and Biological Evaluations of Pyrazole Derivatives

Abstract: Pyrazoles are five-membered heterocyclic compounds that contain nitrogen. They are an important class of compounds for drug development; thus, they have attracted much attention. In the meantime, pyrazole derivatives have been synthesized as target structures and have demonstrated numerous biological activities such as antituberculosis, antimicrobial, antifungal, and anti-inflammatory. This review summarizes the results of published research on pyrazole derivatives synthesis and biological activities. The published research works on pyrazole derivatives synthesis and biological activities between January 2018 and December 2021 were retrieved from the Scopus database and reviewed accordingly.

Synthesis of a novel pyrazole heterocyclic derivative as corrosion inhibitor for low-carbon steel in 1M HCl: Characterization, gravimetrical, electrochemical, mathematical, and quantum chemical investigations

Abstract: A novel organic corrosion inhibitor, named 3, 5-dimethyl-1H-pyrazol-1-yl m (4-((4-hydroxybenzylidene) amino) phenyl) methanone (DPHM) has been effectively synthesized and characterized. The diagnosis of functional groups and constituents of DPHM has been conducted by FTIR, 1H NMR, and 13C NMR. The inhibitor efficacy for low-carbon steel in 1 M HCl was evaluated by using weight loss and electrochemical techniques. The inhibition efficiency was increased with increasing the temperature and DPHM concentrations. The inhibition efficiency approaches a maximum value of 89.5% at 400 ppm of DPHM and 60 °C. The efficiency of the inhibitor was attributed to the formation of a protective mono-layer on the steel surface. The Langmuir adsorption isotherm was used to inspect the adsorption process mechanism. Theoretical quantum chemical simulations were used to investigate the mechanism of inhibition. The results revealed that the DPHM was the donor of electron, while the steel surface was an electron acceptor. Mathematical and statistical modelling were used as powerful tool for data representation. Exponential model, with 0.992 correlation coefficient, was the most accurate one.

Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives

Abstract: Pyrazole and its derivatives are considered a privileged N-heterocycle with immense therapeutic potential. Over the last few decades, the pot, atom, and step economy (PASE) synthesis of pyrazole derivatives by multicomponent reactions (MCRs) has gained increasing popularity in pharmaceutical and medicinal chemistry. The present review summarizes the recent developments of multicomponent reactions for the synthesis of biologically active molecules containing the pyrazole moiety. Particularly, it covers the articles published from 2015 to date related to antibacterial, anticancer, antifungal, antioxidant, α-glucosidase and α-amylase inhibitory, anti-inflammatory, antimycobacterial, antimalarial, and miscellaneous activities of pyrazole derivatives obtained exclusively via an MCR. The reported analytical and activity data, plausible synthetic mechanisms, and molecular docking simulations are organized in concise tables, schemes, and figures to facilitate comparison and underscore the key points of this review. We hope that this review will be helpful in the quest for developing more biologically active molecules and marketed drugs containing the pyrazole moiety.

Novel nano silica assisted synthesis of azo pyrazole for the sustainable dyeing and antimicrobial finishing of cotton fabrics in supercritical carbon dioxide

Abstract: A new protocol was developed for the synthesis of azo pyrazole derivatives via one-pot reaction of β-ketonitriles and phenyl hydrazines in the presence of nano SiO2 as a mild catalyst. The synthesized dyes were elucidated using spectrophotometry, mainly NMR; FTIR; UV as well as elemental analysis. The dyeing was carried out utilizing supercritical carbon dioxide as a green medium. Outstanding deep color shades and excellent dye fixation were exhibited by all new dyes. Furthermore, the dyed samples revealed superlative color fastness. The biological evaluation of both the dyestuffs and the dyed samples showed overgrowing antimicrobial activity against the tested microorganisms. Therefore, our findings assured that disperse reactive dyes are the most commercially appropriate materials for dyeing cotton in supercritical carbon dioxide.

Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids

Abstract: Cancer is a complex disease, and its treatment is a big challenge, with variable efficacy of conventional anticancer drugs. A two-drug cocktail hybrid approach is a potential strategy in recent drug discovery that involves the combination of two drug pharmacophores into a single molecule. The hybrid molecule acts through distinct modes of action on several targets at a given time with more efficacy and less susceptibility to resistance. Thus, there is a huge scope for using hybrid compounds to tackle the present difficulties in cancer medicine. Recent work has applied this technique to uncover some interesting molecules with substantial anticancer properties. In this study, we report data on numerous promising hybrid anti-proliferative/anti-tumor agents developed over the previous 10 years (2011–2021). It includes quinazoline, indole, carbazole, pyrimidine, quinoline, quinone, imidazole, selenium, platinum, hydroxamic acid, ferrocene, curcumin, triazole, benzimidazole, isatin, pyrrolo benzodiazepine (PBD), chalcone, coumarin, nitrogen mustard, pyrazole, and pyridine-based anticancer hybrids produced via molecular hybridization techniques. Overall, this review offers a clear indication of the potential benefits of merging pharmacophoric subunits from multiple different known chemical prototypes to produce more potent and precise hybrid compounds. This provides valuable knowledge for researchers working on complex diseases such as cancer.

Synthesis, characterization, and in vitro antibacterial activity of some new pyridinone and pyrazole derivatives with some in silico ADME and molecular modeling study

Abstract: Abstract A new series of pyridine-2-one and pyrazole derivatives were designed and synthesized based on cyanoacrylamide derivatives containing 2,4-dichlro aniline and 6-methyl 2-amino pyridine as an aryl group. Condensation of cyanoacrylamide derivatives 3a–d with different active methylene (malononitrile, ethyl cyanoacetate cyanoacetamide, and ethyl acetoacetate) in the presence of piperidine as basic catalyst afforded the corresponding pyridinone derivatives 4a–c , 5 , 9 , and 13 . Furthermore, the reaction of cyanoacrylamide derivatives 3a–d with bi-nucleophile as hydrazine hydrate and thiosemicarbazide afforded the corresponding pyrazole derivatives 14a,b and 16 . The newly designed derivatives were confirmed and established based on the elemental analysis and spectra data (IR, 1 H NMR, 13 C NMR, and mass). The in vitro antibacterial activity was evaluated against four bacterial strains with weak to good antibacterial activity. Moreover, the results indicated that the most active derivatives 3a , 4a , 4b , 9 , and 16 might lead to antibacterial agents, especially against B. subtilis and P. vulgaris . The DFT calculations were performed to estimate its geometric structure and electronic properties. In addition, the most active pyridinone and pyrazole derivatives were further evaluated for in silico physicochemical, drug-likeness, and toxicity prediction. These derivatives obeyed all Lipinski’s and Veber’s rules without any violation and displayed non-immunotoxin, non-mutagenic, and non-cytotoxic. Molecular docking simulation was performed inside the active site of Topoisomerase IV (PDB:3FV5). It displayed binding energy ranging from -14.97 kcal/mol to -18.86 kcal/mol with hydrogen bonding and arene–cation interaction. Therefore, these derivatives were suggested to be good antibacterial agents via topoisomerase IV inhibitor. Graphical abstract

Recent advances in the applications of pyrazolone derivatives in enantioselective synthesis.

Abstract: Pyrazolones and pyrazoles, featuring nitrogen-nitrogen bonds, are two of the most important classes of heterocycles, owing to their widespread occurrence in medicinal chemistry and functional materials. The last decade has witnessed a rapid increase in the construction of chiral pyrazolone and pyrazole derivatives, with the application of pyrazolone derivatives as powerful synthons. Since our last review in 2018, a large number of new achievements has emerged in this area, requiring a timely update. Thus, this review summarizes these elegant achievements based on the multiple reactive sites of different pyrazolone synthons. In addition, important mechanisms and interesting biological investigations relating to the corresponding products are also discussed.

Design, synthesis, characterization, <i>in vitro</i> screening, molecular docking, 3D-QSAR, and ADME-Tox investigations of novel pyrazole derivatives as antimicrobial agents

Abstract: Novel pyrazoles were synthesized and evaluated for their antimicrobial activity. Molecular docking, 3D-QSAR, drug-likeness property and ADME-Tox studies were performed.

