Pyrazoline Derivatives Research Articles

Synthesis, characterization, and antimicrobial evaluation of new pyrazolines incorporating imine moiety

A novel series of pyrazoline derivatives (3-9) was synthesized and identified by using several spectral analysis. Chalcone compound (1) was prepared as a starting material from the reaction of 4-aminoacetophenone and furan-2-carboxaldehyde in ethanol, using sodium hydroxide as a catalyst. Cyclization reaction of 1 by the action of hydrazine hydride afforded compound 2: 4-(5-(furan-2-yl)-4,5-dihydro-1H-pyrazol-3-yl) aniline. The target compounds (3-9) were obtained from the reaction of 2 with corresponding aldehydes in ethanol. The synthesized compounds were in vitro screened against several bacterial strains: Staphylococcus aureus, Staphylococcus espidermididis, Escherichia coli, Klebsiella sp, as well as, Candida albicans. These compounds exhibit a moderate to good activity.

Design and synthesis of novel pyrazoline derivatives for their spectroscopic, single crystal X-ray and biological studies

N-Acyl-2-pyrazolines have been synthesized via cyclization of chalcones with hydrazine hydrate in the presence of aliphatic acids. These pyrazolines (2a–c) were obtained in good yield (up to 84%), and the used method was found to be efficient for the preparation of pyrazolines. The structures were determined by FT-IR and NMR spectroscopic techniques and further confirmed by crystallographic diffraction study for a compound 2a. Single crystal diffraction studies help to find the intermolecular interactions which were endorsed by the Hirshfeld surface analysis. Furthermore, Hirshfeld analysis describe the different intermolecular contacts, among these H…H is the major contributor. The synthesized pyrazolines were determined for their efficacy against bacterial strains. The compound 2b displayed most promising antimicrobial activity against both Gram-positive and Gram-negative bacterial strains. The minimum inhibitory concentration (MIC) observed was 32 µg/mL against Staphylococcus aureus, Escherichia coli, and 64 µg/mL against Streptococcus pyogenes, S. typhimurium pathogens. The compounds (2a–c) were also explored for their inhibitory potential against a known therapeutic target and an essential bacterial enzyme, DNA gyrase, using computational methods.

Synthesis and (fluoro)solvatochromism of two 3-styryl-2-pyrazoline derivatives bearing benzoic acid moiety: A spectral, crystallographic and computational study

In this work we report the synthesis of two fluorescent 2-pyrazoline derivatives exhibiting remarkable (fluoro)solvatochromic behavior. The pyrazolines were synthesized in one step from the corresponding monocarbonyl curcuminoids and 4-hydrazinobenzoic acid in high yield and purity and were fully characterized by means of NMR and FT-IR spectroscopy and HRMS spectrometry. The structure of the novel derivative 2 was also characterized by means of X-ray crystallography. Both compounds were studied computationally in the gas phase. Additionally, the effects of solvent polarity on the absorption and fluorescence spectra of these derivatives were investigated in a solvent group consisting of various neat molecular solvents exhibiting hydrogen bond donating (HBD), hydrogen bond accepting (HBA), and/or dipolar behavior. The solvent effects observed were quantified and rationalized by employing suitable multiparametric Linear Solvation Energy Relationships (LSERs) involving dipolarity, HBD-acidity and HBA-basicity terms. The contribution of each of these parameters provided insights on the predominant solute-solvent interactions occurring in solution. Importantly, some differences in the (fluoro)solvatochromic aptitude/behavior were revealed among the derivatives and they were rationalized on the basis of their structural diversity.

Twisted intramolecular motion arrested in aggregated state emission and the nonlinear optical properties of pyrene pyrazoline derivatives

Heterocyclic pyrene pyrazoline moieties containing similar structures but with differences in thiophene (PPT), furan (PPF) and pyridine (PPP) substitutions at the terminal molecules were synthesized. Their aggregation behaviour in THF-water mixtures was investigated and results demonstrated that PPT and PPP exhibited aggregation-induced emission (AIE), whereas PPF exhibited aggregation-induced blue-shifted emission (AIBSE). PPT and PPP provided red-shifted emission, while PPF had observed blue-shifted emission at high water fractions of 70-90%, confirming that aggregation effects played a major role in the molecular structure. Two emission peaks from locally excited and twisted intramolecular charge transfer confirmed the twisted nature from the dihedral angle values of the free reorganized molecules that were completely restricted in high water fractions due to molecular aggregation. This was further confirmed from colour Commission Internationale de l'Eclairage values as well as dynamic light scattering analysis. Third-order nonlinear optical properties were studied using a Nd:Yag laser beam Z-scan technique at 532 nm. The open aperture Z-scan revealed that PPT and PPF towards the peak point endured strong saturable absorption, whereas PPP indicated a strong reverse saturable absorption process. The AIE and AIBSE mechanisms from undergoing restricted twisting intramolecular motion in the aggregated luminogens provide great insight into new developments in AIEgen materials for these optoelectronic materials.

