Search Results (17,821)

Isoflurane is a widely used volatile anesthetic with context-dependent effects on neuronal survival, particularly in neurodegenerative conditions. Increasing evidence suggests that brief, sublethal stress exposure can induce adaptive cellular responses through hormesis-based preconditioning mechanisms. In this study, we investigated whether isoflurane preconditioning enhances neuronal tolerance to amyloid-β (Aβ)-induced toxicity and explored the underlying redox-dependent molecular pathways. Using HT-22 murine hippocampal neuronal cells, we demonstrate that short-term exposure to low-dose isoflurane induces a delayed neuroprotective phenotype characterized by improved cell viability, reduced apoptotic signaling, and maintained mitochondrial membrane potential following Aβ challenge. Mechanistically, isoflurane preconditioning elicited a mild and transient increase in intracellular reactive oxygen species (ROS), which is critical for the activation of the PI3K/Akt signaling pathway. Pharmacological scavenging of reactive oxygen species abolished Akt phosphorylation and reduced the protective effects of preconditioning, supporting a hormetic signaling model rather than direct antioxidant action. Following Akt activation, isoflurane preconditioning promoted the inhibitory phosphorylation of glycogen synthase kinase-3β (GSK-3β), decreased Keap1 protein levels, and facilitated nuclear translocation and transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Consequently, the expression of Nrf2-regulated antioxidant genes, including heme oxygenase-1, NAD(P)H quinone dehydrogenase 1 (NQO1), superoxide dismutase 1 and 2 (SOD1/2), and catalase, was significantly upregulated. Collectively, these findings indicate that isoflurane preconditioning confers neuroprotection through hormesis-like mild oxidative signaling and coordinated activation of endogenous antioxidant defenses rather than via direct antioxidant scavenging. Full article

Microphysiological systems (MPS) that recapitulate human organ functions have gained attention as alternatives to animal experiments in drug discovery, regenerative medicine, and toxicity assessments. However, preserving MPS with adherent cells remains a significant challenge. In this study, we developed a supercooling preservation method that enables the low-temperature storage of human-derived adherent cells without freezing. Using human hepatic sinusoidal endothelial cells (TMNK-1), we optimized the preservation conditions by assessing the temperature, cooling and rewarming rates, and preservation solutions. Under optimized conditions (preservation at −4 °C, −0.028 °C/min cooling, and +1.0 °C/min rewarming), high cell viability and preserved morphology were maintained for up to 7 days. When these conditions were applied to both two- and three-dimensional MPS containing TMNK-1 or HepG2 cells, post-preservation viability remained high, and no cell death or cytoskeletal disruption was observed. This supercooling preservation method has the potential to serve as a practical strategy for the temporary storage of MPS. Full article

Recent advances in enone chemistry have enabled the development of structurally optimized derivatives with improved anticancer selectivity. In this study, the cytotoxic activity and underlying mechanisms of sodium salts of four α,β-unsaturated enones (ES1–ES4), synthesized from vanillin-based scaffolds, were evaluated in human colorectal carcinoma (HCT-116), cervical adenocarcinoma (HeLa), and normal lung fibroblast (MRC-5) cell lines. All compounds exhibited concentration- and time-dependent cytotoxicity, with ES2 showing the highest potency (IC₅₀ = 14.25 μM in HCT-116 and 18.12 μM in HeLa at 72 h) and minimal toxicity toward MRC-5 cells (IC₅₀ > 90 μM). Although cisplatin demonstrated greater overall cytotoxicity, the enone salts displayed significantly higher selectivity indices, indicating a more favorable therapeutic window. Phase-contrast microscopy revealed characteristic morphological features of apoptosis, including cell rounding and membrane blebbing. Mechanistic investigations confirmed mitochondrial-mediated apoptosis, evidenced by increased early and late apoptotic populations, Bax upregulation, Bcl-2 downregulation, and caspase-3 activation. JC-10 staining demonstrated mitochondrial membrane depolarization accompanied by cytochrome c release. In addition, cell cycle analysis revealed pronounced G2/M phase arrest, particularly in HCT-116 cells. Collectively, these findings indicate that vanillin-derived enone sodium salts exert selective anticancer effects through mitochondrial apoptosis and cell cycle disruption, supporting their potential as low-toxicity anticancer candidates. Full article

