Search Results (200)

Atopic dermatitis (AD) is a chronic, multifactorial inflammatory skin disease characterized by persistent pruritus, immune system dysregulation, and an increased expression of cyclooxygenase-2 (COX-2), an enzyme that plays a central role in the production of prostaglandins and the promotion of inflammatory responses. In this study, we employed a comprehensive computational pipeline to identify phytocompounds capable of inhibiting COX-2 activity, offering an alternative to traditional non-steroidal anti-inflammatory drugs. The African and Traditional Chinese Medicine natural product databases were subjected to molecular screening, which identified six top compounds, namely, Tophit1 (−16.528 kcal/mol), Tophit2 (−10.879 kcal/mol), Tophit3 (−9.760 kcal/mol), Tophit4 (−9.752 kcal/mol), Tophit5 (−8.742 kcal/mol), and Tophit6 (−8.098 kcal/mol), with stronger binding affinities to COX-2 than the control drug rofecoxib (−7.305 kcal/mol). Molecular dynamics simulations over 200 ns, combined with MM/GBSA binding free energy calculations, consistently identified Tophit1 and Tophit2 as the most stable complexes, exhibiting exceptional structural integrity and a strong binding affinity to the target protein. ADMET profiling via SwissADME and pkCSM validated the drug-likeness, oral bioavailability, and safety of the lead compounds, with no Lipinski rule violations and favorable pharmacokinetic and toxicity profiles. These findings underscore the therapeutic potential of the selected phytocompounds as novel COX-2 inhibitors for the management of atopic-prone skin and warrant further experimental validation. Full article

Foeniculum vulgare Mill. (Apiaceae) is an aromatic medicinal plant known for its anti-inflammatory, antispasmodic, antiseptic, carminative, diuretic, and analgesic properties. This study aimed to investigate the effects of F. vulgare essential oil (FVEO; 25, 150, and 300 μL/L) on the cognitive performance and brain oxidative stress in a scopolamine (SCOP; 100 μM)-induced zebrafish model of cognitive impairment. Additionally, the pharmacokinetic properties and bioactivity profiles of the main FVEO constituents were predicted to be used in silico tools, including SwissADME, pkCSM, PASS online, and ADMETlab 2.0. Behavioral assays, novel tank diving test (NTT), Y-maze, and novel object recognition (NOR) test, were used to evaluate anxiety-like behavior, spatial memory, and recognition memory, respectively. Biochemical assessments of acetylcholinesterase (AChE) activity and oxidative stress biomarkers were also conducted. The results demonstrated that FVEO significantly improved cognitive performance in SCOP-treated zebrafish, normalized AChE activity, and reduced oxidative stress in the brain. These findings suggest the therapeutic potential of FVEO in ameliorating memory impairment and oxidative damage associated with neurodegenerative disorders such as Alzheimer’s disease (AD). Full article

Background: Shirakiopsis indica (Willd.) (Family: Euphorbiaceae), a mangrove species found in the Asian region, is a popular folkloric plant. Locally, the plant is traditionally used to treat various types of ailments, especially for pain relief. Therefore, the current study investigates the neuropharmacological, antipyretic, thrombolytic, and anthelmintic properties of the S. indica fruit methanolic extract (SIF-ME). Methods: The neuropharmacological activity was evaluated using several bioactive assays, and the antipyretic effect was investigated using the yeast-induced pyrexia method, both in Swiss albino mice models. Human blood clot lysis was employed to assess thrombolytic activity, while in vitro anthelmintic characteristics were tested on Tubifex tubifex. Insights into phytochemicals from SIF-ME have also been reported from a literature review, which were further subjected to molecular docking, pass prediction, and ADME/T analysis and validated the wet-lab outcomes. Results: In the elevated plus maze test, SIF-ME at 400 mg/kg demonstrated significant anxiolytic effects (200.16 ± 1.76 s in the open arms, p < 0.001). SIF-ME-treated mice exhibited increased head dipping behavior and spent a longer time in the light box, confirming strong anxiolytic activity in the hole board and light–dark box tests, respectively. It (400 mg/kg) also significantly reduced depressive behavior during forced swimming and tail suspension tests (98.2 ± 3.83 s and 126.33 ± 1.20 s, respectively). The extract induced strong locomotor activity, causing mice’s mobility to gradually decrease over time in the open field and hole cross tests. The antipyretic effect of SIF-ME (400 mg/kg) was minimal using the yeast-induced pyrexia method, while it (100 μg/mL) killed T. tubifex in 69.33 ± 2.51 min, indicating a substantial anthelmintic action. SIF-ME significantly reduced blood clots by 67.74% (p < 0.001), compared to the control group’s 5.56%. The above findings have also been predicted by in silico molecular docking studies. According to the molecular docking studies, the extract’s constituents have binding affinities ranging from 0 to −10.2 kcal/mol for a variety of human target receptors, indicating possible pharmacological activity. Conclusions: These findings indicate that SIF-ME could serve as a promising natural source of compounds with neuropharmacological, anthelmintic, thrombolytic, and antipyretic properties. Full article

