Cancer represents a major global health challenge, contributing to an estimated 19 million new cases annually. While conventional chemotherapeutic approaches continue to advance, target-based therapeutic strategies are increasingly recognized as effective pathways in modern drug development. A prominent biological target in current anticancer research is the selective inhibition of Topoisomerase II alpha (TOP2A). TOP2A, a crucial DNA topoisomerase, is vital for maintaining genomic integrity by mediating the cleavage and re-ligation of double-stranded DNA during essential cellular processes, such as DNA replication and transcription. Inhibiting TOP2A effectively disrupts these processes, leading to cell death. This study employed computer-aided drug design approaches to virtually screen a library of 3000 xanthone derivatives against the TOP2A target, and the results were preliminarily validated through cytotoxicity assays on the A549 and HepG2 cancer cell lines. The computational methods utilized included molecular docking, pharmacological modeling, molecular dynamics simulations, and steered molecular dynamics simulations. The virtual screening identified two highly promising HIT compounds, CID162372098 and CID156619937, that exhibited the most favorable interactions and stability profiles in relation to the TOP2A active site. The experimental results demonstrated that both hit compounds effectively exhibited significant anti-proliferative activities against the HepG2 cell line, with IC50 values of 9.54 ± 0.26 µg mL−1 (CID162372098) and 10.03 ± 0.36 12.69 ± 0.31 µg mL−1 (CID156619937), respectively. Collectively, these findings demonstrate the potential of xanthone-based scaffolds as inhibitors of TOP2A and provide a rational framework for the screening and development of novel anticancer agents.

Phenoxy-linked colchicine derivatives: A structure-based approach toward enhanced selectivity and α-tubulin interaction.

As possible dual VEGFR-2/EGFR inhibitors, a new set of quinazoline-chalcone hybrid compounds (8a-h and 11a-h) was logically developed and synthesized. The synthesized compounds' chemical structures were verified by high-resolution mass spectrometry and 1H and 13C NMR. When all compounds were first tested against the MCF-7 and HepG-2 cancer cell lines at a single concentration (10 μM), several variants showed encouraging growth-inhibitory efficacy. The MTT assay was used to further assess the cytotoxic activity (IC50 values) of the most active candidates (8c, 8h, 11b, 11d, and 11f). Interestingly, the investigated compounds showed poor cytotoxicity against normal WI-38 cells and specific cytotoxicity against cancer cells. The chosen compounds demonstrated greater affinity for VEGFR-2 and efficiently inhibited both EGFR and VEGFR-2 kinases at nanomolar concentrations, as determined by enzyme inhibition studies. When compared to erlotinib (IC50 = 99.5 nM against EGFR) and sorafenib (IC50 = 30.7 nM against VEGFR-2), compound 8h exhibited the strongest dual inhibitory activity, with IC50 values of 97.7 nM against EGFR and 27.8 nM against VEGFR-2, respectively. Molecular docking and molecular dynamics simulations were used to clarify the molecular basis of their activity, and the results confirmed stable binding interactions within both kinases' ATP-binding sites. Additionally, in silico ADME and toxicity tests demonstrated good drug-likeness, pharmacokinetic characteristics, and a satisfactory safety profile. Overall, these results show that quinazoline-chalcone hybrids are effective dual EGFR/VEGFR-2 inhibitors with strong anti-cancer potential.

Synthesis of 4-chloro-N'-(2-cyanoacetyl)benzohydrazide derivatives, cytotoxicity, VEGFR-2/EGFRT790M bioassays and in silico docking/ADMET studies.

Cytotoxic aporphine alkaloids from the roots of Thalictrum baicalense Turcz. ex Regel.

