Abstract Cancer progression is driven by dysregulation of cyclin-dependent kinase 2 (CDK2), a critical cell cycle regulator. This study employed an integrated computational approach combining Density Functional Theory (DFT), molecular docking, molecular dynamics (MD) simulations, and MM-PBSA calculations to evaluate 2-thiohydantoin derivatives as CDK2 inhibitors. DFT calculations revealed compounds 2b-e narrowest lowest unoccupied molecular orbital (LUMO)- highest occupied molecular orbital (HOMO) gaps (3.02–3.26 eV in DMSO) and highest electrophilicity indices (> 3.20 eV), indicating enhanced reactivity toward biological targets. QTAIM and Fukui function analyses identified key electrophilic centers (C2, O12, C14) and hydrogen bonding sites essential for protein interactions. Molecular docking against CDK2 (PDB: 1HCK) showed compounds 2c, 2d, and 2b exhibited superior binding affinities (-9.312, -9.303, and − 9.269 kcal/mol) compared to ATP (-8.460 kcal/mol), forming critical hydrogen bonds with Lys33 and Thr14. The 10 ns MD simulations confirmed stable binding, with compound 2f maintaining highest conformational stability (RMSD ~ 0.05 nm) and robust hydrogen bonding (mean: 2.70 bonds). MM-PBSA analysis revealed compound 2d achieved optimal binding affinity (ΔG_bind = -34.50 ± 0.42 kcal/mol) through balanced van der Waals interactions (-50.74 kcal/mol) and minimal desolvation penalty (52.40 kcal/mol). Compounds 2b, 2c, 2d, and 2f emerged as lead candidates for experimental validation as next-generation CDK2-targeted anticancer agents.

DNA topoisomerase II (Topo II) is essential for maintaining DNA topology during replication, transcription, and chromosome segregation. Its increased expression is associated with tumor progression, which makes it an appealing target for anticancer therapy. However, clinically used Topo II inhibitors such as etoposide and doxorubicin are limited by toxicity and resistance, illustrating the importance of safer, more effective chemotherapeutic scaffolds. This study reports the rational design, synthesis, and biological evaluation of a novel series of hydrazone derivatives incorporating a 1,8-naphthyridine core as potential Topo II inhibitors. Hybrid molecules were generated by integrating hydrazone moieties with the naphthyridine scaffold and characterized using standard spectroscopic techniques. Their biological activities were assessed via in vitro cytotoxicity assays and Topo II inhibition tests. Complementary computational investigations, including density functional theory (DFT), molecular docking, molecular dynamics (MD) simulations, MM/PBSA binding free-energy analysis, and per-residue MM/GBSA free-energy decomposition analysis, were performed to explore electronic properties, ligand–target interactions, and binding determinants. Among the synthesized series, compound 3b displayed notable antiproliferative activity, particularly against the HL-60 (TB) leukemia cell line (GI₅₀ = 1.99–3.02 μM), and exhibited potent Topo II inhibition (IC₅₀ = 1.79 ± 0.73 μM), outperforming doxorubicin (IC₅₀ = 3.08 ± 0.59 μM) under the same conditions. Computational modelling supported these findings by indicating stable binding conformations and suggesting a potential DNA-intercalative binding mode within the Topo II catalytic environment. However, this interaction remains a computational prediction that requires experimental validation.

A novel class of 5-(3,5-dimethoxybenzylidene)-2-thioxoimidazolidin-4-one-based derivatives, linked to various alkyl and aryl substituents 1a-d and 2a-h, was designed and synthesized as promising candidates for anti-colon cancer therapy with multi-targeting kinase suppression activity. The antiproliferative effect of the new compounds was assessed against HT-29 using the MTT assay. The congeners 1c and 2h demonstrated the most potent suppressive effects, with IC50 values 1.828 and 2.197 μg/mL, respectively. The latter derivatives were evaluated as multi-kinase inhibitors against VEGFR-2, c-Met, and PIM-1, exhibiting promising activity with IC50 values ranging from 0.081 ± 0.003 to 0.433 ± 0.017 μg/mL. Moreover, 2h induced an apoptotic effect and cell cycle arrest at G0/G1 of the mitotic cycle in HT-29 cells. Furthermore, 2h upregulated the oncogenic parameters, including caspase-3, caspase-9, and the Bax/Bcl-2 ratio. The docking results showed that compounds 1c, 2h, and 2e had strong binding energies and effectively interacted with the active sites of the VEGFR-2, c-Met, and PIM-1 receptors. According to the in-silico ADMET analysis the new compounds are anticipated to exhibit promising oral bioavailability, desirable drug-like qualities, and minimal toxicity risks. Molecular dynamics (MD) simulations indicated that 2h interacts consistently with the c-MET, PIM-1, and VEGFR-2 receptors. These results reinforce the potential of these compounds as candidates for further drug development.

