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This research explored the potential of a synthesised pyrazoline derivative 5‐ethoxy 5‐hydroxy 3‐methyls 4, 5‐dihydro 1Hpyrazol 1 yl (pyridine 4 yl) methanone [5‐E‐5‐H‐PD], against arthritis using a Complete Freund's Adjuvant (CFA)‐induced arthritis in a rat model. Sprague–Dawley rats were used to induce arthritis via subplantar injection of CFA (0.1 mL) into their right hind paw. Animals were divided into 6 groups ( n = 4): normal, arthritis, standard drug (methotrexate 1 mg/kg intraperitoneally), and 3 treatment groups receiving 5‐E‐5‐H‐PD, 10, 20 and 40 mg/kg orally for 21 days. Clinical signs (paw volume and arthritis score), pro‐inflammatory cytokines, and histopathological alterations were evaluated. The 5‐E‐5‐H‐PD groups showed a reduction in paw edema in a dose‐dependent manner. On day 21, paw volume in the 40 mg/kg dose animals decreased significantly to 2.31 ± 0.12 mm compared to 4.82 ± 0.14 mm in the disease animals ( p < 0.001). Arthritis scores reduced from 3.8 ± 0.2 (control) to 1.5 ± 0.3 in the high‐dose treatment group. Serum IL‐10, TNF‐α, and NF‐κB levels were significantly reduced to 66.75 ± 3.0 pg/mL, 34.50 ± 1.8 pg/mL and 9.50 ± 0.6 pg/mL respectively, compared to the arthritis induced rats 129.8 ± 2.0 pg/mL, 77.75 ± 1.5 pg/mL and 28.50 ± 1.3 pg/mL respectively, compared to the arthritis induced rats (112.3 ± 5.5, 96.8 ± 4.3, 123.1 ± 6.2 pg/mL, p < 0.001). Histopathology analysis confirmed reduced synovial hyperplasia and inflammatory infiltration in treated joints. The pyrazoline derivative, 5‐E‐5‐H‐PD, demonstrated significant anti‐arthritic effects in the CFA‐induced rat model by reducing inflammation, cytokine expression and joint destruction. These findings support further investigation into pyrazoline‐based compounds as promising therapeutic agents for RA.

Promising inhibitory activities of the parasite multiplication were obtained upon evaluation of in vivo antimalarial activities of new pyrazolylpyrazoline derivatives against Plasmodium berghei infected mice. Further evaluation of 5b and 6a against chloroquine-resistant strain (RKL9) of P. falciparum showed higher potency than chloroquine. In vitro antileishmanial activity testing against Leishmania aethiopica promastigote and amastigote forms indicated that 5b, 6a and 7b possessed promising activity compared to miltefosine and amphotericin B deoxycholate. Moreover, antileishmanial activity reversal of the active compounds via folic and folinic acids showed comparable results to the positive control trimethoprim, indicating an antifolate mechanism via targeting leishmanial DHFR and PTR1. The compounds were non-toxic at 125, 250 and 500 mg/kg. In addition, docking of the most active compound against putative malarial target Pf-DHFR-TS and leishmanial PTR1 rationalised the observed activities. Molecular dynamics simulations confirmed a stable and high potential binding of 7a against leishmanial PTR1.

Biothiols, characterized by their unique sulfhydryl (-SH) groups, possess excellent antioxidant properties, effectively neutralizing the damage to cellular structures caused by reactive oxygen species (ROS) in living organisms. Additionally, lysosomes play a crucial role in decomposing damaged biomolecules through the action of their internal enzymes, regulating the cellular redox state, and mitigating oxidative stress. To facilitate rapid monitoring of intracellular biothiols, particularly within lysosomes, we constructed a lysosome-targeted biothiol fluorescent probe, PHL-DNP, in this study. PHL-DNP exhibited excellent photophysical properties in an aqueous test system, including strong fluorescence enhancement response, excellent selectivity, and low detection limits (Cys 16.5 nM, Hcy 16.8 nM, GSH 21.3 nM, Cap 26.6 nM). These attributes enabled easy and efficient qualification of Cys on test strips and accurate determination of the effective content of captopril tablets. Notably, PHL-DNP demonstrated low cytotoxicity and precise lysosomal targeting. Through bioimaging, PHL-DNP not only monitored changes in biothiol levels under oxidative stress but also assessed biothiols in complex biological systems such as live HeLa cells, zebrafish, tumor tissue sections, and radish roots. This provides a promising tool for quantitative analysis of biothiols, disease marker detection, and drug testing.

Resistance to antibiotics is recognized as one of the biggest threats to human health worldwide. Frequent and unnecessary use of antibiotics has caused infectious agents to adapt to antibiotics and thus drugs have become less effective. The resistance to many antibiotics necessitates the discovery of new antibiotics. In this study, two new and 23 previously reported 2-pyrazoline derivatives and one hydrazone derivative were evaluated for their in vitro antibacterial and antifungal activities. For the determination of the minimum inhibitory concentration (MIC) values of compounds, microbroth dilution was used. The antimicrobial activities of the compounds were found in a wide range with MIC values of 32-512 μg/mL. The synthesized compounds showed moderate antimicrobial activity compared with the standards. They can be used as lead molecules for the synthesis of more effective compounds.