Background: Ovarian cancer is a major challenge in oncology due to high mortality rates, especially in advanced stages, despite current therapeutic approaches relying on chemotherapy and surgery. The search for novel therapeutic strategies is driven by the need for more effective treatments. This study focuses on novel xanthone derivatives modified with a morpholine ring, aiming to improve anticancer efficacy. Methods: In silico studies were conducted using ProTox III and SwissADME databases to assess the toxicity and ADME properties of the synthesized compounds. Molecular changes in cellular stress-related genes were investigated through qPCR in two ovarian cancer cell lines (TOV-21G and SKOV-3) following treatment with the compounds. Results: In silico analyses predicted high gastrointestinal absorption and blood–brain barrier permeability for the derivatives. Compounds exhibited varying toxicity and metabolic profiles. qPCR revealed significant alterations in genes related to antioxidant enzymes, molecular chaperones, and xenobiotic metabolism, indicating potential mechanisms of action and cellular responses to the compounds. Conclusions: The study demonstrates the potential of novel xanthone derivatives as promising candidates for ovarian cancer therapy, with implications for enhancing therapeutic efficacy and addressing drug resistance. Further research is warranted to elucidate the precise mechanisms underlying the observed effects and to develop tailored treatment strategies leveraging these agents. Full article

Background: Malaria remains a significant global health burden, particularly in sub-Saharan Africa, accounting for high rates of illness and death. The growing resistance to frontline antimalarial therapies underscores the urgent need for novel drug targets and therapeutics. Bromodomain-containing proteins, which regulate gene expression through chromatin remodeling, have gained attention as potential targets. Plasmodium falciparum bromodomain protein 1 (PfBDP1), a 55 kDa nuclear protein, plays a key role in recognizing acetylated lysine residues and facilitating transcription during parasite development. Methods: This study investigated ex vivo PfBDP1 gene mutations and identified potential small molecule inhibitors using computational approaches. Malaria-positive blood samples were collected. Genomic DNA was extracted, assessed for quality, and amplified using PfBDP1-specific primers. DNA sequencing and alignment were performed to determine single-nucleotide polymorphism (SNP). Structural modeling used the PfBDP1 crystal structure (PDB ID: 7M97), and active site identification was conducted using CASTp 3.0. Virtual screening and pharmacophore modeling were performed using Pharmit and AutoDock Vina, followed by ADME/toxicity evaluations with SwissADME, OSIRIS, and Discovery Studio. GROMACS was used for 100 ns molecular dynamics simulations. Results: The malaria prevalence rate stood at 12.24%, and the sample size was 165. Sequencing results revealed conserved PfBDP1 gene sequences compared to the 3D7 reference strain. Virtual screening identified nine lead compounds with binding affinities ranging from −9.8 to −10.7 kcal/mol. Of these, CHEMBL2216838 had a binding affinity of −9.9 kcal/mol, with post-screening predictions of favorable drug-likeness (8.60), a high drug score (0.78), superior pharmacokinetics, and a low toxicity profile compared to chloroquine. Molecular dynamics simulations confirmed its stable interaction within the PfBDP1 active site. Conclusions: Overall, this study makes a significant contribution to the ongoing search for novel antimalarial drug targets by providing both molecular and computational evidence for PfBDP1 as a promising therapeutic target. The prediction of CHEMBL2216838 as a lead compound with favorable binding affinity, drug-likeness, and safety profile, surpassing those of existing drugs like chloroquine, sets the stage for preclinical validation and further structure-based drug design efforts. These findings are supported by prior experimental evidence showing significant parasite inhibition and gene suppression capability of predicted hits. Full article