HIV latency, driven by a complex interplay of host factors, remains a key barrier to viral clearance. Current latency-reversing agents (LRAs) demonstrate limited efficacy and specificity, and none have been approved for clinical use. Although natural products have shown promise as LRAs, the therapeutic potential of fungal metabolites remains underexplored. Candida albicans, a prevalent human commensal and opportunistic pathogen, produces diverse secondary metabolites that can influence host pathways, affecting latency dynamics. This study aimed to investigate the latency-modulating potential of secondary metabolites of C. albicans using an integrative network pharmacology and computational pipeline. C. albicans secondary metabolites were retrieved from the literature, screened for drug-likeness, and mapped to human targets and biological pathways annotated in HIV latency. Key metabolites, hub genes, and pathways were systematically characterized through network and computational analyses. Six drug-like candidates, identified from 185 absorption, distribution, metabolism, excretion, and toxicity (ADMET)-screened metabolites, collectively mapped to 369 human genes with a 6.5% overlap in HIV latency (176 shared and 20 hub genes). These overlapping genes were significantly enriched for signal transduction, membrane localization, and adaptive responses to chemical stimuli. Kyoto encyclopedia of genes and genomes (KEGG) enrichment revealed oncogenic diseases (non-small cell lung, pancreatic, and prostate cancers) and latency-associated cascades, including PD-L1/PD-1, HIF-1, Ras, PI3K-Akt, calcium, and cAMP signaling. Six hub targets (MAPK1, PIK3CA, MAPK3, EGFR, MTOR, and AKT1) were consistently annotated within the top 30 KEGG pathways and displayed strong binding affinities for MET 15 and MET 119. Molecular dynamics (MD) simulations confirmed favorable binding free energies (BFEs) and stable conformational dynamics for the top-ranked metabolite MET 15. C. albicans secondary metabolites preferentially target oncogenic signaling networks central to HIV latency maintenance, notably PI3K/AKT/MTOR and MAPK/ERK, which regulate cell survival, metabolic homeostasis, and viral transcriptional repression. MET 15 is a top-ranked candidate metabolite for HIV latency-reversing therapeutics and warrants experimental validation in established latency models. Full article

Chimeric antigen receptor T (CAR-T) cell therapy has become a standard of care for many hematological malignancies, and has significantly transformed treatment outcomes. However, CAR-T therapy is associated with specific toxicities, including infections. Although the anti-CD19 CAR-T risks are well-characterized, infectious complications following B-cell maturation antigen (BCMA)-directed CAR-T in multiple myeloma (MM) remain under-researched. In this study, we evaluated the incidence and clinical impact of cytomegalovirus (CMV), Epstein–Barr virus (EBV), and adenovirus (ADV) reactivations in 75 patients receiving anti-BCMA CAR-T for MM, and compared them to 60 patients receiving commercial anti-CD19 CAR-T for B-cell lymphoma (BCL). The viral reactivation rates were 20% for CMV and 8% for EBV in the MM group, vs. 31.7% and 3%, respectively, in the BCL group. No ADV reactivations were seen in either cohort. Most of the CMV reactivations (87% in the MM cohort and 68.5% in the BCL cohort) were asymptomatic and clinically insignificant, and had no impact on progression-free survival (PFS) or overall mortality. Overall, these findings suggest that although CMV and EBV reactivations are relatively common after anti-BCMA CAR-T, they are rarely associated with meaningful disease, and the risks do not exceed those of CD19-directed therapy. Thus, routine pre-emptive screening for these viruses may be unwarranted in asymptomatic patients. Full article