Objective: The objective of the current study was to create a pyrazole scaffold derivation that could be used as a medication to treat specific protein and gene alterations without causing harm to healthy cells. Methods: Focusing on this class of compounds, we report an efficient synthesis of substituted bipyrazole derivative and structural characterizations have been carried out including spectroscopic (FTIR, 1 H NMR, 13 C NMR, and MS) and physiochemical methods. The newly synthesized derivative was evaluated for their anti-proliferative activity against sixty cancer cell lines at the (NCI/USA) for the one and five-dose assay. Additionally, kinase profiling evaluation was used to screen for further exploration of its putative anticancer pathways. For the target compound, additional ADMET studies were carried out. Results: The acquired data demonstrated a potent effect against nearly the full panel giving GI 50 (MG-MID: 3.59 μM). Also, liver of the DENA-rats treated with this product exhibited a remarkable improvement in the hepatic configuration with no marked acute toxicity and normalization of all liver parameters including AST, ALT, and ALP activities and the total bilirubin level. Also, the data indicated that the target compound could exert its cytotxic activity through dual-targeted kinase inhibitory potency against VEGFR-2 and CDK-2/cyclin A2 with (IC 50 = 3.37 ± 1.00 and 0.73 ± 0.22 μM, respectively) relating with the references sorafenib and roscovitine (IC 50 = 1.60 ± 0.10 and 0.68 ± 1.10 μM, respectively). ADMET studies, demonstrating its good drug-like characteristics and reduced toxicity. Conclusions: This work offers a very effective new molecule that may serve as an excellent starting point for the development of prospective anti-tumor drugs for additional preclinical research.

The reaction between different arylhydrazones and ninhydrin (= indene-1,2-3-trione) in acetonitrile at room temperature is described to produce novel bioactive 1-(3-chlorophenyl)indeno[1,2-c]pyrazol-4(1H)-one analouges. In evaluations of the ability to inhibit the growth of different human cell lines and some pathogenic bacterial strains in vitro, compounds 3c and 3f showed significant potency compared with the reference drugs. Both derivatives interacted well with the active site of the BRAF protein, according to molecular docking studies.

Synthesis, biological evaluation, and molecular docking of pyrazoline-linked benzenesulfonamides and diaryl 1,5-benzothiazepines prepared from new chalcones are described and elucidated. Novel compounds were studied for their in vitro anticancer profiles on HepG2, HEK-293, MCF-7, and MDA-MB -231 cancer cell lines, where, compounds Hb, III, and IVe demonstrated high to moderate cell proliferation inhibition activity. Compound lib was further assessed for tubulin polymerization inhibition effects due to its high potency, which showed superior suppression compared to the reference drug. It induced cell cycle cessation at the G2/M phase and accumulation of cells in the pre-G1 phase, preventing its mitotic cycle. In addition, compound lib activated caspase-7, mediating apoptosis of HepG2 cells. These findings, along with molecular docking and pharmacophore constructed models, provide a new scaffold of cytotoxic agents targeting tubulin.

Possible improvement of the performance characteristics, reliability and selectivity of solid-contact nitrate ion-selective electrodes (ISE) (SC/NO3−-ISE) is attained by the application of a nitron-nitrate (Nit+/NO3−) ion association complex and inserting multi-walled carbon nanotubes (MWCNTs) as an ion-to-electron transducer between the ion sensing membrane (ISM) and the electronic conductor glassy carbon (GC) substrate. The potentiometric performance of the proposed electrode revealed a Nernstian slope −55.1 ± 2.1 (r² = 0.997) mV/decade in the range from 8.0 × 10−8–1 × 10−2 M with a detection limit of 2.8 × 10−8 (1.7 ng/mL). Selectivity, repeatability and reproducibility of the proposed sensors were considerably improved as compared to the coated disc electrode (GC/NO3−-ISE) without insertion of a MWCNT layer. Short-term potential stability and capacitance of the proposed sensors were tested using a current-reversal chronopotentiometric technique. The potential drift in presence of a MWCNT layer decreased from 167 μVs−1 (i.e., in absence of MWCNTs) to 16.6 μVs−1. In addition, the capacitance was enhanced from 5.99 μF (in absence of MWCNTs) to 60.3 μF (in the presence of MWCNTs). The presented electrodes were successfully applied for nitrate determination in real samples with good accuracy.