Synthesis of Arylated 1,3,5-triphenyl Pyrazoline Derivatives by Suzuki-Miyaura Reactions With Antimicrobial Evaluation

The first palladium –catalyzed coupling reactions of 1,3,5-triphenyl pyrazoline are reported. The Suzuki-Miyaura reaction of 3-(4-bromophenyl)-1,5-diphenyl pyrazoline with one equivalent of arylboronic acids afforded 3-(biphenyl)-1,5-diphenyl pyrazoline in 65-78 % yield. While the Suzuki-Miyaura reactions of 3,5-bis(4-bromophenyl)-1-phenyl pyrazoline with two equivalent of arylboronic acids gave 3,5-bis(biphenyl)-1-phenyl pyrazoline in 55-75% yield. The characterization of the synthesized derivatives (5a-h) and (6a-h) was accomplished on the basis of NMR, FT-IR, and mass techniques. The newly pyrazoline derivatives have been investigated for their in vitro antibacterial activity against gram- negative and gram-positive bacteria. The di-coupling compounds (6a-h) exhibited promising antibacterial against all four bacterial strains compared to the mono-coupling compounds (5a-h) which displayed a slight activity. The compound 6d showed a potent activity significantly more active than Trimethoprim (100μg/ml).

A simple and efficient microwave assisted synthesis of pyrrolidinyl-quinoline based pyrazoline derivatives and their antimicrobial activity

A novel series of pyrrolidinyl-quinoline based pyrazoline derivatives are synthesised by the reaction of a series of Pyrrolidinyl-quinoline chalcones with hydrazine hydrate using Michael addition reaction conditions under microwave irradiation. All synthesized pyrzolines are screened for their in vitro antimicrobial activity against different bacterial and fungal pathogens. Majority of the synthesized compounds demonstrate moderate to good inhibition zones compared to the standard drugs.

New 2-Pyrazoline and Hydrazone Derivatives as Potent and Selective Monoamine Oxidase A Inhibitors

Thirty compounds having 1-[2-(5-substituted-2-benzoxazolinone-3-yl) acetyl]-3,5-disubstitutedphenyl-2-pyrazoline structure and nine compounds having N'-(1,3-disubstitutedphenylallylidene)-2-(5-substituted-2-benzoxazolinone-3-yl)acetohydrazide skeleton were synthesized and evaluated as monoamine oxidase (MAO) inhibitors. All of the compounds exhibited selective MAO-A inhibitor activity in the nanomolar or low micromolar range. The results of the molecular docking for hydrazone derivatives supported the in vitro results. Five compounds, 6 (0.008 μM, Selectivity Index (SI): 9.70 × 10-4), 7 (0.009 μM, SI: 4.55 × 10-5), 14 (0.001 μM, SI: 8.00 × 10-4), 21 (0.009 μM, SI: 1.37 × 10-5), and 42 (0.010 μM, SI: 5.40 × 10-6), exhibiting the highest inhibition and selectivity toward hMAO-A and nontoxic to hepatocytes were assessed for antidepressant activity as acute and subchronic in mice. All of these five compounds showed significant antidepressant activity with subchronic administration consistent with the increase in the brain serotonin levels and the compounds crossed the blood-brain barrier according to parallel artificial membrane permeation assay. Compounds 14, 21, and 42 exhibited an ex vivo MAO-A profile, which is highly consistent with the in vitro data.