Objective: The aim of this case series was to investigate the safety and efficacy of vancomycin–gentamicin embedded PMMA beads (VGPB) in the setting of acute pyogenic soft tissue infections (STIs) of the extremities. Materials and Methods: A retrospective study of 19 cases diagnosed with pyogenic STIs of the lower or upper extremity in two academic institutions was conducted between January 2017 and December 2023. All patients underwent surgical debridement, systemic antibiotics and intrawound deposition of vancomycin and gentamicin embedded cement beads (2 g of vancomycin plus 1 g of gentamicin diluted in 40 g of PMMA). Upon second look (4th–7th day post-index surgery) the cement beads were removed, serum samples from the surgical site of infection and from peripheral blood were obtained and the concentration of eluted vancomycin and gentamicin was measured. Furthermore, the white blood cell count (WBC), C reactive protein serum levels (CRP) and erythrocyte sedimentation rate (ESR) were measured before the surgical debridement and after the end of the bead therapy. All patients were reevaluated after discharge with a mean follow-up of 4.4 years (range, 1 to 7.6). Results: Wound vancomycin and gentamicin levels were significantly higher than those measured in the serum (34.01 ± 4.47 μg/mL versus 11.96 ± 2.79 μg/mL, p < 0.001 and 5.75 ± 1.22 μg/mL versus 0.51 ± 0.14 μg/mL, p < 0.001 respectively). Serum vancomycin and gentamicin concentrations were below the level of toxicity and no adverse events related to antibiotic-embedded bead treatment were documented. Serum WBC, ESR and CRP levels before debridement (13,446 ± 935.7 c/μL, 42.3 ± 18.7 mm/h and 113.9 ± 20.26 mg/L respectively) were significantly higher than those after the end of treatment (7889 ± 1203.6 c/μL, p < 0.001; 30.3 ± 9.14 mm/h, p = 0.017; and 22.7 ± 6.68 mg/L, p < 0.001 respectively). Two cases (10.5%) had a local recurrence of their STIs. Both of them relapsed within 4 months after their treatment and both had Gram-negative pathogens. Conclusions: Vancomycin–gentamicin PMMA bead pouch therapy appears to be a safe and effective adjuvant treatment for pyogenic soft tissue infections, offering high local antibiotic availability without systemic adverse effects. Full article

Background: Photodynamic therapy (PDT) offers a promising complementary strategy for treating glioblastoma multiforme (GBM); however, limited control over photosensitizer activation and reduced efficacy under hypoxic conditions remain significant limitations. Methods: In this study, we present the synthesis and functional evaluation of Gal-SiX, an enzymatically activatable Si-xanthene-based activatable PDT agent designed to address these challenges. Prepared via an improved 10-step synthetic route, Gal-SiX exhibits clear turn-on fluorescence and absorbance responses upon β-galactosidase activation and efficiently generates reactive oxygen species in aqueous media. Results: Mechanistic studies revealed that Gal-SiX enables both Type I and Type II PDT pathways, a favorable feature for GBM environments characterized by restricted oxygen availability. In vitro assays conducted on U87MG glioblastoma cells and L929 healthy fibroblasts demonstrated light-dependent cytotoxicity, with IC₅₀ values of 3.30 μM and 7.19 μM, respectively. Gal-SiX also showed minimal dark toxicity (>80 μM) and potent light-induced cytotoxicity, yielding a phototoxicity index of 24.8 in glioblastoma cells. Confocal imaging and MTT assays consistently confirmed enzymatic activation and effective PDT response at the cellular level. Conclusions: Overall, this work introduces the first activatable Si-xanthene-based PDT agent for glioblastoma and provides the first evidence that the Si-xanthene scaffold can support dual Type I/II phototoxicity. These results underscore Gal-SiX’s potential as a PDT platform for addressing the unique constraints of GBM biology. Full article

Small-molecule immunomodulators have become important components of modern immunotherapy by targeting immune checkpoints, cytokine signaling pathways, metabolic enzymes, and intracellular kinases. Despite pharmacological rationale, many of these agents underperform clinically due to unfavorable physicochemical properties, rapid systemic clearance, limited target accumulation, and dose-limiting toxicities, reflecting inadequate exposure control rather than a lack of target validity. Polymeric micelles, formed through the self-assembly of amphiphilic block copolymers, offer a versatile delivery platform to address these challenges by enhancing solubility, modulating pharmacokinetics, enabling stimuli-responsive release, and facilitating targeted or synchronized co-delivery. In this review, we classify representative small-molecule immunomodulators according to their immunological targets and examine the delivery constraints that shape their therapeutic performance. We then discuss design principles of polymeric micelle systems, including solubilization-driven formulations, microenvironment-responsive architectures, spatial targeting strategies, and co-delivery approaches that align cytotoxic and immunomodulatory mechanisms. Attention is given to the distinction between direct immunomodulators and cytotoxic agents that induce immunogenic cell death, highlighting how micelle-based delivery can enhance efficacy through improved exposure control. By integrating immunopharmacology with formulation science, this review outlines how polymeric micelles may advance the efficacy and safety of small-molecule immunomodulators and identifies key considerations for future translational development. Full article