Novel nano silica assisted synthesis of azo pyrazole for the sustainable dyeing and antimicrobial finishing of cotton fabrics in supercritical carbon dioxide

Abstract: A new protocol was developed for the synthesis of azo pyrazole derivatives via one-pot reaction of β-ketonitriles and phenyl hydrazines in the presence of nano SiO2 as a mild catalyst. The synthesized dyes were elucidated using spectrophotometry, mainly NMR; FTIR; UV as well as elemental analysis. The dyeing was carried out utilizing supercritical carbon dioxide as a green medium. Outstanding deep color shades and excellent dye fixation were exhibited by all new dyes. Furthermore, the dyed samples revealed superlative color fastness. The biological evaluation of both the dyestuffs and the dyed samples showed overgrowing antimicrobial activity against the tested microorganisms. Therefore, our findings assured that disperse reactive dyes are the most commercially appropriate materials for dyeing cotton in supercritical carbon dioxide.

Visible Light-Mediated C(sp2)-H Selenylation of Amino Pyrazole and Amino Uracils in the Presence of Rose Bengal as an Organophotocatalyst.

Abstract: Herein, we report an efficient methodology for the synthesis of alkyl, benzyl, and phenyl selenoethers of aminopyrazoles and aminouracils by C(sp2)-H functionalization in the presence of visible light and Rose Bengal as an organophotocatalyst. The reaction of amino pyrazole/iosothiazole/isoxazole or amino uracils with 0.5 equivalent of diphenyl/dibenzyl/diethyl diselenides in the presence of visible light in acetonitrile medium and a catalytic amount of Rose Bengal provided the corresponding phenyl, benzyl, or ethyl selenoethers in good to very good yields. We have also utilized some of the selenylated aminopyrazoles for the preparation of pyrazole-fused dihydropyrimidines tethered with arylselenoethers by a catalyst-free one-pot three-component reaction. The notable features of this methodology are metal-free reaction conditions, good to very good yields, use of an organic photocatalyst, and wide substrate scope; it is also applicable to gram-scale synthesis and provides selenoethers of medicinally important heterocycles such amio-pyrazole, isoxazole, isothiazole, and uracils.

Discovery of novel pyrazole and pyrazolo[1,5‐a]pyrimidine derivatives as cyclooxygenase inhibitors (COX‐1 and COX‐2) using molecular modeling simulation

Abstract: Searching for effective and selective anti‐inflammatory agents, our study involved designing and synthesizing new pyrazole and pyrazolo[1,5‐a]pyrimidine derivatives 4–11. The structures of the synthesized derivatives were confirmed using different spectroscopic techniques. Virtual screening was achieved for the newly designed derivatives using in silico docking simulation inside the active sites of four proteins classified as two cyclooxygenases (COX)‐1 (PDB: 3KK6 and 4OIZ) and two COX‐2 (PBD: 1CX2 and 3LN1). Among them, six derivatives 4c, 5b, 6a, 7a, 7b, and 10b displayed the highest binding energy. These derivatives were evaluated for their in vitro COX‐1 and COX‐2 inhibitory activities and their selectivity indexes were calculated. Additionally, these derivatives displayed IC50 values ranging between 4.909 ± 0.25 and 57.53 ± 2.91 µM, and 3.289 ± 0.14 and 124 ± 5.32 µM, against COX‐1 and COX‐2, respectively. Furthermore, the tested derivatives were found to have selective inhibitory activity on the COX‐2 enzyme. Surprisingly, the two pyrazole derivatives 4c and 5b were found to be the most active, with IC50 values of 9.835 ± 0.50 and 4.909 ± 0.25 µM and 4.597 ± 0.20 and 3.289 ± 0.14 µM compared with meloxicam (1.879 ± 0.1 and 5.409 ± 0.23 µM) and celecoxib (5.439 ± 0.28 and 2.164 ± 0.09 µM) against COX‐1/‐2, respectively. Besides, two pyrazole derivatives, 4c and 5b, displayed a COX‐1/COX‐2 SI of 2.14 and 1.49. Computational techniques such as molecular docking, density function theory (DFT) calculation, and chemical absorption, distribution, metabolism, excretion, and toxicity evaluation were applied to explain the molecules’ binding mode, chemical nature, drug likeness, and toxicity prediction.

Radical-mediated C–N Bond Activation in 3,5-Diamino-4-nitro-1H-pyrazole towards High-energy and Insensitive Energetic Materials

Abstract: C–N bond activation has been recognized as a powerful methodology in organic synthesis, but C–N bond activation on monocyclic rings remains an intractable challenge, due to the high energy barrier...