A series of new thiophene-containing triaryl pyrazoline derivatives, 3a–3t, were synthesized and evaluated regarding PI3K inhibition activity and anti-tumor potency based on a trial of introducing significant moieties, including pyrazoline and thiophene, and simplifying the parallel ring structures. Most of the tested compounds indicated potent PI3K inhibitory potency, with this series of compounds showing more potency for PI3Kγ than PI3Kα. The top hit 3s seemed more potent than the positive control LY294002 on inhibiting PI3Kγ (IC50 values: 0.066 μM versus 0.777 μM) and more selective from PI3Kα (Index values: 645 versus 1.74). It could be inferred that the combination of para- and meta-, as well as the modification of the electron-donating moieties, led to the improvement in potency. The anti-proliferation inhibitory activity and the enzymatic inhibition potency indicated consistent tendencies. The top hit 3s could inhibit the phosphorylation of Akt by inhibiting PI3K through the PI3K-Akt-mTOR pathway. The molecular docking simulation indicated that the binding pattern of 3s into PI3Kγ was preferable than that of PI3Kα, with more hydrogen bond, more π-involved interactions, and fewer π-sulfur interactions. The information in this work is referable for the further development of selective inhibitors for specific isoforms of PI3K.

Alzheimer's disease is a complex and progressive form of dementia. Its treatment relies on the behavioral and cognitive symptoms of an individual. Inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is a primary strategy used for treating Alzheimer's disease. Pyrazoline is a well-recognized nitrogen-containing five-membered heterocyclic skeleton. The unique structure of pyrazoline gives it a spatial configuration that leads to the multiple substitution pattern and advanced pharmacological properties. In an attempt to identify potent acetylcholine (AChE) and butyrylcholinesterase (BChE) inhibitors, new pyrazoline derivatives (IIIa–IIId) were synthesized using conventional method. The synthesised compounds were purified by column chromatography and were analysed using LCMS, 1 HNMR, 13 CNMR, and Mass Spectroscopic HR-MS techniques. The derivatives underwent initial screening for in-vitro antioxidant potential. The most potent compound, IIIa, showed IC50 values of 22.15 and 25.09 nM against AChE and BChE, respectively. Additionally, in-silico screening with AutoDock tools indicated that IIIa had promising binding affinities to the targets, with a binding energy (− 8.9 kcal/mol) comparable to donepezil (− 10.6 kcal/mol). The binding pattern of IIIa to AChE's active site justified its in-vitro inhibitory activity. These findings suggest that compound IIIa has potential as a new therapeutic agent for Alzheimer’s disease and is suitable for pre-clinical evaluation. Graphical abstract

Two novel 1,3,5-trisubstituted pyrazoline derivatives—1-acetyl-3-(4-methoxyphenyl)-5-(6-methoxy-2-naphthyl)-pyrazoline (2a) and 1-(4-nitrophenyl)-3-(4-methoxyphenyl)-5-(6-methoxy-2-naphtyl)-pyrazoline (2b)—were synthesized and their structures were determined by single crystal X-ray crystallography. Both of the two crystals exhibit twisted structures due to the large dihedral angles between the pyrazolinyl ring and the aromatic ring at the 5-position (88.09° for 2a and 71.26° for 2b). The optical–physical properties of the two compounds were investigated. The fluorescent emission of 2b arises from the 1,3-disubstituted pyrazoline chromophores and exhibits a red shift in polar solvents and solid-state, which could be attributed to photo-induced intramolecular charge transfer (ICT) from N1 to C3 in the pyrazoline moiety and the intermolecular interactions within the crystal. The fluorescent emissions of 2a (λmax 358–364 nm) in solvents and solid-state both come from 6-methoxy-2-naphthyl chromophores, which are fairly insensitive to the solvent polarity.

Two new pyrazoline derivatives, 3,5-bis(4-fluorophenyl)-4,5-dihydropyrazole-1-carboxamide (1) and 3,5-bis(4-fluorophenyl)-4,5-dihydropyrazole-1-carbothioamide (2), were synthesized by reacting 4,4'-difluoro chalcone with semicarbazide hydrochloride and thiosemicarbazide in ethanolic sodium hydroxide solution. Both the compounds were confirmed by single crystal X-ray diffraction data and supported by IR, NMR, and mass spectral data. In 1, crystal packing is stabilized by N–H…O hydrogen bonds and weak N–H...N, N–H…F and C–H…F intermolecular interactions. In 2, only weak N–H…F and N–H…S intermolecular interactions are observed. Crystal data: C16H13F2N3O, (1), Mr = 301.29, monoclinic, C2/c, a = 17.6219(6) Å, b = 10.8735(3) Å, c = 15.3216(5) Å, β = 102.864(3)°, V = 2862.11(16) Å3, Z = 8, T = 173 K, R(F) = 0.0511, wR(F2) = 0.1333; C16H13F2N3S, (2), Mr = 317.35, monoclinic, P21/c, a = 14.339(2) Å, b = 11.1478(17) Å, c = 9.541(2)(5) Å, β = 107.007(18)°, V = 1458.5(5) Å3, Z = 4, T = 173 K, R(F) = 0.0413, wR(F2) = 0.0959.

Inflammation of lungs is often related with the tuberculosis and convulsions are associated with the long term therapy of first line anti tubercular agents. Here in this present study an attempt has been made to synthesize the derivatives possesses all three activities. An efficient synthetic method has been established for the synthesis of new 2-Pyrazoline derivative. The synthesized compounds were evaluated for anti tubercular, anticonvulsant and anti-inflammatory activity. The observed increase in activities are attributed to the presence of 2-CH3, 4-NH2 in phenyl ring at 5-position of pyrazoline ring of newly synthesized compounds.