Synthesis of Ligand para-di-2-(1-phenyl-3-pyridyl-4,5-dihydro-1H-pyrazol-5-yl) benzene by Aldol Condensation Method

Synthesis of pyrazoline derivative ligand para-di-2-(1-phenyl-3-pyridyl-4,5-dihydro-1H-pyrazol-5-yl)benzene has been successfully carried out by aldol condensation method using 2-acetyl pyridine and terephthalaldehyde in ethanol solution. The synthesis results are then reacted with excess phenyl hydrazine. The yield of ligand obtainedwas 63.10% of ayellow solid. The ligand was characterized using 1H-NMR spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, fourier transform infra-red (FTIR) spectroscopy and spectrofluorometer. The characterization with UV-Vis spectrophotometer results shows ligand has a large value of molar absorptivity (ε) at wavelength 236 nm and concentration 5x10-5 M.The results indicates that the ligand has a strong fluorescence intensity. It proved by peak emission at 467.5 nm (I = 4055 a.u).

WITHDRAWN: Phenyl-napthyl substituted pyrazole derivatives for synthesis, characterization and their antibacterial applications

The condensation of either acetophenone or substituted acetophenone with 1-naphthaldehyde in simple basic solutions such as NaOH, a significant number of phenyl and napthyl substituted chalcones have been synthesized. These substituted chalcones were reacted with hydrazine hydrate in the presence of pure sulphuric acid in obtaining linked to substituted pyrazoline derivatives. Compounds synthesized are distinguished by their chemical and spectroscopic properties. Synthesized compounds have been investigated against various bacterial species, such as Escherichia coli, Staphylococcus aureus, Klebsiella pneumonia, and Salmonella typhi, for antibacterial activity. It has been shown that substituted pyrazoline rings make a significant contribution to antibacterial action.

Pyrazoline analogs as potential anticancer agents and their apoptosis, molecular docking, MD simulation, DNA binding and antioxidant studies

N-formyl pyrazoline derivatives (3a–3l) were designed and synthesized via Michael addition reaction through cyclization of chalcones with hydrazine hydrate in presence of formic acid. The structural elucidation of N-formyl pyrazoline derivatives was carried out by various spectroscopic techniques such as 1H, 13C NMR, FT-IR, UV–visible spectroscopy, mass spectrometry and elemental analysis. Anticancer activity of the pyrazoline derivatives (3a–3l) was evaluated against human lung cancer (A549), fibrosarcoma cell lines (HT1080) and human primary normal lung cells (HFL-1) by MTT assay. The results of anticancer activity showed that potent analogs 3b and 3d exhibited promising activity against A549 (IC50 = 12.47 ± 1.08 and 14.46 ± 2.76 µM) and HT1080 (IC50 = 11.40 ± 0.66 and 23.74 ± 13.30 µM) but low toxic against the HFL-1 (IC50 = 116.47 ± 43.38 and 152.36 ± 22.18 µM). The anticancer activity of potent derivatives (3b and 3d) against A549 cancer cell line was further confirmed by flow cytometry based approach. DNA binding interactions of the pyrazoline derivatives 3b and 3d have been carried out with calf thymus DNA (Ct-DNA) using absorption, fluorescence and viscosity measurements, circular dichroism and cyclic voltammetry. Antioxidant potential of N-formyl pyrazoline derivatives (3a–3l) has been also estimated through DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical and H2O2. Results revealed that all the compounds exhibited significant antioxidant activity. In silico molecular modelling and ADMET properties of pyrazoline derivatives were also studied using PyRx software against topoisomerase II receptor with PDB ID: 1ZXM to explore their best hits. MD simulation of 3b and 3d was also carried out with topoisomerase II for structure–function correlation in a protein. HuTopoII inhibitory activity of the analogs (3a–3l) was examined by relaxation assay at varying concentrations 100–1000 µM.

In Situ Generation of Unstable Difluoromethylphosphonate-Containing Diazoalkanes and Their Use in [3 + 2] Cycloaddition Reactions with Vinyl Sulfones.

A [3 + 2] cycloaddition reaction of unstable difluoromethylphosphonate-containing diazoalkanes with vinyl sulfones under simple reaction conditions is developed, which provides an efficient route toward functionalized fluorinated pyrazolines derivatives in good chemical yields. The difluoro diazoalkanes are generated in situ using t-BuONO for the diazotization of (β-amino-α,α-difluoroethyl)phosphonates, and their stabilities and reactivities were carefully investigated.