ABSTRACT Breast cancer liver metastasis (BCLM) represents a highly aggressive stage of breast cancer progression, largely driven by abnormal angiogenesis mediated by vascular endothelial growth factor receptor‐2 (VEGFR‐2). Consequently, inhibition of VEGFR‐2 has emerged as an important therapeutic strategy for suppressing tumor angiogenesis and metastatic progression. In the present study, an integrated ligand‐ and structure‐based drug design approach was employed to identify potential VEGFR‐2 inhibitors based on the 1,3,4‐thiadiazole (1,3,4‐TDA) scaffold. Experimentally reported IC 50 data for 1,3,4‐TDA derivatives against MCF‐7 and HepG2 cancer cell lines were used to develop statistically robust GA‐MLR QSAR models exhibiting strong predictive performance (MCF‐7: R 2 = 0.884–0.919, Q 2 LOO = 0.853–0.891; HepG2: R 2 = 0.808–0.815, Q 2 LOO = 0.767–0.771). Mechanistic interpretation of molecular descriptors revealed key structural features influencing VEGFR‐2 inhibitory activity. Subsequent QSAR‐guided virtual screening of a large PubChem library, combined with drug‐likeness filtering, identified several promising candidates with predicted sub‐micromolar potency. Molecular docking studies against VEGFR‐2 (PDB ID: 4ASD) revealed that PubChem CIDs 24647757 and 59818234 were the best binders, exhibiting high LibDock scores (163.017 and 149.055 kcal/mol), strong binding affinities (−11.7 and −12.4 kcal/mol), and forming stable interactions with key residues (ASP1046, CYS1045, and LYS868) in the ATP‐binding pocket. ADMET and toxicity analyses suggested favorable pharmacokinetic properties and improved safety profiles relative to sorafenib. In addition, density functional theory (DFT) calculations supported the favorable electronic properties of the identified hits. Overall, these findings highlight 1,3,4‐TDA derivatives as promising scaffolds for the development of next‐generation VEGFR‐2 inhibitors targeting breast cancer liver metastasis.

The first chiral phosphoric acid-catalyzed formal [6+1] cycloaddition of (2-aminobenzyl)indoles with isatins has been developed, efficiently affording biologically important chiral indoloazepine-based spirooxindoles in high yields (up to 99%) and excellent enantioselectivities (up to 97:3 er). Notably, this novel class of chiral indoloazepine-based spirooxindoles exhibits potent cytotoxicity against human liver cancer cell line HepG2.

This study aimed to synthesize new α-aminophosphonate derivatives based on 2-(thiophen-2-yl)-1H-indole-3-carbaldehyde and evaluate their anticancer, antimicrobial, and drug-likeness properties supported by molecular docking studies. A series of α-aminophosphonates (5a-h) were synthesized using an optimized zinc chloride (ZnCl2)-catalyzed reaction. The synthesized compounds were characterized by standard spectroscopic techniques. Antiproliferative activity was evaluated using MTT assays against MCF7 and HepG2 cancer cell lines. Antimicrobial activity was assessed against Gram-positive and Gram-negative bacteria and fungi. Molecular docking and ADMET analyses were also performed. Compounds 5b and 5e exhibited potent cytotoxic activity against MCF7 cells with IC50 values of 9.5 and 9.2 µM, comparable to doxorubicin (9.4 µM). All compounds demonstrated lower cytotoxicity toward HepG2 cells. Compound 5d showed the strongest antimicrobial activity with MIC values of 10-20 µg/mL, surpassing gentamicin. Molecular docking has revealed key hydrogen-bonding and π-interactions supporting dual biological activities. ADMET profiling indicated favorable drug-like properties for compounds 5a-5e. The synthesized α-aminophosphonates represent promising candidates for future development as dual anticancer and antimicrobial agents.

Quinazolinone derivatives possess a privileged scaffold with variable pharmacological activities. This study conducted an in vitro evaluation of the pyrazine-linked quinazolinone sulfonamide derivative (PQS) to assess its anticancer activity, following confirmation of its safety in a normal cell line. Results revealed that PQS has a noteworthy cytotoxic effect on HepG-2 and HeLa cells, indicating its potential anticancer activity. Additionally, PQS is quite safe on normal Vero cells. Furthermore, in vivo biological activity of PQS was evaluated for its radioprotective propertiesin (5Gy) irradiated mice. PQS showed mitigation of gamma radiation-induced oxidative stress, verified by the decline in MDA, ROS and NO levels, while GSH levels and GST activities were improved in kidney tissues. The apoptotic pathway was also assessed, where weak expression of caspase-3 and Bcl2-associated X protein (Bax) was noticed paired with higher expression of B-cell lymphoma 2 (Bcl2) after PQS treatment in irradiated mice. These results were confirmed by histopathological examination of kidney tissues. Besides, in-silico ADME studies revealed that compound PQS showed drug-like properties, confirmed by its physicochemical and pharmacokinetic properties. In conclusion, the results of the present study demonstrated that PQS has dual activity as a potential anticancer on HepG-2 and HeLa cancer cell lines and radio-protective activity through its anti-apoptotic and antioxidant action in the in vivo study.

