Pyrazole Moiety Research Articles

Synthesis, Structural Characterization and Hirshfeld Surface Analysis of a Novel Cd(II) Coordination Polymer with Mixed N- and O-donor Linker

In the present study, we report the room temperature synthesis of a novel two-dimensional (2D) coordination polymer (CP) having the formula {[Cd(H-PCA)2(H2O)].0.5(H2O).0.5(CH3OH)}n (CP1), where H-PCA represents 4-pyrazolecarboxylate. The synthesis of CP1 was achieved through a one-pot reaction, involving the self-assembly of Cd(OAc)2·2H2O and the multitopic mixed N- and O-donor ligand, 4-pyrazolecarboxylic acid (H2-PCA), in methanol. This method demonstrated high yield and purity, enabling the facile production of multigram quantities of CP1 within a short timeframe. Notably, the synthetic procedure selectively deprotonates the carboxylic acid group while retaining the pyrazole moiety in its protonated form.CP1 has been thoroughly characterized using various analytical techniques, including single-crystal X-ray diffraction, FTIR spectroscopy, elemental analysis, scanning electron microscopy, thermogravimetric analysis, and powder X-ray diffraction. The structural analysis revealed that CP1 features a 3, 5-connected binodal net with the point symbol {4.5.6}{4.55.63.7}, leading to a unique –ths net topology. Through hydrogen bonding connections between adjacent 2D sheets, CP1 further extends into a three-dimensional (3D) supramolecular network due to the presence of coordinated water molecules and the protonated pyrazole group. Additionally, a 3D Hirshfeld Surface analysis accompanied by quantitative 2D fingerprint plots was also investigated to explore the intermolecular interactions.

Exo- or endo-1H-pyrazole metal coordination modulated by the polyamine chain length in [1 + 1] condensation azamacrocycles. Binuclear complexes with remarkable SOD activity.

The Cu2+ complexes of three [1 + 1] azacyclophane macrocycles having the 1H-pyrazole ring as the spacer and the pentaamine 1,5,8,11,15-pentaazadecane (L1) or hexaamines 1,5,8,12,15,19-hexaazanonadecane (L2) and 1,5,9,13,17,21-hexaazaheneicosane (L3) as bridges show endo- coordination of the pyrazolate bridge giving rise to discrete monomeric species. Previously reported pyrazolacyclophanes evidenced, however, exo-coordination with the formation of dimeric species of 2 : 2, 3 : 2 or even 4 : 2 Cu2+ : L stoichiometry. The complexes have been characterized in solution using potentiometric studies, UV-Vis spectroscopy, paramagnetic NMR, cyclic voltammetry and mass spectrometry. The measurements show that all three ligands have as many protonation steps in water as secondary amines are in the bridge, while they are able to form both mono- and binuclear Cu2+ species. The crystal structures of the complexes [Cu(HL1)Br]Br(1+x)(ClO4)(1-x)·yH2O (1) and [Cu2(H-1L2)Cl(ClO4)](ClO4)·H2O·C2H5OH (2) have been solved by X-ray diffraction studies. In 1 the metal ion lies at one side of the macrocyclic cavity being coordinated by one nitrogen of the pyrazolate moiety and the three consecutive nitrogen atoms of the polyamine bridge. The other nitrogen of the pyrazole ring is hydrogen-bonded to an amine group. In 2 the two metal ions are interconnected by a pyrazolate bis(monodentate) moiety and complete their coordination spheres with three amines and either a bromide or a perchlorate anion, which occupy the axial positions of distorted square pyramid geometries. Paramagnetic NMR studies of the binuclear complexes confirm the coordination pattern observed in the crystal structures. Cyclic voltamperommetry data show potentials within the adequate range to exhibit superoxide dismutase (SOD) activity. The IC50 values calculated by McCord-Fridovich enzymatic assays show that the binuclear Cu2+ complexes of L2 and L3 have SOD activities that rank amongst the highest ones reported so far.

