Search Results (2,206)

Background: Drug-resistant epilepsy (DRE) affects approximately one-third of individuals with epilepsy, where seizures remain uncontrolled despite appropriate trials of at least two antiseizure medications (ASMs). Neuroinflammation, specifically chronic microglial activation, plays an important role in epileptogenesis, seizure perpetuation, and pharmacoresistance. Traditionally, antiseizure medications (ASMs) target neuronal excitability through modulation of ion channels and neurotransmitter systems; however, several ASMs, including sodium valproate and lamotrigine, have demonstrated anti-inflammatory and microglia-modulating properties beyond their conventional antiseizure mechanisms. Rational polytherapy involving combinations of ASMs with complementary mechanisms and anti-neuroinflammatory effects may provide enhanced seizure control while minimizing adverse effects. Among available combinations, sodium valproate and lamotrigine have consistently been regarded as one of the few combinations demonstrating potential pharmacodynamic synergism. Although several clinical studies have evaluated this combination in pediatric DRE, the overall evidence has not been quantitatively synthesized. Objectives: To systematically evaluate the efficacy and safety of rational polytherapy with sodium valproate plus lamotrigine in children with drug-resistant epilepsy. Methods: Electronic databases, including PubMed, Medline, Scopus, Embase, Web of Science, Google Scholar, PubMed Central, ScienceDirect, Cochrane Library, and clinicaltrials.gov, were systematically searched. Studies involving pediatric patients aged 18 years or less with DRE receiving polytherapy regimens containing sodium valproate plus lamotrigine were included. Primary outcomes were total treatment effect defined as ≥50% seizure reduction and seizure freedom. Secondary outcomes included changes in seizure frequency, adverse events, treatment discontinuation, and serious adverse events. Risk of bias was assessed using the Cochrane Risk of Bias tool and Newcastle–Ottawa Scale. Meta-analyses were performed using random-effects models. Results: A total of 7 studies met the eligibility criteria. The pooled proportion of patients achieving an overall treatment response was 65.3% (95% CI 51.8–78.8%), with high heterogeneity (I² = 63.4%, p = 0.027). Rational polytherapy with sodium valproate plus lamotrigine combination provided preliminary comparative evidence of higher responder rates in a single comparative trial, requiring confirmation in larger randomized trials. Overall, sodium valproate plus lamotrigine was well tolerated, and most reported adverse events were mild to moderate in severity. The pooled adverse event rate was 18.1% (95% CI 8.3–28.0%), with high heterogeneity (I² = 64.3%, p = 0.024). Conclusions: Rational polytherapy with sodium valproate plus lamotrigine that have both complementary antiseizure and immunomodulatory mechanisms appears to represent an effective and generally well-tolerated therapeutic strategy for pediatric drug-resistant epilepsy. However, the basis of this conclusion is derived mainly from observational studies, requiring confirmation in larger randomized trials. This systematic review provides quantitative evidence supporting its clinical use while highlighting the need for larger prospective comparative studies to strengthen the evidence base. Full article

Background: Breast cancer remains the most common malignant tumor among women worldwide. Although conventional treatments including surgery, chemotherapy, and radiotherapy are effective, they are confronted with challenges such as tumor heterogeneity, systemic toxicity, and recurrence driven by drug resistance. To overcome these limitations, natural products have emerged as promising therapeutic alternatives owing to their multi-target efficacy and favorable biocompatibility. However, their clinical translation is still hindered by poor chemical stability, low aqueous solubility, and inadequate bioavailability. Nanodelivery systems offer a transformative solution by enhancing bioavailability and enabling precision targeting through the enhanced permeation and retention effect, thereby widening the therapeutic window and minimizing off-target toxicity. Purpose: This review evaluates diverse nanoparticle-based delivery systems and their targeting mechanisms in natural product-based breast cancer therapy. By examining inherent advantages and translational challenges, this analysis provides critical insights into the clinical development and application of these nanoformulations. Methods: A systematic literature search was performed in PubMed, ScienceDirect, Springer, Taylor & Francis, and Web of Science to identify relevant studies on natural product-based nanoformulations for breast cancer therapy. Results: Natural products exert anti-breast cancer effects through mechanisms such as inducing apoptosis, arresting the cell cycle, inhibiting invasion and metastasis, suppressing angiogenesis, and regulating autophagy. To overcome clinical hurdles, three complementary targeting strategies have been developed: passive, active, and stimuli-responsive targeting. These advances are shifting nanomedicines toward active precision therapy, markedly improving the therapeutic index. With multiple formulations already approved or in clinical pipelines, this field is rapidly progressing from laboratory research to clinical implementation. Conclusions: Natural products possess potent anti-breast cancer effects, and the application of nanodelivery technology effectively overcomes their inherent limitations of poor stability and low bioavailability. Although preliminary findings are promising, large-scale, randomized controlled clinical trials are urgently needed to systematically evaluate their safety, efficacy, and practical potential for clinical translation in breast cancer management. Full article