Ephedra alata is a medicinal plant known for its rich composition of bioactive compounds and therapeutic properties. This study explores its phytochemical profile, antioxidant capacity, and potential anticancer effects. LC-MS analysis identified a variety of flavonoids and glycosylated derivatives, with quercetin 3-D-galactoside (28.49%) and 3,3’,4,4’,5,7-pentahydroxy-6-methoxyflavanonol-3-O-glucoside-5-O-glucuronic acid (10.74%) as the most abundant compounds. These flavonoids are recognized for their strong antioxidant and anticancer properties. The extract exhibited significant metal chelation activity, assessed using an EDTA-based calibration curve, indicating its potential to combat oxidative stress. Additionally, the ORAC assay confirmed a high free radical-scavenging ability, primarily linked to the presence of flavonoids such as quercetin, rutin, and kaempferol.To evaluate its anticancer potential, the methanolic extract was tested on liver cancer cell lines (Huh-7 and HepG2) using a WST-1 assay. The results showed a dose-dependent reduction in cell viability, with HepG2 cells displaying greater sensitivity than Huh-7 cells. Cytotoxicity extract’s IC₅₀ values exceeded 100 µg/mL, indicating weak, cytotoxicity, the findings suggest that its bioactive compounds may play a role in inducing apoptosis and regulating oxidative stress in cancer cells. These results highlight Ephedra alata as a promising natural source of bioactive compounds with antioxidant potential, supporting further studies to explore its therapeutic applications.

Controlled drug delivery from stimuli-responsive drug carriers offers effective therapeutic potential; however, the precise assessment of the release kinetics and pharmacodynamic (PD) behavior remains challenging. In this work, surface-enhanced Raman spectroscopy (SERS) is used to quantify the spectinomycin-copper (SPM-Cu(II)) complex released in vitro into the human blood serum. Silver nanoparticles (AgNPs) are prepared by the chemical reduction method as the active SERS substrate. The SPM-Cu(II) complex loaded on the stimuli-responsive PVA/AgO hydrogel is released into the blood serum, and the release kinetics and in vitro pharmacodynamics are studied at different time points up to 36 hours (1 h, 4 h, 8 h, 12 h, 16 h, 20 h, 24 h, 28 h, 32 h and 36 h). For multivariate data analysis, principal component analysis (PCA) is used to qualitatively study the intensity-based variability, partial least squares regression (PLSR) is used to quantify the SPM-Cu(II) complex release kinetics and hierarchical cluster analysis (HCA) is used to determine spectral variability and classify temporal release profiles. The release kinetics is additionally validated by UV-vis spectroscopic quantification and compared with that of the SPM-Cu(II) complex released in a phosphate buffer solution of pH 7.4 at 37 °C. The in vitro release kinetics is determined using four kinetic models: zero-order, first-order, Higuchi, and Korsmeyer-Peppas models. It is shown by mathematical fitting that the release is dominated by Higuchi (R2 = 0.934 in serum and 0.944 in PBS) and Korsmeyer-Peppas models (n = 0.463, which is Fickian diffusion), indicating that the release is diffusion-controlled. The pharmacodynamic potential of the released SPM-Cu(II) complex in blood serum is evaluated systematically by establishing its antibacterial activity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) and by conducting biofilm assays against Pseudomonas aeruginosa and Enterococcus faecalis. The cytotoxicity against the human liver cancer cell line (HepG2) and hemolytic analysis are also performed to validate the release kinetics in blood serum. The results indicate the improved antibacterial and biocompatible properties of SPM-Cu(II) released in the blood serum from the PVA/AgO hydrogel.

Deciphering the detailed crystallographic structure of biologically synthesized nano-silver: Antioxidant potential, antimicrobial efficacy and anticancer properties against HepG2 cancer cell line with accentuation to apoptosis and ROS generation

Phytochemical investigation on the 75% EtOH fraction of the green walnut husks of Juglans mandshurica Maxim led to the isolation of four new naphthalene glycosides, Juglophenoside I (1), Juglophenoside II (2), Juglanoside R (3), juglanbioside F (4) as well as 13 known naphthalene compounds (5-17). Structural elucidation of all compounds was carried out by spectroscopic methods such as 1D and 2D NMR spectroscopy (1H-1HCOSY, HSQC, and HMBC), and high resolution mass spectrometry. Moreover the compounds were evaluated for their cytotoxic activities against three cancer cell lines BGC-823, Hela, and HepG-2. Results showed that compounds 1 and 13 had inhibitory effects on HeLa, BGC-823 and Hep-G2 cells, with IC50 values of (58.57 ± 0.74), (62.83 ± 0.91), (68.14 ± 0.72) µM and (61.17 ± 1.74), (67.24 ± 2.24), (56.35 ± 0.55) µM.