A small molecule iCDM-34 identified by in silico screening suppresses HBV DNA through activation of aryl hydrocarbon receptor

IFN-alpha have been reported to suppress hepatitis B virus (HBV) cccDNA via APOBEC3 cytidine deaminase activity through interferon signaling. To develop a novel anti-HBV drug for a functional cure, we performed in silico screening of the binding compounds fitting the steric structure of the IFN-alpha-binding pocket in IFNAR2. We identified 37 compounds and named them in silico cccDNA modulator (iCDM)-1–37. We found that iCDM-34, a new small molecule with a pyrazole moiety, showed anti-HCV and anti-HBV activities. We measured the anti-HBV activity of iCDM-34 dependent on or independent of entecavir (ETV). iCDM-34 suppressed HBV DNA, pgRNA, HBsAg, and HBeAg, and also clearly exhibited additive inhibitory effects on the suppression of HBV DNA with ETV. We confirmed metabolic stability of iCDM-34 was stable in human liver microsomal fraction. Furthermore, anti-HBV activity in human hepatocyte-chimeric mice revealed that iCDM-34 was not effective as a single reagent, but when combined with ETV, it suppressed HBV DNA compared to ETV alone. Phosphoproteome and Western blotting analysis showed that iCDM-34 did not activate IFN-signaling. The transcriptome analysis of interferon-stimulated genes revealed no increase in expression, whereas downstream factors of aryl hydrocarbon receptor (AhR) showed increased levels of the expression. CDK1/2 and phospho-SAMHD1 levels decreased under iCDM-34 treatment. In addition, AhR knockdown inhibited anti-HCV activity of iCDM-34 in HCV replicon cells. These results suggest that iCDM-34 decreases the phosphorylation of SAMHD1 through CDK1/2, and suppresses HCV replicon RNA, HBV DNA, and pgRNA formation.

Formation of (Aza)fulvenallene, Cyanocyclopentadiene, and (Aza)fluorenes in the Thermal Rearrangements of Indazoles, Azaindazoles, and Homoquinolinic Anhydride.

Flash vacuum pyrolysis (FVP) of pyrazoles and indazoles constitutes a valuable route to carbenes and nitrenes. In this study, we employed M062X and CCSD(T) calculations to provide a mechanistic rationale for the formation of fulvenallene and fluorenes from indazoles and the corresponding formation of azafulvenallene 15, cyanocyclopentadiene 19, and azafluorenes, e.g. 45, from azaindazoles, e.g. 12, and from homoquinolinic anhydride. The results reveal the importance of initial tautomerization in the pyrazole moiety of 7-azaindazole 12, which drives the mechanism toward 2-diazo-3-methylene-2,3-dihydropyridine 29 and hence 3-methylene-2,3-dihydropyridin-2-ylidene 26, followed by Wolff-type ring contraction to 1-azafulvenallene 15. This path has a calculated activation energy ∼10 kcal/mol lower than that for an alternate route involving ring opening to 3-diazomethylpyridine, dediazotization, and rearrangement of 3-pyridylcarbene to azacycloheptatetraene and phenylnitrene 24. FVP of 2,5-diphenyltetrazoles and phenyl(pyridyl)tetrazoles leads to nitrile imines, which cyclize to 3-phenylindazoles and -azaindazoles. Nitrogen elimination from these (aza) indazoles results in the formation of (aza) fluorenes, for which two alternate mechanisms are described: route A by rearrangement of (aza) indazoles to diazo(aza)cyclohexadienes and (aza)cyclohexadienylidenes and route B by rearrangement to diaryldiazomethanes and diarylcarbenes. Both paths are energetically feasible, but path A is preferred and corresponds to the azafluorenes obtained experimentally.

Extension of Pt–Ag cluster units by incorporating silver salts

Abstract A sterically controlled Z-shaped Pt2Ag2 complex showed a metalation reaction with a Ag ion via the formation of the thermodynamically unfavorable Pt2Ag2 complex with U-shaped configuration. Multiple dative bond formation between Pt and an additional Ag ion endowed enough thermodynamic stability on the Pt2Ag3 cluster to overcome the unfavorable steric effect from bulky substituents on the ligands in the U-shaped structure. A single crystal X-ray structural analysis revealed dimerized structure of the cationic Pt2Ag3 complex units bridged by [Ag2(OTf)4]2− (OTf− = triflate anion) via strong Ag–π coordination with pyrazole moiety in the solid state. The heteropolynuclear complexes showed photoluminescence properties depending on the structure of the Pt–Ag clusters.

Highly Enantioselective 6π Photoelectrocyclizations Engineered by Hydrogen Bonding.