Bispecific antibodies (bsAbs) and bispecific antibody–drug conjugates (bsADCs) represent promising classes of emerging targeted therapeutics with the potential to overcome tumor heterogeneity and resistance in colorectal cancer (CRC). BsAbs can simultaneously engage multiple tumor antigens or immune cells or bind two distinct epitopes within a single target, enabling mechanisms of action beyond the capabilities of monoclonal antibodies. Bispecific T cell engagers facilitate targeted destruction of tumors through immune cell recruitment, while dual immune checkpoint inhibitors enhance immune activation by blocking T cell inhibitory signals. Furthermore, bsAbs can mediate dual signaling pathway inhibition through binding multiple receptor tyrosine kinase receptors or other tumor cell surface proteins. BsADCs integrate the dual-antigen recognition of bsAbs with targeted payload delivery, utilizing receptor-mediated endocytosis to deliver potent cytotoxic payloads selectively to CRC cells, while minimizing systemic toxicity. Recent advances in bsAb engineering, linker chemistry, site-specific conjugation, and payload design have accelerated the development of bsADCs for solid tumors, including CRC. BsAbs and bsADCs provide opportunities to improve tumor selectivity, enhance internalization, overcome antigen escape, and expand the population of CRC patients eligible for targeted therapy. Emerging preclinical studies demonstrate encouraging anti-tumor activity for bispecific modalities in CRC, while early clinical trials are beginning to establish their translational potential. This review summarizes the current landscape of bsAbs and bsADCs in therapeutic development for CRC, highlighting key biological targets, engineering strategies, mechanisms of action, and clinical status. We also discuss the major challenges facing clinical translation and provide perspectives on future directions for bispecific therapies in CRC. Full article

MicroRNAs (miRNAs) are small non-coding RNAs that have emerged as critical regulators of gene expression and key cellular processes in cancer, including tumor cell proliferation, survival, metastasis, and both innate and adaptive immune responses within the tumor microenvironment. Through their ability to modulate immune cell development, differentiation, polarization, antigen presentation, cytokine signaling and immune checkpoint expression, miRNAs play a vital role in shaping immune responses and represent attractive therapeutic candidates for remodeling the tumor immune microenvironment. This review provides a comprehensive overview of the mechanisms through which miRNAs regulate anti-tumor immunity and contribute to immune evasion with particular emphasis on their role in modulating major immune checkpoint pathways, including PD-1/PD-L1, CTLA-4, LAG-3, TIM-3 and CD28-mediated signaling. We further examine the contribution of miRNAs to therapeutic resistance and discuss their potential integration with immune checkpoint blockade, chemotherapy, PARP inhibitors and targeted therapies to enhance antitumor efficacy and overcome treatment resistance. Recent advances in spatial transcriptomics and computational approaches have expanded our understanding of miRNA-mediated regulatory networks at single-cell and tissue levels and provide new insights into tumor–immune interactions. In addition, we evaluate the current progress in the clinical development of miRNA-based therapeutics, including miRNA mimics and inhibitors and discuss the major challenges associated with efficient delivery, off-target effects, immunogenicity and patient heterogeneity. Collectively, the evidence highlights the growing potential of miRNAs as diagnostic biomarkers, therapeutic targets and therapeutic tools in cancer immunotherapy. Continued advances in RNA therapeutics, delivery technologies and multi-omics approaches are expected to accelerate the clinical translation of miRNA-based strategies for personalized cancer therapy. Full article