Background/Objectives: Since the emergence of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the discovery of compounds with antiviral potential from medicinal plants has been extensively researched. This study aimed to investigate plant metabolites with in vitro inhibitory potential against SARS-CoV-2 targets, including 3CL_pro, PL_pro, Spike protein, and RdRp. Methods: A systematic review was conducted following PRISMA guidelines, with literature searches performed in six electronic databases (Scielo, ScienceDirect, Scopus, Springer, Web of Science, and PubMed) from January 2020 to February 2024. Computational analyses using SwissADME, pkCSM, ADMETlab, ProTox3, Toxtree, and DataWarrior were performed to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles as well as other medicinal chemistry parameters of these compounds. Results: A total of 330 plant-derived compounds with inhibitory activities against the proposed targets were identified, with compounds showing IC₅₀ values as low as 0.01 μM. Our findings suggest that several plant metabolites exhibit significant in vitro inhibition of SARS-CoV-2 targets; however, few molecules exhibit drug development viability without further adjustments. Additionally, after these evaluations, two phenolic acids, salvianic acid A and protocatechuic acid methyl ester, stood out for their potential as candidates for developing antiviral therapies, with IC₅₀ values of 2.15 μM against 3CL_pro and 3.76 μM against PL_pro; respectively; and satisfactory in silico drug-likeness and ADMET profiles. Conclusions: These results reinforce the importance of plant metabolites as potential targets for antiviral drug discovery. Full article

Background/Objectives: The current need for new antibacterial compounds that target non-classical pathways is highlighted by the emergence of multidrug-resistant Klebsiella pneumoniae. In the development of antibiotics, DNA adenine methyltransferase (Dam), a key regulator of bacterial gene expression and pathogenicity, is still underutilized. Epoxy-functionalized analogues of isatin derivatives have not been adequately investigated for their antibacterial activity, particularly as Dam inhibitors. In the pursuit of antimicrobial agents, this study synthesized an epoxy-functionalized isatin derivative (L3) using a one-pot reaction. The compound was characterized using FT-IR, ¹H-NMR, ¹³C-NMR, HR-MS, and UV–Vis spectroscopy. Methods: In silico evaluation performed by using ADMETlab3 and SwissADME. While molecular docking studies were achieved by AutoDock and Vina to find L3’s interaction with potential antibacterial target (Dam protein in K. pneumoniae). In addition, the antibacterial potential of L3 was evaluated using minimum inhibitory concentration (MIC) assays against Bacillus cereus, Bacillus pumilus, Escherichia coli, and K. pneumoniae. Results: Among these, L3 exhibited potential inhibitory activity against K. pneumoniae, with a MIC value of 93.75 μg/mL. In silico evaluations confirmed L3’s favorable drug-like properties, including potential oral bioavailability, blood–brain barrier (BBB) permeability, and low plasma protein binding (PPB). The compound satisfied Lipinski’s and other drug-likeness rules as well as getting a quantitative estimate of drug-likeness (QED) score of 0.52. Here, a homology model of Dam protein in K. pneumoniae was generated using the SWISS-MODEL server and validated using computational tools. Targeted docking analysis revealed that L3 exhibited significant potential binding affinity against Dam protein, with binding energies of −6.4 kcal/mol and −4.85 kcal/mol, as determined by Vina and AutoDock, respectively. The associated inhibition constant was calculated as 280.35 µM. Further interaction analysis identified the formation of hydrogen bonds with TRP7 and PHE32, along with Van der Waals’ interactions involving GLY9, ASP51, and ASP179. Conclusions: These findings highlight L3 as a promising scaffold for antimicrobial drug development, particularly in targeting Dam protein in K. pneumoniae. Furthermore, the ADMET profiling and physicochemical properties of L3 support its potential as a drug-like candidate. Full article