Silver nanoparticles synthesized using natural polysaccharides have received attention for their biocompatibility and potential selective anticancer activity. In this study, the physicochemical properties and biological activity of silver nanoparticles prepared using gums from Acacia senegal (ASS) and Acacia seyal (ASY) were compared. The gums were analyzed to determine their physicochemical characteristics and used as natural reducing and stabilizing agents in nanoparticle synthesis. The resulting nanoparticles were characterized using UV–visible spectroscopy, FTIR, dynamic light scattering, and zeta potential analysis. Their cytotoxicity was evaluated in MCF-7 breast cancer cells and HEK-293 normal cells using MTT assay, flow cytometry, and intracellular reactive oxygen species (ROS) measurement. Both gums showed properties consistent with Gum Arabic, with a higher protein content in ASS. ASS-derived nanoparticles were smaller and had greater colloidal stability. Both formulations reduced MCF-7 cell viability in a dose-dependent manner, with lower IC₅₀ values observed for the ASS-based nanoparticles. Apoptosis induction was associated with increased ROS generation. Limited cytotoxicity toward HEK-293 cells resulted in favorable selectivity indices. Acacia gum–mediated silver nanoparticles demonstrate selective anticancer activity, and gum composition significantly influences nanoparticle stability and bioactivity, supporting their potential application in breast cancer nanotherapy. Full article

Background: Cancer has emerged as the primary cause of death worldwide in recent years. Current cancer treatment strategies require improvement, creating a pressing need for the development of novel therapeutic agents. This study investigated the anticancer effects of a series of newly synthesized tri- and difluoromethylated spiro[5.5]trienone compounds and evaluated the antitumor efficacy of a lead compound, 3s. Methods: The methyl thiazolyl tetrazolium (MTT) assay was used to assess the effect of the trienone compounds on the growth of cancer cells. Cell cycle distribution and intracellular reactive oxygen species (ROS) levels were analyzed by flow cytometry. Protein expression was examined by Western blot. A mouse xenograft model was utilized to test the anticancer effects and toxicity of 3s in vivo. Results: All 21 tri- and difluoromethylated spiro[5.5]trienones exhibited inhibitory effects on the growth of cancer cells. Among them, compound 3s showed the strongest inhibitory effect. It induced cell cycle arrest at the G2/M phase and promoted apoptosis. Mechanistically, 3s activated JNK and ERK signaling and elevated intracellular ROS levels. Furthermore, in a mouse xenograft model, 3s significantly inhibited tumor growth with minimal toxicity. Conclusions: Compound 3s exhibits potent anticancer efficacy both in vitro and in vivo. The discovery of 3s offers new potential for cancer therapy. Full article

Anticancer peptides (ACPs) offer a promising alternative to conventional chemotherapy but face challenges, including poor selectivity, limited tumor penetration, low cellular uptake, and rapid degradation in serum. To address these barriers, we developed synthetic mRNAs encoding chimeric ACPs designed for enhanced intracellular delivery and activity. mRNAs for constructs SAK6L9AS(1X), SAK6L9AS(4X), and WTAS-K6L9(4X) were transcribed in vitro and tested against 4T1 breast cancer cells. Cytotoxicity was assessed by cell confluence and MTT assays, while apoptosis was evaluated using caspase 3/7 activation, PI staining, and Annexin V flow cytometry. Our results demonstrate that all SAK6L9AS variants induced robust apoptosis and cellular toxicity in 4T1 cells. Importantly, this work provides the first demonstration of intracellular expression of an mRNA-encoded ACP fused to a cell-penetrating peptide, thereby validating a modular platform for RNA-based delivery of anticancer agents. This study highlights the feasibility of mRNA-encoded peptide therapeutics as a scalable and customizable strategy for cancer treatment. By combining the advantages of mRNA delivery with rational peptide design, ACP chimeras can be expressed directly inside tumor cells, overcoming the limitations of exogenous peptide administration. Our findings support further development of synthetic mRNA therapeutics to generate potent, selective anticancer peptides with reduced systemic toxicity and improved translational potential. Full article