Diabetes mellitus is a pervasive global health crisis, with type 2 diabetes (T2D) representing the majority of cases. While conventional pharmacological therapies exist, suboptimal efficacy, adverse effects, and inadequate glycemic control in a substantial proportion of patients highlight the need for complementary strategies. There is growing scientific and clinical interest in plant-based functional foods, including Ribes nigrum L. (blackcurrant), which is rich in bioactive phytochemicals such as anthocyanins, flavonols, and phenolic acids. This review evaluates the antidiabetic and metabolic regulatory potential of blackcurrant, focusing on its multi-target mechanisms of action. Available experimental evidence suggests that blackcurrants may influence glucose metabolism through several mechanisms, including inhibition of carbohydrate-digesting enzymes (α-amylase and α-glucosidase), modulation of intestinal glucose transporters (SGLT1 and GLUT2), and potential modulation of insulin sensitivity involving AMPK signaling and GLUT4 translocation. In addition, blackcurrant constituents may stimulate glucagon-like peptide-1 (GLP-1) secretion, modulate gut microbiota composition, and exert antioxidant and anti-inflammatory effects that counteract key drivers of insulin resistance and β-cell dysfunction. Supporting human studies indicate that blackcurrant consumption has been associated with attenuation of postprandial glycemic and insulinemic responses and modest improvements in cardiometabolic biomarkers, although findings remain limited by study size, duration, and formulation heterogeneity. Overall, Ribes nigrum represents a promising dietary adjunct for the prevention and management of T2D through multi-target metabolic regulation. Full article

Glioblastoma (GBM) is the most aggressive primary brain malignancy in adults, which remains difficult to treat because of extensive intratumoral heterogeneity, intrinsic and acquired treatment resistance, a profoundly immunosuppressive tumor microenvironment (TME), and restricted drug delivery across the blood–brain barrier (BBB). Owing to their relatively low molecular mass, potential for BBB penetration, and ability to modulate multiple targets, natural and synthetic compounds have attracted increasing interest as candidates for GBM treatment. This narrative review summarizes the mechanisms by which naturally derived compounds—including saponins, flavonoids, and sesquiterpene lactones—and synthetic small molecules exert anti-GBM effects on tumor and the TME. Their reported actions include suppressing key prosurvival pathways, such as the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR), nuclear factor kappa B (NF-κB), and mutant p53 signaling; activating regulated cell-death processes, including apoptosis, pyroptosis, and parthanatos, as well as autophagy-associated cell death; and remodeling the tumor immune milieu to promote CD8⁺ T-cell infiltration. In preclinical models, some of these agents also overcome temozolomide (TMZ) resistance and resensitize glioma stem cells (GSCs) to chemotherapy or radiotherapy. Future studies should prioritize molecularly informed patient stratification, rational combination strategies, and advanced nanocarrier-mediated delivery platforms to facilitate the clinical translation of small-molecule therapeutics for GBM. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and chronic low-grade inflammation. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), the systemic immune-inflammation index (SII), and the systemic inflammation response index (SIRI) are important markers used to evaluate inflammatory status in T2DM. This study aimed to compare inflammatory and metabolic parameters between patients receiving metformin monotherapy and those receiving metformin plus sodium-glucose cotransporter-2 (SGLT-2) inhibitor combination therapy in patients with newly diagnosed T2DM. Methods: This prospective observational study included 64 treatment-naïve patients with newly diagnosed T2DM. Patients were divided into two groups according to treatment strategy: metformin monotherapy (n = 32) and metformin plus SGLT-2 inhibitor combination therapy (n = 32). TNF-α, IL-6, SII, systemic inflammation response index (SIRI), neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP), metabolic parameters, and insulin resistance-related indices were evaluated at baseline and after six months. Baseline-adjusted multiple linear regression analyses were performed to assess between-group differences at six months, adjusting for the corresponding baseline biomarker value, baseline HbA1c, age, and sex. Results: After six months of follow-up, significant reductions in TNF-α, IL-6, glycated hemoglobin (HbA1c), and fasting plasma glucose levels were observed in both groups (p < 0.001). In baseline-adjusted analyses, the treatment-group association was not statistically significant for TNF-α (B = −26.80, β = −0.15, p = 0.213), CRP (B = 0.06, β = 0.00, p = 0.977), SII (B = −36.94, β = −0.11, p = 0.441), or NLR (B = −0.20, β = −0.18, p = 0.207). In contrast, the treatment group was associated with a lower six-month IL-6 level (B = −37.87, β = −0.31, p = 0.038; 95% CI, −73.52 to −2.23) after adjustment for baseline IL-6, baseline HbA1c, age, and sex. Serum uric acid levels were lower in the metformin plus SGLT-2 inhibitor group than in the metformin monotherapy group at six months in the unadjusted comparison (p = 0.016). However, the adjusted treatment-group association between treatment group and six-month serum uric acid levels was not statistically significant (B = −0.51, β = −0.20, p = 0.065). Conclusions: In patients with newly diagnosed T2DM, both treatment groups showed significant reductions in TNF-α and IL-6 levels over six months. After adjustment for baseline biomarker levels, baseline HbA1c, age, and sex, no significant incremental association with treatment group was detected for TNF-α, CRP, SII, or NLR, whereas a significant adjusted association was observed for IL-6. Given the observational design and physician-directed treatment allocation, the observed IL-6 association should not be interpreted as evidence of a causal anti-inflammatory effect of SGLT-2 inhibitor therapy. Full article