Photochemical electrocyclization reactions are valued for both their ability to produce structurally complex molecules and their central role in elucidating fundamental mechanistic principles of photochemistry. We present herein a highly enantioselective 6π photoelectrocyclization catalyzed by a chiral Ir(III) photosensitizer. This transformation was successfully realized by engineering a strong hydrogen-bonding interaction between a pyrazole moiety on the catalyst and a basic imidazolyl ketone on the substrate. To shed light on the origin of stereoinduction, we conducted a comprehensive investigation combining experimental and computational mechanistic studies. Results from density functional theory calculations underscore the crucial role played by the prochirality and the torquoselectivity in the electrocyclization process as well as the steric demand in the subsequent [1,4]-H shift step. Our findings not only offer valuable guidance for developing chiral photocatalysts but also serve as a significant reference for achieving high levels of enantioselectivity in the 6π photoelectrocyclization reaction.

Exploring the Therapeutic Potential of Benzohydrazide Derivatives: Synthesis, Characterization, and Profound Antimicrobial Activity

A compelling series of innovative benzohydrazide derivatives has been successfully synthesized via a facile condensation reaction, involving the strategic union of benzohydrazide with diverse substituted formyl pyrazole derivatives under reflux conditions. The structural elucidation of the newly formed compounds was meticulously accomplished through a battery of spectroscopic techniques, including FT-IR, NMR (1H & 13C), and mass spectrometry, ensuring the confirmation of their molecular integrity. This synthetic approach not only provides a robust method for obtaining a versatile array of compounds but also holds promise for their biological activities. The incorporation of both pyrazole and benzohydrazide moieties renders these derivatives compelling candidates for extensive pharmacological investigations. The flexibility to introduce diverse substituents onto the phenyl rings of these compounds presents an exciting avenue for tailoring their properties to specific applications. Notably, compounds 6b, 6c, and 6d demonstrated remarkable antibacterial and antifungal activities against tested microorganisms, establishing their potential as potent antimicrobial agents. Beyond their antimicrobial efficacy, the structural diversity of these compounds positions them as valuable entities for medicinal chemistry research, offering avenues for the development of novel pharmaceutical agents. The present study underscores the significance of these benzohydrazide derivatives in the realm of medicinal chemistry, hinting at their potential to catalyze advancements in therapeutic agent development.

Design, Synthesis and Anticancer Evaluation of New 1-allyl-4-oxo-6-(3,4,5- trimethoxyphenyl)-1,4-dihydropyrimidine-5-carbonitrile Bearing Pyrazole Moieties.

pyrimidine and pyrazole have various biological and pharmaceutical applications such as antibacterial, antifungal, antileishmanial, anti-inflammatory, antitumor, and anti-cancer. In this search, the goal is to prepare pyrimidine-pyrazoles and study their anticancer activity. 1-allyl-4-oxo-6-(3,4,5-trimethoxyphenyl)-1,4-dihydropyrimidine-5-carbonitrile bearing pyrazoles (4,6-8) have been synthesized. Firstly, the reaction of 1-allyl-2-(methylthio)-4-oxo-6- (3,4,5-trimethoxyphenyl)-1,4-dihydropyrimidine-5-carbonitrile (1) with chalcones 2a-b produced the intermediates 3a-b. The latter was reacted with hydrazine hydrate to give the targets 4a-b. On the other hand, hydrazinolysis of compound 1 yielded the hydrazino derivative 5 which upon reaction with chalcones 2c-i or 1,3-bicarbonyl compounds afforded the compounds 6-8. Finally, the new compounds were characterized by spectral data (IR, 1H NMR, 13C NMR) and elemental analysis. Moreover, they were evaluated for Panc-1, MCF-7, HT-29, A-549, and HPDE cell lines as anticancer activity. All the tested compounds 3,4,6-8 showed IC50 values > 50 μg/mL against the HPDE cell line. Compounds 6a and 6e exhibited potent anticancer activity where the IC50 values in the range of 1.7- 1.9, 1.4-182, 1.75-1.8, and 1.5-1.9 μg/mL against Panc-1, MCF-7, HT-29, and A-549 cell lines. New pyrimidine-pyrazole derivatives were simply synthesized, in addition, some of them showed potential anticancer activity.