Background/Objectives: Doxorubicin is an anthracycline chemotherapeutic agent widely used in the treatment of breast cancer. However, its clinical utility is limited by the drug’s resistance development, low oral bioavailability, and dose-dependent side effects. The semi-essential amino acid, L-arginine, has gained attention as a potential adjuvant that could improve the drug distribution and cytotoxic effectiveness of chemotherapeutics. This study aimed to explore the multifunctional effect of L-arginine on the intestinal absorption and anti-breast cancer activity of doxorubicin. Methods: The rabbit in situ intestinal perfusion technique was employed to investigate the membrane transport parameters of doxorubicin both in the absence and presence of L-arginine. Furthermore, the effect of L-arginine on the cytotoxic activity of doxorubicin against breast cancer cells (MCF-7) was assessed using the MTT assay. Results: Co-perfusion of L-arginine with doxorubicin enhanced the fraction of doxorubicin absorbed, with a recorded 4.3-fold enhancement in the jejuno-ileum and a 1.5-fold enhancement in the colon segment. In MCF-7 cells, co-treatment with L-arginine resulted in a significant potentiation of doxorubicin cytotoxicity. At L-arginine concentrations of 10 μM and 50 μM, the recorded IC₅₀ decreased from 41.3 μM to 8.2 μM and to 22.1 μM, respectively. The superior efficacy of 10 μM L-arginine compared to 50 μM reflected a biphasic concentration-dependent response. Conclusions: L-arginine modulated two critical aspects of doxorubicin efficacy, intestinal absorption and cytotoxic activity. The biphasic response emphasizes the importance of L-arginine dose optimization. These findings support the potential of L-arginine as a safe adjuvant for developing oral doxorubicin formulations. This approach can reduce the dose-related toxicity of doxorubicin and improve therapeutic outcomes. Full article

Background/Objectives: Retinoblastoma represents the most common intraocular malignancy in childhood; however, the clinical applicability of mitomycin C (MMC) is restricted by dose-dependent ocular toxicity. Consequently, the development of pharmacological strategies that sensitize tumor cells to MMC while allowing dose reduction remains an unmet therapeutic objective. In this context, quercetin, a bioactive flavonoid with pleiotropic anticancer properties, has emerged as a potential chemosensitizing agent. Methods: Human retinoblastoma cell lines Y79 and WERI-Rb1 were exposed to MMC and quercetin, administered either individually or in fixed-ratio combinations. Cytotoxic responses were quantified through dose–response modeling and IC₅₀ determination following 24 and 48 h of treatment. Drug–drug interactions were quantitatively characterized using the Chou–Talalay combination index (CI) approach and isobologram analysis. Cell cycle distribution was assessed by propidium iodide (PI)-based flow cytometric analysis to evaluate treatment-associated alterations in cell cycle progression. Apoptotic cell death was assessed by Annexin V-FITC/PI flow cytometry, while transcriptional modulation of genes associated with apoptosis, cell cycle regulation, and oxidative stress (BAX, BCL-2, TP53, CASP3, CDKN1A, and HMOX1) was evaluated by qRT-PCR. Modulation of tumor-supportive signaling was examined by measuring VEGF and IL-6 secretion. Translational relevance was further investigated using a three-dimensional (3D) tumor spheroid model, and the functional contribution of reactive oxygen species (ROS) was interrogated through N-acetyl-L-cysteine (NAC) rescue experiments. Results: Quercetin significantly enhanced the cytotoxic activity of MMC in both retinoblastoma cell lines, with CI values below 1 across IC₅₀–IC₉₀ effect levels, indicating a synergistic pharmacological interaction. PI–FACS analysis revealed that combined MMC and quercetin treatment induced a pronounced accumulation of cells in the G2/M phase, consistent with cell cycle arrest, with a more marked effect observed in Y79 cells compared with WERI-Rb1 cells. Combination treatment resulted in a pronounced increase in apoptotic cell populations compared with single-agent exposure and triggered a coordinated pro-apoptotic transcriptional response, characterized by increased expression of BAX, TP53, CASP3, CDKN1A, and HMOX1, alongside suppression of BCL-2 and a marked shift in the BAX/BCL-2 ratio. Concurrently, VEGF and IL-6 secretion were significantly reduced, reflecting attenuation of pro-angiogenic and pro-inflammatory signaling. Notably, synergistic cytotoxicity was maintained in 3D tumor spheroids, where combined treatment induced spheroid shrinkage, architectural disruption, and reduced viability. NAC pretreatment diminished ROS accumulation and partially restored cell viability, indicating that oxidative stress contributes to, but does not solely account for, the observed synergistic cytotoxic effect. Conclusions: Collectively, these findings indicate that quercetin appears to function as an effective chemosensitizing adjuvant to MMC in retinoblastoma models, through transcriptional changes consistent with p53-associated apoptotic signaling at the transcriptional level, G2/M cell cycle arrest, and partial involvement of ROS-related cellular stress responses, along with suppression of tumor-supportive signaling pathways. The preservation of synergistic activity in 3D tumor spheroids supports the potential preclinical relevance of this combination. However, these findings are based on transcriptional and phenotypic analyses and should be interpreted as hypothesis-generating, requiring further validation through protein-level and in vivo studies before translational application. Full article