Multi-target enzyme inhibition represents a promising strategy to overcome resistance and improve therapeutic outcomes in cancer therapy. In this study, a new series of 1,3,4-oxadiazole derivatives was synthesized and evaluated for cytotoxic and multi-target anticancer activities. Several compounds demonstrated potent antiproliferative effects against HepG2, MCF-7, and HCT-116 cancer cell lines with reduced toxicity toward WI-38 normal fibroblasts. Among them, compounds 1, 9, 12, and 13 emerged as the most promising candidates, showing strong cytotoxicity and favorable selectivity profiles. Enzyme inhibition assays confirmed their ability to target key oncogenic enzymes, including wild-type and mutant (T790M) EGFR, telomerase, and thymidylate synthase. Mechanistic studies revealed that compound 12 induced G1 phase cell cycle arrest and promoted apoptosis in HepG2 cells with minimal necrosis. Molecular docking, molecular dynamics simulations, and MM-GBSA analyses supported stable binding of the active compounds within the catalytic sites of the investigated enzymes. Overall, these findings identify compounds 1, 9, 12, and 13 as promising multi-target anticancer leads warranting further optimization and development.

In this study, 2-(4-methylpiperidin-1-yl)acetohydrazide was condensed with a series of substituted benzaldehydes to afford a library of piperidine-based hydrazones, which were subsequently complexed with K₂PtCl₄ and K₂PdCl₄ to yield the corresponding Pt(II) and Pd(II) complexes. The structures of molecules were elucidated by spectral methods and elemental analysis. The in vitro anticancer potential of the compounds was evaluated through cytotoxicity, wound-healing/migration, and RT-qPCR assays in A549 (lung) and HepG2 (hepatocellular) cancer cell lines. In the cytotoxicity studies, compound 3lPd exhibited the highest activity in A549 cells (IC₅₀ = 61.25 ± 0.03 µM), while ligand 3b and complex 3nPt showed the most pronounced effects in HepG2 cells (IC₅₀ = 77.96 ± 0.05 and 77.01 ± 0.02 µM, respectively). The most active compounds were further tested in wound-healing assays, where 3lPd almost completely inhibited A549 cell migration at 24 and 48 h, whereas the reference drug cisplatin induced only partial inhibition. Consistent with these findings, RT-qPCR analysis revealed that in A549 cells, 3lPd markedly suppressed MYC expression and reduced p53 levels to an extent comparable to cisplatin. In HepG2 cells, 3nPt decreased p53 expression, while L3b uniquely upregulated p53 and maintained MYC expression near control levels. In silico studies were performed to investigate their interactions with p53, GAPDH, and c-MYC proteins. Overall, these results suggest that piperidine-bearing hydrazones and their Pt(II)/Pd(II) complexes represent promising scaffolds for the development of novel anticancer agents.

Biogenic synthesis of nascent and nitrogen doped carbon dots from Cordia dichotoma G. Forst: Morphological, optical and therapeutic insights for HepG2 cancer cell line therapy

Moringa oleifera, a nutrient-rich medicinal plant, has garnered growing scientific interest due to its diverse pharmacological properties. In this study, spectroscopic analysis, coupled with cytotoxic, antiviral, and antioxidant properties testing, was followed by gene expression analysis of various fractionated Moringa oleifera extracts to assess their potential biomedical applications. Ethanolic leaf extract was fractionated using solvents with increasing polarity (hexane, methylene chloride, ethyl acetate, and butanol). Cytotoxicity was tested against multiple cancer cell lines and normal cells, while antiviral activity was assessed against HAV ( Hepatitis A virus) and HSV-1/2 (Herpes simplex virus type 1/type 2). Antioxidant capacity was evaluated using DPPH assays. Gene expression of BAX and BCL-2 was analyzed by qRT-PCR to understand apoptotic pathways. Chemical profiling was performed using LC–MS/MS and GC–MS. The hexane fraction showed potent cytotoxicity against cancer cell lines MCF-7 (breast carcinoma) and HepG-2 (hepatocellular carcinoma), with low toxicity to normal PBMCs (normal human primary peripheral blood mononuclear cells). The butanol fraction displayed strong antiviral activity, particularly against HAV and HSV strains, while the ethyl acetate fraction exhibited the strongest antioxidant activity. The pro-apoptotic BAX gene was upregulated while the anti-apoptotic BCL-2 gene was downregulated, according to gene expression analysis. Metabolomic profiling identified over 60 bioactive compounds, including phenolic acids, flavonoids, and terpenoids, which were consistent with the observed biological activities. These findings characterize Moringa oleifera as a rich source of multifunctional bioactive compounds and provide a preliminary in vitro foundation for its potential application in selective anticancer and antiviral therapies.