Synthesis, Characterization, and Antioxidant Screening of Some New Azo Compounds Containing Pyrazole Moiety from Metoclopramide Drug

In this work, some new pyrazole derivatives were prepared through the reaction of the diazonium salt of metoclopramide with acetylacetone to give 5-chloro-N-(2-(diethylamino)ethyl)-4-((2,4-dioxopentan-3-yl) diazenyl)-2-methoxybenzamide (1) in 80% yield. Compound 1 was then reacted with some hydrazine derivatives to afford the corresponding pyrazole derivatives in 75-93% yields. Some new azo compounds (6-10) were also prepared in 77-95% yields by treatment of the diazonium salt of metoclopramide with some phenol and aniline derivatives. The prepared compounds were characterized using FT-IR and 1H NMR spectroscopy. Some of these compounds were then tested to see how well they worked as antioxidants.

Pyrazole-directed functionalization of activated collagen fiber for highly specific capture of iodine vapor

The highly specific capture of radioactive iodine vapor generated during spent fuel reprocessing exerts a pivotal influence on ensuring the sustainable development of nuclear energy. In this study, we successfully prepared pyrazole-directed functionalized leather waste collagen fiber composite (Pyrazole@ACF) by immobilizing pyrazole ring through Schiff base reaction on the alkaline-activated collagen fiber (ACF) interface. The peak capacity for capturing iodine vapor by Pyrazole@ACF is shown to be 3.494 g/g, which is markedly higher compared to that of ACF (0.928 g/g). Pyrazole@ACF was characterized using FE-SEM, FT-IR, and XPS, revealing the release of numerous active functional groups from ACF that facilitated iodine-induced capture and pyrazole ring immobilization. Furthermore, the interaction mechanism between functional groups and iodine was further elucidated through Density Functional Theory (DFT) calculations. The iodine capture effect of Pyrazole@ACF is primarily ascribed to the existence of active functional groups (C = O, –OH, and –NH2) on ACF, as well as the charge transfer occurring between the grafted pyrazole moieties and iodine, ultimately leading to the generation of I3− polyiodide complexes and subsequent iodine capture. Consequently, Pyrazole@ACF exhibits a strong specific capture capability for iodine vapor, along with excellent thermal stability and iodine immobilization properties, meeting the application requirements under practical conditions.

Synthesis and Insecticidal Assessment of Some Innovative Heterocycles Incorporating a Pyrazole Moiety

The compound 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (1) was utilized as a fundamental component in the synthesis of novel N-phenyl pyrazole derivatives. Substituted N-phenyl pyrazole compounds including 2-cyano-3-(1,3-diphenyl-1H-pyrazol-4-yl)-N-Substituted-acrylamide derivatives (4a–h), 4-(hydrazineylidenemethyl)-1,3-diphenyl-1H-pyrazole (6) and 2-cyano-N'-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-acetohydrazide (11) were obtained in moderate yields through the reaction of 1 with 2-cyano-N-substituted acetamide derivatives 3a–h, hydrazine hydrate, and cyanoacetohydrazide under basic-catalyzed conditions, respectively. Moreover, hydrazinyl-pyarzole 6 reacted with 4,5,6,7-tetrabromoisobenzofuran-1,3-dione (7) to afford 4,5,6,7-tetrabromo-2-(((1,3-diphenyl-1H-pyrazol-4-yl)methylene)amino)- isoindoline-1,3-dione (8). Furthermore, pyrazoloacetohydrazide 11 is condensed with salicylaldehyde derivatives 12a–e to give pyrazolochromene carbohydrazide derivatives 13a–e. Also, acetohydrazide 11 refluxed with N, N-dimethylformamide dimethyl acetal to produce 2-cyano-3-(dimethylamino)-N'-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)acrylohydrazide (15), which upon exposure to acidic conditions underwent cyclization to form 4-((dimethylamino)methylene)-6-(1,3-diphenyl-1H-pyrazol-4-yl)pyridazine-3,5(4H,6H)-dione (16). The newly synthesized compounds were identified and confirmed using elemental and spectral data analyses as IR, MS, 1H NMR, 13C NMR, and 2D NMR analysis (H-H COSY, HSQC, HMBC, and NOSEY), Also, DFT studies were done to prove the geometrical optimization and spatial distributions orbitals of compounds 4a and 11. The toxicity of N-phenylpyrazole compounds was tested against the corn leaf aphid (Rhopalosiphum maidis) and the mealy plum aphid (Hyalopterus pruni). Compounds 4c, 13c, and 13d were found to be the most potent to control the two insects compared with acetamiprid 20% SP recommended by the Ministry of Agriculture. The biochemical investigation of insects was studied to the most effective compounds on insects as well, and the toxicity of compounds 4c, 13c, and 13d was studied on the predators (Hippodamia variegata, Cydonia vicina isis, Cydonia vicina nilotica, and 4th instar larvae H. variegata) under laboratory conditions.