Integrated computational approaches on pyrazoline derivatives as B-Raf kinase inhibitors for the development of novel anticancer agents

Raf kinases (rapidly accelerated fibrosarcoma) is related to retroviral oncogenes found in three different isoforms, A, B and C-Raf and played a significant part in mediating cell survival and proliferation. Various derivatives of B-Raf inhibitors are developed under laboratory level and some are under clinical trial studies. Here, we completed different computational techniques to identify features required for B-Raf kinase inhibitory activity by using 49 pyrazoline analogues. The development of pharmacophore, 3D QSAR analysis, virtual screening and docking studies were used for the development of novel compounds. For 3-dimentional-QSAR study, all compounds were divided into training and test set and determined the importance of substituents on 49 pyrazoline derivatives for B-Raf kinase inhibitory activity. The final models showed significant statistical values (R2 = 0.8325, Q2 = 0.5854) for atom based QSAR and (R2 = 0.7945, Q2 = 0.5808) for field based QSAR by using 3 partial least squares (PLS) factor. The validation results of 3D QSAR models showed R2 CV = 0.625, 0.5803, for both models (atom based and field based), consecutively. The docking studies of potent pyrazoline analogues (C1, C12, C14, C16n) showed good XP docking scores (-7.962, -8.864, -6.893, -7.171) with the interaction of amino acid residue such as PHE 583, CYS 532, SER 536 and ASP 594. The compounds ZINC13989686 and ZINC23908357 generated through virtual screening study showed their best docking scores -11.97 and -10.73 with receptor B-Raf kinase (PDB ID:2FB8). These data may be used for the development of potent compounds against B-Raf kinase.

Efficient Synthesis and Characterization of Anthracene based 1,3,5-Trisubstituted Pyrazoline Derivatives

A new series of anthracene scaffold containing 1,3,5-trisubstituted pyrazoline derivatives (3a-p) were synthesized and well characterized by 1H NMR, 13C NMR, FTIR, mass spectroscopic and elemental analysis methods. The reactions were carried out from anthracenyl pyrazolines (1a-p) and benzoyl chloride (2) in presence of anhydrous K2CO3 in acetone under reflux conditions for 2-7 h. The obtained yields were good to excellent (80-94%).

Возможности применения бромфенака в офтальмологической практике

Non-steroidal anti-inflammatory drugs (NSAIDs) are essential for the treatment of ocular disorders. While corticosteroids are the gold standard for inflammatory ocular diseases, comparative studies on the efficacy of NSAIDs and corticosteroids have demonstrated no significant differences in outcomes. Given the chemical structure of NSAIDs, it should be noted that salicylates, phenamates, and pyrazoline derivatives are either toxic or unstable. Solubilizers and preservatives also account for toxicity. Bromfenac-based medications are characterized by high safety and contain minimum benzalkonium chloride. This paper reviews advantages of a modern topical NSAID, bromfenac, for ocular use. This medication is more effective than diclofenac (by 3.7 times), amfenac (by 6.5 times), and ketorolac (by 18 times) in terms of inhibiting COG-2. Furthermore, the regimen of use (twice daily), no discomfort, and excellent safety profile with minimal adverse effects improve treatment adherence. In addition, Bromfenac, a topical antiinflammatory agent, improves patients’ satisfaction with surgical outcomes since patients achieve maximum possible visual acuity as early as possible. Keywords: non-steroidal anti-inflammatory drugs, NSAIDs, bromfenac, arachidonic acid, inflammation, corticosteroids, eye surgery, cataract, cystoid macular edema. For citation: Maksimov M.L., Zvegintseva A.A., Kanner I.D., Lapkin N.M. Bromfenac in ophthalmic practice. Russian Journal of Clinical Ophthalmology. 2021;21(4):241–248 (in Russ.). DOI: 10.32364/2311-7729-2021-21-4-241-248.