Background: The need for innovative therapeutic strategies to enhance patient outcomes has increased due to the rise in bacterial co-infections associated with COVID-19. Methods: In this study, ten hybrid compounds were synthesized by combining two known pharmaceutical scaffolds to enhance antibacterial activity and overcome resistance mechanisms. The synthesized compounds were evaluated for their antibacterial activity against five Gram-negative and seven Gram-positive bacterial strains. In silico pharmacokinetic and drug-likeness properties of selected active compounds (12–16, 19, 21, and 23) were predicted using the SwissADME web tool. Results: Compounds 12–16, 19, 21, and 23 demonstrated significant antibacterial activity, with compound 16 (a ciprofloxacin-containing hybrid) exhibiting the most potent effect, showing a minimum inhibitory concentration (MIC) of 7.8125 µg/mL against all tested bacterial strains. The in silico analysis revealed favorable pharmacokinetic profiles, drug-likeness, lipophilicity, and water solubility of most hybrid compounds. Discussion: The synthesized hybrid compounds exhibited enhanced antibacterial activity and desirable pharmacokinetic properties, particularly compound 16. These findings suggest the potential of these molecules in combating bacterial pathogens, especially those implicated in co-infections in COVID-19 infections. Conclusions: The study presents promising hybrid antibacterial agents with potential application as adjunct therapies for treating COVID-19-associated bacterial co-infections. Further investigation is needed, which may lead to effective treatments for managing secondary bacterial infections in viral disease contexts. Full article

Withanolides are a class of naturally occurring C-28 ergostane steroidal lactones with an abundance of biological activities, and their members are promising candidates for antineoplastic drug development. The ADMET properties of withanolides are still largely unknown, and in silico predictions can play a crucial role highlighting these characteristics for drug development, shortening time and resources spent on the development of a drug lead. In this work, ADMET properties of promising antitumoral withanolides were assessed. Each chemical structure was submitted to the prediction tools: SwissADME, pkCSM–pharmacokinetics, admetSAR v2.0, and Molinspiration Cheminformatics. The results indicate a good gastrointestinal absorption rate, inability to cross the blood–brain barrier, CYP3A4 metabolization, without inhibition of other P450 cytochromes, high interaction with nuclear receptors, and a low toxicity. It was also predicted for the inhibition of pharmacokinetics transporters and some ecotoxicity. This demonstrates a viability for oral drug development, with low probabilities of side effects. Full article

Cisplatin (CIS) is a widely used chemotherapeutic agent that is highly effective against various cancers. However, its clinical application is frequently limited by its substantial nephrotoxic side effects. The gastrin-releasing peptide receptor (GRPR), a critical regulator in inflammatory diseases, has been identified as a promising therapeutic target. Our previous studies have demonstrated that the GRPR antagonists PD176252 and RH-1402 can mitigate CIS-induced nephrotoxicity through anti-inflammatory mechanisms. Based on these findings, we designed and synthesized a series of 2-arylpropanoic acid-L-tryptophan derivatives to enhance the therapeutic effects. Among these compounds, 3m exhibited superior renal protection by significantly improving mouse renal tubular epithelial cell (mRTEC) viability from 50.2 ± 2.6% to 80.5 ± 3.9%, surpassing PD176252 (70.8 ± 1.4%) and RH-1402 (73.9 ± 3.7%). Moreover, compound 3m markedly reduced the expression of kidney injury molecule-1 (KIM-1) and inflammatory cytokines [Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Monocyte Chemoattractant Protein-1 (MCP-1)]. Finally, molecular docking results revealed that 3m exhibited a high binding affinity for GRPR. Computational predictions using SwissADME further indicated that 3m possesses favorable drug-like properties, thereby supporting its potential as a promising candidate for mitigating CIS-induced nephrotoxicity. Full article

Background/Objectives:Bougainvillea x buttiana is used in traditional Mexican medicine to treat various diseases. Previous studies have demonstrated its anti-inflammatory properties, which are associated with its chemical composition. This study evaluated the effect of ethanol concentration on the yield and anti-inflammatory activity of its extracts. Additionally, an in silico analysis of the plant’s previously identified phytochemicals was conducted. Methods: Four extracts of B. x buttiana (var. Rose) (labeled as BxbREE) were prepared with increasing concentrations of ethanol (0%, 50%, 80%, and 100%). Their anti-inflammatory activity was assessed using different in vitro assays. The in silico prediction, performed with SwissADME, included the physicochemical, pharmacokinetic, and drug-like properties of the compounds. Results: The findings indicated that varying the ethanol concentration in the preparations of BxbREE-0%, BxbREE-50%, BxbREE-80%, and BxbREE-100% significantly impacted the extraction yield, with BxbREE-0% and BxbREE-50% exhibiting the highest recovery. All four extracts demonstrated significant anti-inflammatory activity, with BxbREE-50% and BxbREE-80% showing the most important effects on the denaturation of bovine serum albumin (BSA) and trypsin, inhibition of pro-inflammatory enzymes (cyclooxygenase and phospholipase A2), and increased stability of the erythrocyte membrane. The in silico analysis revealed that most phytochemicals identified in the extracts had good drug-likeness and bioavailability for oral administration and an adequate ADME profile. Conclusions: These findings reaffirm the anti-inflammatory potential of B. x buttiana (var. Rose) ethanolic extracts and the favorable pharmacokinetic and pharmacodynamic properties of its phytochemicals. Further structural exploration of the interactions of these bioactive compounds could contribute to the design of new drugs. Full article