Synthesis, Characterization and In-Vitroanti-Tumor Activity of Some Novel Pyrazole Derivatives

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 a potent anti-inflammatory, antipsychotic , anti-obesity drug, an analgesic, and anti-depressant agents 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 heterocyclic can be traced in a number of well-established drugs belonging to different categories with diverse therapeutic activities. Aim of the present study is to synthesize and characterize various 4-[1-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)3,4-(phenyl]-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one derivatives using an efficient Scheme. The synthesized compounds (1-10) were evaluated for their in vitro anti-cancer activity.In order to develop potent anti-cancer agents, a novel series of pyrazole derivatives were synthesized and the structures of all compounds were confirmed by spectral studies. MTT assay has been employed to study anti-proliferative activity of these compounds with four human cancer cell lineDLD1 (Human Colorectal Adenocarcinoma) at various concentration (6.25-100µg/mL). The results revealed that compounds VEPD and 4MEPD shows goodanti-tumoractivity and the other compounds shows moderate activity against theDLD1cell line.

Design, synthesis and anti-hyperglycemic assessments of novel 5-benzylidenethiazolidine-2,4-dione derivatives as PPAR-γ agonist

The treatment of diabetes mellitus still relies predominantly on peroxisome proliferator-activated receptor-γ (PPAR-γ) therapy, known for its effectiveness. In this present study, a novel series of benzylidene-linked thiazolidine-2,4-dione compounds was conceptualized, synthesized, and subjected to assessment for their potential antidiabetic properties. Notably, among the compounds examined, 5-((Z)-4-(((E)-Propylidene)amino)benzylidene)thiazolidine-2,4-dione, designated as 4c, emerged as the most promising candidate, exhibiting the highest PPAR-γ agonistic activity with an EC50 value of 0.35 ± 0.52 μM. Additionally, molecular docking investigations were conducted on twelve 2,4-thiazolidinedione compounds, with a pyrazole moiety incorporated, within the ligand binding domain of PPAR-γ. Compound 4c, in particular, demonstrated a Glide XP score of −9.104, surpassing the score of the crystal ligand (Glide XP score = −7.482). Notably, both exhibited similar interactions with key amino acids, including HIE323, SER289, and GLN286. Furthermore, three derivatives (4a-c) with promising PPAR-γ agonistic activity and favorable molecular docking scores underwent in vivo evaluation for their capacity to lower blood glucose levels using a streptozotocin-induced diabetic mice model. In comparison to the reference drug pioglitazone, Compound 4c displayed commendable in-vivo performance across multiple parameters, encompassing serum HDL, serum LDL, serum total cholesterol, and serum triglyceride levels. Molecular dynamics simulations provided insights into the impact of ligand 4c, indicating its role in enhancing protein stability and rigidity. These findings emphasize its potential as a potent protein inhibitor, thus opening novel avenues for the intelligent design of molecules with high efficacy in the management of hyperglycemia.

A novel pyrazole–pyridine derivative (PPD) targets specific biological pathways in the larval stages of the northern house mosquito Culex pipiens Linnaeus (Diptera: Culicidae)

BackgroundMosquitoes cause a variety of health problems in humans and pets. So, the control of mosquito larvae is one of the best ways to avoid health problems arising from diseases transmitted by these insects. There are various control mechanisms including mechanical, biological and chemical control. The latter, despite the presence of some obstacles associated with its use, is preferred because of its ability to supply rapid management results.ResultA novel laboratory-synthesized chemical compound containing pyrazole and pyridine moieties (pyrazole–pyridine derivatives, PPD) was used to control and address the biological effects on Culex pipiens mosquito second larval instar. A sublethal concentration (LC30) of PPD inhibited larval growth by about 50%. Furthermore, the developmental time of larvae into pupae and the emergence of adults from the pupal stages were increased by about 20% and 17%, respectively. The ultrastructural studies on the midgut cells revealed that treated larvae suffered dramatic degeneration in the gastric caeca and the posterior midgut cells, while the anterior midgut epithelium appeared with an abundance of lysosomal activities. Additionally, treated larvae showed fluctuated activities in the levels of the detoxifying enzymes and increased levels in total antioxidants.ConclusionsThese results clearly show that pyrazole and pyridine moieties containing compounds can be used against larval stages of C. pipiens.