Deoxynivalenol (DON), a Fusarium-derived mycotoxin widely found in grain-based feed, has become a major global environmental contaminant. Reproductive toxicity is one of its most important toxic effects, yet systematic investigations covering both male and female reproductive injury remain limited. This study aimed to establish a combined strategy of network toxicology, molecular docking, molecular dynamics simulation, and single-cell RNA sequencing to evaluate the reproductive toxicity of DON. AKT1, EGFR, PIK3CA, PIK3R1, and SRC were identified as key targets involved in DON-induced reproductive injury. For testicular injury, the prolactin, Ras, HIF-1, and AGE-RAGE signaling pathways were closely associated with DON toxicity. For ovarian injury, the PI3K-Akt, HIF-1, prolactin, insulin, and AGE-RAGE signaling pathways were strongly implicated. Molecular docking demonstrated favorable binding affinities between DON and the hub targets, while molecular dynamics simulation further confirmed the stability of the DON–PIK3CA complex. Single-cell RNA sequencing analysis revealed that these five hub genes were highly expressed in both testicular (SRA667709:SRS3065430) and ovarian (SRA638923:SRS2797100) tissues. These findings deepen current understanding of DON-induced reproductive toxicity, provide new insights into the effects of environmental toxins on reproductive health, and offer a theoretical basis for future studies integrating DON exposure with in vivo validation of core targets and signaling pathways. Full article

This study reports the synthesis, spectroscopic characterization, and biological evaluation of a novel moxifloxacin hydrazide derivative (MOX-H) and its metal complexes with Co(II), Ni(II), Cu(II), VO(IV), and Gd(III). The ligand was synthesized by hydrazinolysis of moxifloxacin hydrochloride, and the resulting hydrazide was subsequently complexed with the respective metal salts. The interaction between MOX-H and the metal ions yielded the corresponding complexes, formulated as [Co(H₂O)Cl(MOX-H)₂]Cl·2.5H₂O, [Ni(H₂O)Cl(MOX-H)₂]Cl.4.5H₂O, [VO(MOX-H)₂]SO₄.3.5H₂O, [Gd (H₂O)(MOX-H)₂(NO₃)₂]NO₃.2H₂O, and [Cu(MOX-H)₂(H₂O)Cl]Cl·xH₂O (where x = 2, 2.5, 0.5, for products synthesized via template, microwave-assisted, and hydrothermal methods, respectively). The synthesized analogues were characterized by elemental analysis (CHN), FT-IR, UV-visible, and ¹H NMR spectroscopy, and mass spectrometry, as well as thermogravimetric (TG/DTG) and magnetic measurements. FT-IR spectra confirmed coordination through the hydrazide carbonyl and amine groups, while UV–visible and magnetic data indicated predominantly octahedral geometries. The thermal behavior exhibited multistep decomposition with activation parameters supporting exothermic processes. When compared to the free ligand, the metal complexes showed increased antimicrobial activity against both Gram-positive and Gram-negative bacteria and fungus species, particularly for the Co(II) and Cu(II) complexes, which showed the largest inhibition zones. The Cu(II)–MOX-H complex exhibited the lowest MIC values (4.88–9.76 µg/mL) among all tested compounds, confirming its outstanding antibacterial potency and high sensitivity compared to the free ligand and standard drug. Cytotoxicity assays demonstrated selective anticancer activity, with the Cu(II)–MOX-H complex showing the highest potency (IC₅₀ ≈ 2.95 µM against MCF-7 and IC₅₀ ≈ 0.98 µM against HepG-2), while maintaining minimal toxicity toward normal cells. These findings were corroborated by molecular docking investigations, which showed that the MOX-H complexes had substantial binding affinities (−9 to −10 kcal/mol) toward DNA topoisomerase II, consistent with their observed biological effects. Full article