Background/Objectives: Haloxylon griffithii is a medicinal plant possessing therapeutic effects in disorders associated with the gastrointestinal (GIT) system. This research aims to study the pharmacological activity of Haloxylon griffithii in a multidimensional manner, involving phytochemistry screening and in vitro and in vivo experiments. Methods: The whole dried plant was extracted with 80% methanol and further fractionation using solvents of increasing polarity. GC-MS analysis was performed on the crude extract to discover volatile compounds. The spasmolytic/spasmogenic effect was assessed in isolated rabbit jejunum using spontaneous and K⁺-induced contractions, as well as contractions induced by increasing concentrations of calcium ions in depolarized tissue. Antidiarrheal activity was evaluated in Swiss albino rats/mice (n = 6/group) using castor oil-induced diarrhea and peristaltic index models. In silico ADMET screening was conducted via SwissADME and pkCSM. Results: The GC-MS profiling of H. griffithii revealed the presence of 59 phytochemicals and a rare azulene derivative and constituents, including α-santonin and hexadecanoic acid esters, with favorable pharmacokinetic profiles, as predicted using SwissADME and pkCSM computational tools. The in vitro and in vivo experiments revealed the significant calcium channel blocking activity in non-polar fractions (n-hexane and ethyl acetate), while the polar extracts (ethanolic, aqueous) exhibited cholinergic effects, indicating a dual mode of action. Conclusions: This was a first-time demonstration of both antidiarrheal and smooth muscle-relaxant activity in H. griffithii, supported by GC-MS profiling and pharmacological assay. The findings lend scientific credibility to the traditional use of the plant in community healthcare, while also reinforcing the need for further pharmacological and clinical studies to explore its potential in drug development. Full article

Cardiovascular disease remains a leading cause of morbidity and mortality worldwide, frequently arising from platelet hyperactivation and subsequent thrombus formation. Although conventional antiplatelet therapies are available, challenges, such as drug resistance and bleeding complications, require the development of novel agents. In this study, dihydrogeodin (DHG) was isolated from Fennellia flavipes and evaluated using platelets derived from Sprague–Dawley rats. Platelet aggregation induced by collagen, adenosine diphosphate, or thrombin was assessed by light transmission aggregometry; DHG significantly reduced aggregation in a dose-dependent manner. Further assays demonstrated that DHG suppressed intracellular calcium mobilization, adenosine triphosphate release, and integrin αIIbβ₃-dependent fibrinogen binding, thereby impairing clot retraction. Western blot analysis revealed that DHG reduced the phosphorylation of mitogen-activated protein kinases (ERK, JNK, p38) and PI3K/Akt, indicating inhibition across multiple platelet-signaling pathways. Additionally, SwissADME-assisted pharmacokinetics predicted favorable properties without violations of the Lipinski (Pfizer) filter, Muegge (Bayer) filter, Ghose filter, Veber filter, and Egan filter, and network pharmacology revealed inhibition of calcium and MAPK pathways. These results highlight the potential of DHG as a novel antiplatelet agent with broad-spectrum activity and promising drug-like characteristics. Further studies are warranted to assess its therapeutic window, safety profile, and potential for synergistic use with existing antiplatelet drugs. Full article