Green synthesis of highly functionalized heterocyclic bearing pyrazole moiety for cancer-targeted chemo/radioisotope therapy

New derivatives of heterocyclic bearing pyrazole moiety were synthesized (eight new compounds from 2 to 9) via green synthesis methods (microwave-assisted and grinding techniques). 4,6-Diamino-1,3-diphenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (2) shows high anti-cancer activity against both HepG2 and HCT-116 with IC50 of 9.2 ± 2.8 and 7.7 ± 1.8 µM, respectively, which referenced to 5-Fu which is showing activity of 7.86 ± 0.5 and 5.35 ± 0.3 against both HepG2 and HCT-116, respectively. The cytotoxic activity against HCT-116 and HepG2 was slightly decreased and slightly increased, respectively, by a different pyrazole moiety (compound 5). Pharmacokinetics of compound 2 was carried out using the radioiodination technique in tumour-bearing Albino mice which shows good uptake at the tumour site. The biodistribution showed high accumulation in tumour tissues with a ratio of 13.7% ID/g organ after one hour in comparison with 2.97% ID/g organ at normal muscle at the same time point. As I-131 has maximum beta and gamma energies of 606.3 and 364.5 keV, respectively, therefore the newly synthesized compound 2 may be used for chemotherapy and TRT.

Functionalized collagen fiber with specific recognition sites for highly efficient iodine capture: theoretical calculations and experimental verification

The efficient and specific capture of radioiodine vapor during the post-fuel processing is essential for the sustainable development of nuclear energy. In this study, Density Functional Theory (DFT) calculations were employed to investigate the adsorption capabilities and mechanisms of iodine vapor by composite materials (Pyrimidine@ACF, Pyrazole@ACF, and Thiazole@ACF) obtained through functionalization of activated carbon fiber (ACF) with pyrimidine, pyrazole and thiazole moieties. The DFT results indicate that the nitrogen heterocycle 3-aminopyrazole exhibits the highest iodine adsorption energy (-11.06 kJ/mol). Among the active groups on the ACF, the carbonyl moiety (C = O) demonstrates the utmost iodine adsorption energy (-45.04 kJ/mol). The designed composite functional materials show a substantial enhancement in iodine adsorption capability, with Pyrazole@ACF displaying the maximum iodine adsorption energy of -63.53 kJ/mol. The experiments demonstrate that the iodine vapor capture capacity of composite functional materials is significantly enhanced compared to ACF (1.010 g/g). Notably, Pyrazole@ACF demonstrates an iodine vapor capture capacity of 2.586 g/g. The iodine capture mechanism of the composite materials is primarily attributed to the active functional groups on ACF, as well as the charge transfer between the nitrogen heterocycles introduced through functionalization and iodine molecules. This ultimately leads to the capture of iodine molecules by the formation of I3- polyiodides. Consequently, the nitrogen heterocycles functionalized activated collagen fiber composite material can be considered as an ideal candidate for efficient and specific capture of iodine vapor in radioactive gaseous effluents.

Pharmacophore-based synthesis of pyrazole analogues as artificial antibiotics targeting Salmonella Typhi

The pharmacological potential of the pyrazole moiety is demonstrated by their presence in a wide range of therapeutic agents spanning various categories. Notable examples include: Celecoxib: A potent anti-inflammatory drug, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB): An antipsychotic medication, Rimonabant: An anti-obesity drug, Difenamizole: An analgesic, Betazole: An H2-receptor agonist, Fezolamide: An antidepressant agent. These examples underscore the versatility and efficacy of the pyrazole nucleus in the development of pharmacologically active compounds across different therapeutic domains [1–12]. In our study, we computationally designed 23 different derivatives of pyrazole compounds and analysed their Pharmacokinetics (ADMET) properties in the QikProp module on Schrodinger's Maestro platform. Among them, high throughput optimised and promising analogues of 11 pyrazole compounds were synthesised and analysed by NMR and LCMS for structural configuration. The synthesised compounds were initially analysed for cytotoxicity by MTT assay and found to have lower toxicity profiling in 7 pyrazole derivatives. Further, the compounds were investigated for their antibacterial activity against Salmonella Typhi by broth dilution and disk diffusion methods, where four compounds (P4, P14, P19, and P20) exhibit a potential growth inhibitory activity as compared with standard antibiotics which commercially used for S. Typhi infection. Further, to explore the mode of action on the growth suppression of S. Typhi was investigated by performing molecular docking with outer membrane protein (cell wall inhibition) and DNA-dependant RNA polymerase (transcriptional arrest) of S. Typhi, wherein all four tested probes exhibited the binding interaction localised at the active domains of the foresaid target protein. The P14 compound exhibits the maximum score of least binding energy at -8.174 kcal/mol against OMP C, whereas the P4 remains at -5.575 kcal/mol against the DNA-dependent RNA polymerase. This observation is clearly evident in the antagonistic effects of the synthesised derivatives on the growth of S. Typhi.