A novel single-piece all-solid-state ion-selective electrode (SC/ISE) based on carbon-screen printed is introduced. Polyaniline (PANI) is dissolved in a membrane cocktail that contains the same components used for making a conventional ion-selective polyvinyl chloride (PVC) matrix membrane. The membrane, having the PANI, is directly drop-casted on a carbon substrate (screen-printed-carbon electrode). PANI was added to act as an intermediary between the substrate and the membrane for the charge transfer process. Under non-equilibrium sensing mechanism, the sensors revealed high sensitivity towards 2,4-dichlorophenol (DCP) over the linearity range 0.47 to 13 µM and a detection limit 0.13 µm. The selectivity was measured by the modified separate solution method (MSSM) and showed good selectivity towards 2,4-DCP over the most commonly studied ions. All measurements were done in 30 mm Tris buffer solution at a pH 5.0. Using constant-current chronopotentiometry, the potential drift for the proposed electrodes was checked. Improvement in the potential stability of the SPE was observed after the addition of PANI in the sensing membrane as compared to the corresponding coated-wire electrode (membrane without PANI). The applicability of the sensor has been checked by measuring 2,4-DCP in different water samples and the results were compared with the standard HPLC method.

Novel polycyclic compounds, 1-pyrene-based pyridone derivatives, are synthesized by treatment of pyrenyl acetohydtazide with several arylidenemalononitriles and acetylacetone. Intramolecular cyclization furnishes the functionalized substituted pyridine-2-ones with high yields. Structures of the products are elucidated from the spectral data. Tests on antibacterial activity of the products reveal their high antibacterial effect.

Screen-printed ion-selective electrodes were designed and characterized for the assessment of cyromazine (CYR) pesticide. A novel approach is to design tailor-made specific recognition sites in polymeric membranes using molecularly imprinted polymers for cyromazine (CR) determination (sensor I). Another sensor (sensor II) is the plasticized PVC membrane incorporating cyromazine/tetraphenyl borate ion association complex. The charge-transfer resistance and water layer reached its minimal by incorporating Polyaniline (PANI) solid-contact ISE. The designed electrodes demonstrated Nernstain response over a linear range 1.0 × 10−2–5.2 × 10−6 and 1.0 × 10−2–5.7 × 10−5 M with a detection limit 2.2 × 10−6 and 8.1 × 10−6 M for sensors I and II, respectively. The obtained slopes were 28.1 ± 2.1 (r2 = 0.9999) and 36.4 ± 1.6 (r2 = 0.9991) mV/decade, respectively. The results showed that the proposed electrodes have a fast and stable response, good reproducibility, and applicability for direct measurement of CYR content in commercial pesticide preparations and soil samples sprayed with CYR pesticide. The results obtained from the proposed method are fairly in accordance with those using the standard official method.

Novel biomimetic potentiometric ion-selective electrodes (ISEs) were fabricated and designed for the assessment of aminoacridine (ACR) based on newly synthesized imprinted polymer (MIP) membranes. Thermal polymerization of methacrylic acid (MAA) or acrylamide (AM) as function monomer, aminoacridine as a template and ethylene glycol dimethacrylate (EGDMA) as across-linker, were utilizedto give the molecular recognition part. The membranes of sensors I andII consist of MIP based MAA and AM, respectively, dispersed in a poly(vinyl chloride) membrane plasticized with dioctyl phthalate (DOP) in the ratio of 3.0 wt%, 32.2 wt% and 64.8 wt%, respectively. Sensors III and IV were similarly prepared with added 1.0 wt% tetraphenyl borate (TPB−) as an anionic discriminator. Sensors I and II exhibited near-Nernstian potential response to ACR+ with slopes of 51.2 ± 1.3 and 50.5 ± 1.4 mV/decade in a 0.01 M phosphate buffer of pH 6.0. The linear response coversthe concentration range of 5.2 × 10−6 to 1.0 × 10−3 M with a detection limit of 0.05 and 0.17 μg/mL for sensors I and II, respectively. The performance characteristics of these sensors were evaluated under static and hydrodynamic mode of operations. They were used for quality control assessment of aminoacridine in some pharmaceutical preparations and biological samples.

A new class of pyridopyrimidinone compounds containing different nitrogenous heterocycles were synthesized starting from the key precursor 2-hydrazinyl-5-phenyl-7-(pyridin-3-yl)pyrido[2,3-d]pyrimidin-4(3H)-one via condensation with series of aromatic aldehydes and cyclization using different reagents as ethyl acetoacetate, ethyl cyanoacetate, diethyl malonate, and ammonium isothiocyanate. The bioassay results showed compound 6 to be highly effective towards three human cancer cell lines (HepG2, PC-3, and HCT-116) in vitro with promising activity values (IC50: 0.5 μM) relative to the standard doxorubicin (IC50: 0.6 μM). Kinase inhibitory evaluation of compound 6 displays hopeful inhibitory action against BRAF V600E, EGFR, and PDGFRβ at100 μM. The molecular docking studies supported the initial kinase assay.