Substantial in vitro experimental data have been produced about the safety, antioxidant, neuro- and hepatoprotective effects of a series of recently synthesized N-pyrrolyl hydrazide-hydrazones (compounds 5, 5a–5g). However, compound activity across multiple assays varies and it is challenging to elucidate the favorable physicochemical characteristics of the studied compounds and guide further lead optimization. The aim of the current study is to apply exploratory data analysis in order to profile the biological effects of the novel hydrazide-hydrazones, gain insights related to their mechanisms of action in the context of in silico predictions and identify key predictor–outcome relationships. We collected a dataset from available in vitro studies of compounds 5, 5a–5g. It included cytotoxicity values, protection against hydrogen peroxide-induced damage in HepG2 and SH-SY5Y cells, two radical scavenging assays and a hemolysis assay across a range of treatment concentrations. SwissADME-based predictions of chemometric and ADME parameters and pro-oxidant enzyme docking data were generated to provide context for the interpretation of in vitro outcome patterns and identify causal relationships. Multiple factor analysis (MFA), followed by hierarchical clustering on principal components (HCPC), was applied to profile compounds’ biological behavior. This revealed that differences in the number of H-bond donors, in the permeability coefficient and in the docking scores to two pro-oxidant enzymes could aid in explaining the effects of compounds with similar in vitro profiles. HCPC differentiated 5a as mostly neuroprotective, 5 and 5d as hepatoprotective radical scavengers, 5g with higher docking affinity to 5-lipoxygenase (5-LOX) and myeloperoxidase (MPO) and 5b, 5c and 5f as having less H-bond donors and variable in vitro activity. The consensus application of three variable selection approaches based on standard lasso regression, robust penalized regression and random forest confirmed the relationships between some in vitro outcomes and LogP, pan-assay interference (PAINS) alerts, 5-LOX allosteric site docking and H-bond donor numbers. The exploratory analysis of the combined in vitro and in silico dataset provides useful insights which could help explain the major drivers behind the experimental results. It can be informative in the design of new, improved members of the series of novel N-pyrrolyl hydrazide-hydrazones with better neuroprotective potential and less side effects. Full article

In this study, we synthesized a novel trimethoprim derivative, 4-(((2-amino-5-(3,4,5-trimethoxybenzyl) pyrimidine-4-yl)imino)methyl)benzene-1,3-diol (HD), by the reaction of trimethoprim with 2,4-dihydroxybenzaldehyde. We then prepared metal complexes of this derivative with Cu(II), Co(II), Ni(II), Ag(I), and Zn(II) and functionalized them with ZnO and Au nanoparticles. Their structures were confirmed through ¹H NMR, mass spectrometry, FTIR, conductivity, thermal analysis, magnetic susceptibility, X-ray diffraction, UV-Vis spectroscopy, and TEM, revealing octahedral geometries for all complexes. Surface features were investigated using density functional theory (DFT) analysis. Pharmacokinetic parameters and target enzymes for HD and its complexes were computed using the SwissADME web tool, with the BOILED-Egg model indicating that HD and its Cu complex should be passively permeable via the blood-brain barrier and highly absorbed by the gastrointestinal tract (GIT), unlike the Ni, Co, Ag, and Zn complexes, which are predicted to show low GIT absorption. Molecular docking studies with the Caspase-3 enzyme (PDB code: 3GJQ) using the AutoDock 4.2 software demonstrated binding energies of −7.66, −8.36, −9.05, −8.62, −6.90, and −7.81 kcal/mol for HD and the Cu, Co, Ni, Ag, and Zn complexes, respectively, compared to −6.54 and −4.63 kcal/mol for TMP and 5-FU (5-fluorouracil), indicating a potential superior anticancer potential of the novel compounds. The anticancer activities of these complexes were evaluated using the MTT assay. The IC₅₀ values for 5-FU, TMP, HD, Cu-HD, HD@ZnONPs, Cu-HD@ZnONPs, HD@AuNPs, and Cu-HD@AuNPs were found to be 32.53, 80.76, 114.7, 61.66, 77, 53.13, 55.06, and 50.81 µg/mL, respectively. Notably, all derivatives exhibited higher activity against the HepG-2 cancer cell line than TMP, except for HD, which showed similar effectiveness to TMP. Real-time PCR analysis revealed that the Au-HD@AuNPs and Cu-HD@AuNPs significantly increased caspase-3 inhibition by 4.35- and 4.5-fold and P53 expression by 3.05- and 3.41-fold, respectively, indicating enhanced pro-apoptotic gene expression and apoptosis induction in HepG2 cells. Our findings demonstrate that these novel derivatives possess significant anticancer properties, with some complexes showing superior activity compared to standard drugs such as 5-Fluorouracil (5-FU) and Trimethoprim (TMP). This study highlights the potential of these nanocomposites as promising candidates for cancer therapy. Full article