A novel Zn(II) coordination polymer with mixed N- and O-donor linker: Room temperature synthesis, comprehensive characterization and Hirshfeld surface analysis

The present study describes the room temperature synthesis of a new two-dimensional (2D) coordination polymer (CP) having the formula [Zn(H-PCA)2]n (CP1), where H-PCA stands for 4-pyrazolecarboxylate. The mixture of Zn(OAc)2·2H2O and multitopic mixed N- and O-donor 4-pyrazolecarboxylic acid (H2-PCA) were self-assembled in a one-pot in methanol. The synthesis produced good yield and purity, and this method makes it simple to obtain multigram quantities of CP1 within a short period. Notably, this synthetic method selectively deprotonates the carboxylic acid group while maintaining pyrazole moiety in its protonated form. CP1 has been characterized by single-crystal X-ray diffraction, FTIR spectroscopy, elemental analysis, scanning electron microscopy, thermogravimetric analysis and powder X-ray diffraction. CP1 exhibits a 4-connected, 2-fold interpenetrated 2D network with the point symbol {44.62} – sql net topology. Due to the presence of the protonated pyrazole, these 2D layers further extended into a three-dimensional (3D) non-porous supramolecular network through strong 'intermolecular' NH···O hydrogen bonds between adjacent layers. Additionally, a 3D Hirshfeld Surface analysis accompanied by quantitative 2D-fingerprint plots was also investigated to explore the 'intermolecular' interactions.

Discovery of small molecule modulators targeting β-catenin interactions using molecular docking and molecular dynamics strategy

The rapid activation of signaling pathways is the primary factor responsible for the progression of serious malignancies. Particularly, overexpression of β-catenin is one of the preventative oncogenic biomarkers that is widely present in many tumor types. Therefore, we have designed an integrated pharmacophore strategy to discover the potential inhibitor against β-catenin. Primarily, the ligand-, energy-optimized and the receptor cavity-based pharmacophore hypothesis AAHHR, ADR and ANNNRRR were constructed to screen the active molecules from the database. In order to improve the screening efficacy, the resultant molecules were scrutinized by integrating the results obtained through docking and MM/GBSA calculations. Further, the common hit molecules were subjected to a pharmacokinetic and toxicity study which resulted in two potent β-catenin inhibitors: BAS03014832 and BAS01077671. The existence of thiazole and pyrazole moiety is responsible for the anti-neoplastic activity of these molecules. Finally, a deep neural network technique was used to assess the inhibitory action of these compounds across 66 colorectal cancer cell lines. Overall, the results of our study portray a pathway for the experimental biologist in developing selective β-catenin inhibitors.

Facile one pot three component synthesis, characterization, and molecular docking simulations of novel α-aminophosphonate derivatives based pyrazole moiety as potential antimicrobial agent.

An efficient method has been developed for the synthesis of novel α-aminophosphonates (AAP) (3a-m) through a one-pot three-component reaction of 1,3-disubstituted-1H-pyrazol-5-amine, aromatic aldehydes, and phosphite using lithium perchlorate as catalyst. All newly synthesized compounds were characterized via different spectroscopic techniques. The synthesized compounds' mode of action was investigated using molecular docking against the outer membrane protein A (OMPA) and exo-1,3-beta-glucanase, with interpreting their pharmacokinetics aspects. The results of the antimicrobial effectiveness of these compounds revealed a broad spectrum of their biocidal activity and this in-vitro study was in line with the in- silico results. Additionally, it has been demonstrated that these compounds exhibited a minimum inhibitory concentration (MIC) with significant activity at low concentrations (7.5-30.0 mg/mL). Further, the radical scavenging (DPPH*) activity of the synthesized compounds fluctuated, with compounds 3h, 3a, and 3f showing the highest antioxidant activity. Overall, the formulated compounds can be employed as antimicrobial and antioxidant agents in medical applications.