Rising drug resistance undermines current anti-influenza virus therapies. Although targeting the hemagglutinin (HA)–sialic acid receptor interaction is a promising strategy, progress is impeded by the lack of subtype-independent screening models. Herein, we established a fluorescence-based cell high-throughput model using fluorescein isothiocyanate-conjugated Sambucus Nigra Lectin (FITC-SNA) as a stable HA surrogate and α-2,6-sialyltransferase (ST6GAL1)-overexpressing MDCK cells to mimic the HA–receptor interface. This platform was designed to serve as an efficient primary screening tool to rapidly filter large compound libraries for potential binders to the receptor-binding interface. Screening 10,000 compounds identified Obatoclax Mesylate and Ethylparaben as primary hits. Both exhibited broad-spectrum HA inhibition activity, validating the model’s capability to identify compounds interfering with viral attachment. Further cellular antiviral assays revealed cytotoxicity for both compounds, resulting in low selectivity indexes (SIs), indicating that while these molecules effectively target the interaction site, they require substantial structural optimization for therapeutic use. Molecular docking confirmed their binding to type A H1N1, H3N2, and B/Victoria HA proteins, while ADMET predictions highlighted specific structural optimization needs to mitigate toxicity. In conclusion, this subtype-independent, highly specific high-throughput screening (HTS) model provides an efficient and reliable platform for early-stage influenza drug discovery and lead compound development. Full article

Polyendocrine metabolic ovarian syndrome (PMOS), renamed from polycystic ovary syndrome (PCOS) by global consensus in May 2026, is one of the most common endocrine diseases in women of reproductive age, affecting physical and mental health. Growing evidence suggests that medicine–food homology (MFH) plants and their bioactive compounds may help regulate PMOS-related metabolism and reproductive abnormalities through dietary intervention. This review summarizes their reported roles and potential mechanisms. Based on the existing literature, this review presents nine edible plant resources identified under the MFH/dietary-use framework and 21 bioactive constituents or constituent classes, all selected for detailed synthesis from a broader eligible evidence base and with reported PMOS-related bioactivity. Across preclinical studies, these constituents appear to act through convergent, multi-target mechanisms, including anti-inflammatory and antioxidant activities to reduce systemic inflammation, as well as restoring hormone balance, correcting abnormal lipid metabolism, relieving insulin resistance and protecting ovarian function. Importantly, the evidence base remains predominantly preclinical, with few human randomized trials. Key translational barriers include insufficient standardization of preparations and doses, limited oral bioavailability of several constituents, safety and herb–drug interaction concerns, and uncertain formulation feasibility for functional-food applications. By integrating evidence at the plant and compound levels, this review provides a mechanistic rationale—rather than clinical proof—for further investigation of dietary strategies relevant to PMOS and proposes a framework for the development and evaluation of MFH-based functional foods. Full article