New pyrazole-based analogues coupled with a pyrazine core were successfully synthesized, using 2-(4-acetylphenyl)aminopyrazine (1) as starting material, and their structures were established from the NMR, IR, and mass spectroscopic analyses. The DFT computations showed that these hybrids adopted nonplanar geometries and comparable HOMO-LUMO features. Moreover, the frontier orbital energies have been exploited in the evaluation of principal reactivity descriptors, which designated the hybrid 3b to have the lowest electronegativity and hardness values. In addition, the cytotoxic activity was investigated against HepG2, HT-29, and MCF-7 cancer cell lines, as well as the normal WI-38 cells, using Dasatinib as the reference drug. Analogue 3c revealed the strongest anticancer performance, with IC₅₀ values ranging from 7.48 ± 0.18 to 11.20 ± 0.01 µM. Antiviral activity against H5N1 was also examined using a plaque reduction assay, where compounds 3c and 7c achieved remarkable inhibition levels of 100% and 88%, respectively, at non-toxic concentrations. Moreover, the molecular docking studies supported their potential by revealing favorable interactions with the 3Q3X protein target. The SwissADME pharmacokinetic predictions indicated that all compounds exhibit drug-like properties, including high gastrointestinal absorption and full compliance with Lipinski’s rule of five. Accordingly, the synthesized pyrazine-pyrazole hybrids represent promising scaffolds for future multi-functional anticancer and antiviral drug development.

New pyrazole-based compounds were synthesized via a one-pot three-component reaction including 5-methyl-2,4-dihydro-3H-pyrazol-3-one, 2,6-dichlorobenzaldehyde, and various active methylene compounds. The chemical structures of these compounds were fully elucidated using various elemental and spectral analyses. The synthesized compounds were evaluated for their antiproliferative activity against HepG2 (liver), MCF-7 (breast), and HCT-116 (colon) human cancer cell lines, alongside normal WI-38 fibroblasts. Several derivatives displayed moderate-to-good cytotoxic activity with varying degrees of selectivity. In particular, compound 6 exhibited the highest potency (HepG2 IC50 = 6.17 µM; MCF-7 IC50 = 8.65 µM), with selectivity (SI = 4.1) higher than that of doxorubicin (SI = 1.4). In silico ADME studies predicted favorable drug-like properties and good oral bioavailability for all compounds, with limited blood–brain barrier penetration. Molecular docking against KIT, CDK2, and c-Met kinases revealed consistent multi-kinase binding for the most active derivatives, correlating well with their in vitro antiproliferative effects. Density functional theory calculations further supported these findings by elucidating electronic features relevant to molecular reactivity and ligand–protein interactions. Overall, this study identifies a promising pyranopyrazole-based scaffold for further optimization toward selective multi-kinase anticancer agents.

The genus Psiadia (Asteraceae), widely distributed in Madagascar and the Mascarene Islands (Mauritius, La Réunion, Rodrigues), is traditionally used to treat bronchitis, asthma, colds, abdominal pain, and other inflammatory disorders. However, few studies have scientifically validated these traditional medicinal uses. To assess P. dentata as a valuable source of bioactive natural products, a combined 1H NMR-based metabolomic, molecular networking, and phytochemical study was conducted. Multivariate analysis (PLS-DA) of crude extracts from Psiadia species collected on Reunion Island enabled rapid discrimination of active extracts from P. dentata and revealed two methoxylated flavonoids and one coumarin as metabolites correlated with its antiplasmodial and anti-inflammatory activities. Additionally, UHPLC-DAD-ESI-QTOF-MS/MS molecular networking approach enabled detailed chemical profiling of this species, allowing the annotation of 25 compounds (1-25) in this species. Subsequent phytochemical investigation of P. dentata leaves led to the isolation and identification of 25 metabolites, including nine new diterpenes (26-34), one new coumarin (35), and 15 known compounds (1-8, 11, 18, 19 and 36-39) from the diterpenoid, flavonoid, and coumarin families. The structures of the new compounds were elucidated using spectroscopic methods, including extensive 1D and 2D NMR and HRESIMS analyses. Biological evaluation of the isolated compounds showed that compounds 1, 7, 26 and 27 showed antiplasmodial activity against Plasmodium falciparum (3D7 strain, IC50 = 7.25-13.46 μM). Compounds 7, 26, 27, 31 and 32 inhibited nitric oxide production (IC50 = 0.87-27.71 μM), indicating potential anti-inflammatory effects. Only compound 1 displayed moderate cytotoxicity against HepG2 and HT29 cancer cell lines (IC50 = 25.67 and 18.35 μM, respectively).