A series of novel 2-(pyridin-4-yl)quinazolin-4(3H)-ones bearing different heterocycle cores as potential PI3K inhibitors have been synthesized and evaluated via the MTT assay for their antiproliferative properties against selected HePG-2, MCF-7, and HCT116 cancer cell lines. Among them, compound 9 displayed significant activity against HePG-2 (IC50 = 60.29 ± 1.06 μM) comparable to doxorubicin as a reference anticancer drug (IC50 = 69.60 ± 1.50 μM). Kinase inhibitory assessment of target products against PI3K and docking studies revealed the promising binding affinities which match with the binding mode of the ligand, SW13 towards the active site of PI3K. Therefore, this work represents a promising matrix for developing novel potential anticancer candidates.

A group of trisubstituted pyrazoles containing thiophen, 2-alkyloxypyridine and thieno[2,3-d]pyrimidine heterocycles were synthesized in a study for possible analgesic agents. The desired products were obtained by reaction of 2-(1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazol-4-yemethylene)malononitrile with sulfur in presence of TEA, followed by treatment with different reagents. Newer products were examined for their analgesic properties, among them, analog 7 showed significant analgesic effects in comparison with reference medicines activity.

A new simple potentiometric sensor is developed and presented for sensitive and selective monitoring of dimethylamine (DMA). The sensor incorporates a molecularly imprinted polymer, with a pre-defined specific cavity suitable to accommodate DMA. The molecularly imprinted polymer (MIP) particles were dispersed in an aplasticized poly(vinyl chloride) matrix. The MIP is synthesized by using a template molecule (DMA), a functional monomer (acrylamide, AM), cross-linker (ethylene glycol dimethacrylate, EGDMA) and initiating reagent (benzoylperoxide, BPO). Using Trizma buffer solution (5 mmol L−1, pH 7.1), the sensor exhibits a rapid, stable and linear response for 1.0 × 10−5 to 1.0 × 10−2 mol L−1 DMA+ with a calibration slope of 51.3 ± 0.3 mV decade−1, and a detection limit of 4.6 × 10−6 mol L−1 (0.37 µg mL−1). The electrode exhibited a short response time (10 s) and stable potential readings (± 0.5 mV) for more than 2 months. Potentiometric selectivity measurements of the sensor reveal negligible interferences from most common aliphatic and aromatic amines. High concentration levels (100-fold excess) of many inorganic cations do not interfere. The sensor is successfully used for quantification of low levels of DMA down to 0.5 µg mL–1. Verification of the presented method was carried out after measuring the detection limit, working linearity range, ruggedness of the method, accuracy, precision, repeatability and reproducibility. Under flow-through conditions, the proposed sensor in its tubular form is prepared and introduced in a two-channel flow injection setup for hydrodynamic determination of DMA. The sampling rate is 50–55 samples h–1. The sensor is used to determine DMA in different soil samples with an accuracy range of 97.0–102.8%.

A new series of pyrido[2,3- d ]pyrimidones incorporated pyrazoles and fused triazoles are synthesized and tested in vitro for cytotoxic effect against cancer cell lines: HePG-2, HCT-116, MCF-7, PC-3, and A-549. Their inhibition of protein kinase is assessed. The highest growth inhibitory (IC 50 0.3 µM) effect is determined for one of compounds as compared with doxorubicin (IC 50 0.6 µM). A modeling study is performed for approaching the compounds mode of binding and their similarity with the positive control drugs.

A group of new analogs of 1,3,4-trisubstituted pyrazoles functionalized 2-thioxoimidazolidinones and fused heterocyclic systems are synthesized. Their tests of antimicrobial activity against several bacterial and fungal strains indicated relatively high activity. The composition of the novel products was elucidated from spectroscopic data.

A series of novel 1,3,4-triarylpyrazoles containing different heterocycles has been prepared, characterized and screened for their in vitro antiproliferative activity against HePG-2, MCF-7, PC-3, A-549 and HCT-116 cancer cell lines. The biological results revealed that compound 6 showed the highest anticancer activity so it was subjected to a kinase assay study where it reduced the activity of several protein kinases including AKT1, AKT2, BRAF V600E, EGFR, p38α and PDGFRβ at 100 μM using the radiometric or ADP-Glo assay method. Molecular docking simulation supported the initial kinase assay and suggested a common mode of interaction at the ATP-binding sites of these kinases, which demonstrates that compound 6 is a potential agent for cancer therapy deserving further research.

A series of fused pyrimidine-3-carbonitrile derivatives were synthesized starting from 5-amino-1-(8-hydroxy-7-iodoquinoline-5-sulfonyl)-1 H -pyrazole-3,4-dicarbonitrile, and their structures were determined using spectroscopic and elemental analysis data.