Purpose: This review aims to provide an updated overview of Kirsten rat sarcoma viral oncogene homologue (KRAS) mutations in colorectal carcinoma (CRC), focusing on their role in tumorigenesis, prognostic implications, and recent advances in targeted therapy. Major findings: KRAS mutations occur in approximately 40% of colorectal cancers and play a central role in tumour initiation and progression through constitutive activation of MAPK pathways. Clinically, KRAS mutations are well established as predictors of resistance to anti-EGFR therapy. Increasing evidence also supports their role as prognostic biomarkers, with KRAS-mutant tumours associated with increased recurrence risk and reduced survival, including in patients undergoing hepatic metastasectomy. Therapeutically, recent advances, most notably KRAS G12C inhibitors and combination strategies targeting upstream or parallel pathways, have expanded treatment options, although efficacy varies across KRAS mutation subtypes. Conclusions: KRAS mutations have important implications for the behaviour, prognosis, and management of colorectal cancer. Integrating KRAS mutational status into clinical decision-making may enable more personalised prognostication and treatment strategies. Continued research is required to broaden effective targeted therapies for the diverse spectrum of KRAS-mutant disease. Full article

The formation of anti-permeability is a critical step in the in-situ repair of organic anti-corrosion coatings under seawater, yet it is significantly influenced by the surrounding marine environment, particularly seawater temperature and applied cathodic polarization potential. In this study, we systematically investigated the effects of temperature and cathodic polarization potential on the permeability of curing epoxy coatings in simulated shallow seawater. Our results demonstrate that the anti-permeability formation process is governed by the competition between seawater penetration and coating curing. At lower temperatures, the EIS-derived evolution of coating resistance suggested heterogeneous electrolyte uptake across the coating surface, whereas at elevated temperatures, the electrochemical response indicated a more uniform progression of ionic ingress. Moreover, enhanced cathodic polarization accelerated both seawater penetration and the curing reaction of the epoxy coating. The underlying mechanisms of temperature- and polarization-dependent permeability formation were discussed in detail, providing theoretical insights into the top-down permeation process during underwater curing, which may inform the development of more effective in situ repair strategies for organic coatings. Full article

Diabetes mellitus (DM) is a chronic metabolic disease which, if left untreated or poorly controlled, can lead to serious complications. This global public health challenge is frequently associated with a deficit of Mg, which is one of the most important elements in the human body and is indispensable for many metabolic processes and the maintenance of human health. Due to its antioxidant and anti-inflammatory properties, its mitochondrial-supportive function, and its crucial role in the secretion and action of insulin as well as metal ion homeostasis, Mg may have great potential in the treatment of diabetes and diabetic complications. Therefore, we collected studies on a possible association between Mg and diabetes in humans. In other words, we intended to summarize data on the efficacy of oral Mg supplementation on glycemic and insulinemic parameters and Mg levels in biological specimens from humans with DM, gestational diabetes (GDM), insulin resistance (IR), and prediabetes (Pre-D). Our work indicates that, in some cases, supplementation with Mg may improve glycemic and/or insulinemic indices in hypo- or normomagnesemic individuals suffering from diabetes or IR. However, the results of certain studies did not show any beneficial effects of Mg intervention. Therefore, based on the findings presented in the current review, it can be concluded that further long-term studies on a larger population are required to demonstrate the efficacy of oral Mg supplementation in hypo- or normomagnesemic subjects with diabetes or at risk of developing the disease. It also seems justified to introduce routine determination of blood Mg levels (especially the ionized Mg form) in patients with diabetes and in those at risk of IR and glucose metabolism disorders. Moreover, it remains to be clearly determined which patients could benefit most from supplementation with this mineral, as its deficiency may impair insulin sensitivity and glucose uptake. To sum up, the results reviewed in the present report do not definitively indicate that supplementation with Mg may be regarded as a public health strategy for improving the outcomes of diabetes despite the fact that, in some cases, Mg has been reported to have a positive effect on the metabolic profile in subjects with diabetes and may be used as an adjuvant therapy of this modern-age disease. Full article