PEG-400 mediated synthesis, computational, antibacterial and antifungal studies of fluorinated pyrazolines

The present study explores a detailed comprehensive study on the computational, antibacterial and antifungal studies of pyrazoline derivatives. Four chalcones and corresponding 5-aryl-3-(4-fluorophenyl)-1-phenyl-4,5-dihydro-1H-pyrazoles were synthesized in PEG-400 and the structure of the pyrazolines were affirmed by IR, 1H NMR, and 13C NMR spectral techniques. The PEG-400 mediated synthesis of pyrazoline derivatives is effective, eco-friendly, and straightforward. The molecular structure, optimized geometrical parameters, UV and vibrational assignments were established by the density functional theory (DFT); the Becke-3-Lee-Yang-Parr (B3LYP) functional with 6-311++G(d,p) basis set. The absorption energies, excitation energy, oscillator strength, and transitions of four pyrazolines were computed using time-dependent density functional theory (TD-DFT) at B3LYP/6-311++G(d,p) level of theory for B3LYP/6-311++G(d,p) optimized geometries. The FMO study affirms that the molecule FPMP has the lowest bandgap with maximum charge transfer. A good correlation between theoretical and experimental UV and vibrational findings was obtained. Various global descriptors like were electronegativity, absolute hardness, global softness, global electrophilicity, chemical potential, and the maximum number of electrons transferred (Nmax) were calculated. The phenyl ring attached to nitrogen is likely to react with electrophiles, as shown in a molecular electrostatic potential surface analysis. The antibacterial screening was performed against two Gram-positive bacterial strains namely S. aureus and B. subtilis and two Gram-negative bacterial strains namely E. coli and P. vulgaris. On the other hand, the antifungal evaluation of the synthesized pyrazoline derivatives was carried out against two fungal strains namely A. niger and C. albicans.

Biological activities of a newly synthesized pyrazoline derivative 4-(3-(4-bromophenyl)-5-(2,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl) benzenesulfonamide (B4) compound on rainbow trout alevins, Oncorhynchus mykiss.

Biological activities of a newly synthesized pyrazoline derivative 4-(3-(4-bromophenyl)-5-(2,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl) benzenesulfonamide (B4) compound on rainbow trout alevins, Oncorhynchus mykiss.

Comparison of various synthesis methods and synthesis parameters of pyrazoline derivates.

Pyrazoline plays an important role in the development of heterocyclic chemistry theory and is widely used as a synthesis useful in organic synthesis. The structure of the pyrazoline derivative compound contains a 5-membered heterocyclic framework with two nitrogen atoms and one endocyclic double bond. The function of pyrazoline as a fragment was stable enough in the bioactive group to synthesize new compounds with various biological activities. Various methods that could be used for the synthesis of pyrazole derivatives were ultrasonic irradiation, microwave assistance, ionic liquids, grinding techniques, and conventional methods. However, the synthesis of pyrazoline derivatives using conventional methods had many problems, one of which is the product yield, which was <70%. Therefore, this article will discuss the importance of optimizing the synthesis reaction conditions by taking into account several synthesis parameters to get the best organic product results based on conventional methods. A literature search was conducted by employing PubChem, Chemspider Google Scholar, Research Gate, Science Direct, and Elsevier by selecting pyrazoline synthesis based on physicochemical profile, reaction mechanism, and synthesis method.

Design, Synthesis, Molecular Docking, and Anticancer Evaluation of Pyrazole Linked Pyrazoline Derivatives with Carbothioamide Tail as EGFR Kinase Inhibitors

Design, Synthesis, Molecular Docking, and Anticancer Evaluation of Pyrazole Linked Pyrazoline Derivatives with Carbothioamide Tail as EGFR Kinase Inhibitors

High dual-state blue emission of a functionalized pyrazoline derivative for picric acid detection

High dual-state blue emission of a functionalized pyrazoline derivative for picric acid detection.

Synthesis Characterization and In Vitro Antibacterial Activity of the N-Substituted Bis-Pyrazoline Derivative as Polycyclic Aromatic Compounds

N-substituted bis-pyrazolines were synthesized by the reaction of bis-chalcone with N-substituted thiosemicarbazide derivatives under basic conditions. Bis-chalcone was synthesized by the reaction of 1-(2,5-dimethylthiophen-3-yl)ethan-1-one with terephthalaldehyde under basic condition. The structure of the bis-pyrazoline derivatives has been confirmed by spectroscopic techniques such as FT-IR, 1H-NMR, 13C-NMR, and ESI-MS spectra, and the purity of the compound has been confirmed by the elemental analysis. The in vitro antibacterial activity of these pyrazoline derivatives was estimated against two Gram-positive and two Gram-negative bacterial strains by the disk diffusion method and minimum inhibitory concentration (MIC) method and the results were compared with standard drug Amoxicillin. The structure-activity relationship shows that the compound with choloro aromatic substituents at thiacarbomoyl group was more active than standard drug Amoxicillin.