Background: The dynamic advancement of pediatric hemato-oncology and intensified therapeutic protocols have significantly increased survival rates while simultaneously highlighting the challenge of long-term treatment complications. Within the cohort of adolescent and young adult (AYA) survivors, delayed neurocognitive deficits, often manifesting as the chemobrain phenotype, and psychosocial disorders constitute a particularly substantial burden. Contemporary neurogastroenterological evidence indicates a fundamental role of persistent dysbiosis and gut–brain axis dysfunction in the pathogenesis of these alterations. This review aims to critically synthesize translational evidence elucidating the impact of iatrogenic gut microbiota damage and modifiable dietary patterns on the development of long-term neurocognitive sequelae in survivors of early childhood cancer. Methods: A systematized narrative review was conducted in accordance with the SANRA guidelines by integrating data from in vivo models and observational studies. A comprehensive literature search across the PubMed, Embase, Cochrane Central, Scopus, and Web of Science databases up to June 2026 was performed utilizing the Population, Exposure, and Outcomes (PEO) framework. Results: Oncological therapies, including myeloablative conditioning and broad-spectrum antibiotic therapy, induce a microbial scar phenomenon characterized by the depletion of commensal Firmicutes in favor of resistant pathobionts. The subsequent decline in the synthesis of neuroprotective short-chain fatty acids (SCFAs) alongside the pathological activation of the kynurenine pathway disrupts central nervous system homeostasis. Translocation of lipopolysaccharides (LPSs) across the compromised intestinal barrier generates systemic inflammation recognized as inflammaging, which, in turn, stimulates neurotoxic microglial hyperreactivity. This pathophysiological cascade is accelerated by a pro-inflammatory Western diet, whereas anti-inflammatory interventions such as the MIND diet and postbiotics demonstrate measurable restorative potential. Conclusions: The pathophysiology of delayed neurotoxicity is largely a consequence of systemic neuroinflammation driven by intestinal dysbiosis. Implementing individualized dietary and microbiome-targeted strategies into survivorship care protocols constitutes a crucial direction for clinical prophylaxis. Validating their clinical efficacy in the AYA population necessitates prospective randomized controlled trials integrated with shotgun metagenomic sequencing. Full article

The global emergence of multidrug-resistant fungal pathogens, including Candida auris, Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, and Pneumocystis jirovecii, poses a growing threat to public health, particularly among immunocompromised individuals. The limited number of available antifungal drug classes and the rapid evolution of resistance mechanisms, including target-site mutations, efflux pump activation, biofilm formation, metabolic adaptation, and stress-response signaling, have substantially reduced treatment efficacy. This review provides a comprehensive overview of current antifungal therapies, their limitations, and emerging molecular targets for next-generation antifungal drug discovery. We highlight promising targets involved in fungal cell wall biosynthesis, membrane integrity, mitochondrial metabolism, virulence regulation, and host–pathogen interactions, emphasizing their interconnected roles within adaptive resistance networks. Attention is given to small-molecule isothiazolone-based inhibitors, including phosphoglucomutase-targeting compounds, as novel candidates capable of disrupting multiple fungal survival pathways. We further discuss advances in combination therapies, anti-virulence approaches, nanotechnology-based delivery systems, and artificial intelligence-driven drug discovery pipelines that integrate multi-omics data, structural modeling, molecular docking, and virtual screening to accelerate therapeutic development. These advances support a transition from conventional single-target strategies toward systems-level, precision-guided antifungal therapies, providing a framework for overcoming multidrug resistance and improving clinical outcomes in invasive fungal infections. Full article

Candida albicans biofilms are a major cause of persistent infections and contribute to antifungal resistance as well as limitations in drug delivery. Targeting virulence traits such as biofilm formation and hyphal transition represents an effective strategy for controlling fungal pathogenicity without exerting strong selective pressure on planktonic growth. In this study, a library of structurally diverse benzophenone derivatives was screened to identify compounds with antibiofilm and anti-hyphal activities against azole-resistant C. albicans. Most benzophenone derivatives exhibited weak antifungal activity (MIC ≥ 200 µg/mL). However, several halogenated benzophenones markedly suppressed biofilm formation. Among them, decafluorobenzophenone at 10 µg/mL displayed the strongest inhibition, reducing biofilm formation to approximately 1–2% of control levels while maintaining substantial planktonic cell viability. Microscopy confirmed hyphal suppression, while qRT-PCR showed a 36-fold reduction in ALS3 expression. These findings indicate that multi-halogenated benzophenones act primarily as anti-virulence agents targeting biofilm formation and hyphal development. Molecular docking suggested a possible interaction of decafluorobenzophenone with the Als3 binding pocket. Decafluorobenzophenone showed low toxicity, with unaffected Caenorhabditis elegans viability at 10 µg/mL, plant germination at 100 µg/mL, and only slight hemolysis at 100 µg/mL. The results highlight halogen substitution as a key structural determinant and identify benzophenone scaffolds as promising leads for developing novel antibiofilm strategies against azole-resistant Candida infections. Full article