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Results for “Molecular Docking Simulation”

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PubMed2026

Proteomic regulation of anti-proliferative and anti-migratory activity by potent phytochemicals from Pistacia integerrima J.L. Steward Ex Brandis via PI3K, AKT1, and KRAS for Lung Cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of mortality worldwide and remains a major therapeutic challenge due to high metastasis, drug resistance and limited treatments. Pistacia integerrima J.L. Steward Ex Brandis (PI) consists of flavonoids, steroids, terpenoids and phenolic compounds reported for pharmacological activities. The efficacy of potent bioactives from P. integerrima may be ascertained employing cytotoxic, antiproliferative, anti-migratory, and anti-metastatic evaluations in A549 NSCLC cells with proteomic profiling, molecular docking, and dynamics simulation study. METHODS AND RESULTS: PI EtAc produced significant dose-dependent cytotoxicity in A549 cells (100 µg/mL, p < 0.0001 in the MTT assay. There was a pronounced decrease in colony formation after treatment with EtAc, with 18.41% (p < 0.002), and markedly. Furthermore. PI EtAC markedly inhibited cell migration emphasized by wound healing and Transwell migration (p < 0.01) assays, indicating reduced metastatic migratory potential. Proteomic analysis demonstrated significant downregulation of Endoglin (CD105), KLK5 and MMP-2, indicating suppression of angiogenic and metastatic signalling pathways in the Human XL Oncology protein array. The interaction of major PI phytochemicals with key NSCLC-associated targets was recorded in Molecular docking, revealing favourable binding affinities of kaempferol, β- sitosterol, luteolin, and quercetin towards several oncogenic targets, including AKT1(- 7.6 kcal/mol), PI3K(- 9.4 kcal/mol), KRAS (- 8.5 kcal/mol) and MMP9 (- 8.1 kcal/mol). Molecular dynamics simulation confirmed the structural stability of the kaempferol -AKT1 complex throughout the 100 ns simulation. CONCLUSION: Pistacia integerrima bioactives exhibited significant anti-proliferative, anti-migratory, and anti-metastatic activities in vitro, which may provide scientific rationale identifying newer promising candidates for NSCLC.

Humans↗

PubMed1997

Inhibitors of urokinase reduce size of prostate cancer xenografts in severe combined immunodeficient mice.

Proteolytic enzymes are required to mediate tumor cell invasion and metastasis. The urokinase plasminogen activator (uPA) is commonly overexpressed by many human cancers. Therefore, uPA is a logical target to inhibit cancer invasion and metastasis. However, uPA inhibitors also reduce tumor growth. We used a mutated form of plasminogen activator inhibitor type 1 to conform a correlation between the inactivation of uPA and tumor size; we have compared these results with the action of p-aminobenzamidine and amiloride, known inhibitors of uPA. Our results show that blocking uPA by uPA inhibitors reduces tumor size in experimental animals. Our molecular simulation of docking inhibitors to the urokinase reveals that all tested small molecule inhibitors bind in proximity of uPA's specificity pocket, a critical site for future search of novel anticancer uPA inhibitors.

Amiloride↗

PubMedDate not supplied

Molecular determinants of the hanatoxin binding in voltage-gated K+-channel drk1.

The carboxyl terminus of S3 segment (S3(C)) in voltage-gated potassium channels was proposed to bear the binding site for gating modifier toxins like Hanatoxin and a helical secondary structural arrangement was suggested. Due to the lack of complete structure in high resolution for such a channel molecule, no further direct experimental data to elucidate the mechanism for their binding conformations could thus far be derived. In order to examine the putative three-dimensional structure of S3(C) and to illustrate the residues required for Hanatoxin binding, molecular simulation and docking were performed, based on the solution structure of Hanatoxin and the structural information from lysine-scanning results for S3(C) fragment. From our results, it is indicated that both hydrophobic and electrostatic interactions are utilized to stabilize the toxin binding. Detailed docking residues and appropriate orientation for binding regarding hydrophobic/-philic environments are also described. Compared with the functional data proposed by previous studies, the helical structural arrangement for the C-terminus of S3 segment in voltage-gated potassium channels can therefore be further emphasized.

Binding Sites↗

PubMed2025

Phytocompounds of Honey mesquite (Prosopis glandulosa) and Lodhra (Symplocos racemosa) in the management of COVID-19 associated rheumatoid arthritis (CARA).

COVID-19 persists globally with profound social and economic consequences, and its complex interplay with other diseases makes it a syndemic. Rheumatoid arthritis (RA), a chronic autoimmune disorder, has shown increased incidence during the pandemic, with patients displaying higher susceptibility to COVID-19. This overlap prompted the hypothesis of 'COVID-19-associated rheumatoid arthritis (CARA)'. The present study explores phytocompounds with anti-inflammatory and immunomodulatory properties as potential CARA therapeutics. Compounds from Prosopis glandulosa and Symplocos racemosa, both used in traditional medicine, were evaluated through molecular docking and simulation studies. Six inflammatory targets relevant to RA and COVID-19 -interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), human leukocyte antigen DR4 (HLA-DR4), signal transducer and activator of transcription 4 (STAT4), and peptidyl arginine deiminase 4 (PAD4) were selected. Among the tested ligands, salidroside showed the strongest binding affinity, with energies of - 8.20 kcal/mol (IL-6), - 7.67 kcal/mol (TNF-α), - 8.53 kcal/mol (GM-CSF), - 8.80 kcal/mol (HLA-DR4), - 8.18 kcal/mol (STAT4), and - 7.91 kcal/mol (PAD4), indicating stable interactions. These findings suggest salidroside could modulate key inflammatory pathways and potentially reduce cytokine storms in COVID-19 patients. Existing RA and COVID-19 treatments often cause immunosuppression, increasing vulnerability to opportunistic infections (Datta et al in J Biomol Struct Dyn 41(8):3281-3294, 2022). Immunomodulatory phytocompounds like salidroside may offer safer, targeted alternatives without compromising immune defenses. However, this study is based on in silico analyses, and warrants in vitro and in vivo validation. Nevertheless, present work may represent an important step towards novel therapeutic strategies for COVID-19 Associated Rheumatoid Arthritis (CARA).

COVID-19↗

PubMed2002

Molecular simulation reveals structural determinants of the hanatoxin binding in Kv2.1 channels.

The carboxyl terminus of the S3 segment (S3C) in voltage-gated potassium channels was suggested to be the binding site of gating modifier toxins like hanatoxin. It has also been proposed to have a helical secondary structural arrangement. The currently available structures in high resolution for such channel molecules are restricted to regions illustrating the pore function. Therefore no further direct experimental data to elucidate the detailed mechanism for such toxin binding can be derived. In order to examine the putative three-dimensional structure of S3C and to analyze the residues required for hanatoxin binding, molecular simulation and docking were performed, based on the solution structure of hanatoxin and the structural information from mutational scanning data for the S3C fragment in Kv2.1. Our results indicate that hydrophobic and electrostatic interactions are both utilized to stabilize the toxin binding. Precise docking residues and the appropriate orientation for binding regarding amphipathic environments are also described. Compared with the functional data proposed by previous studies, the helical structural arrangement for the C-terminus of the S3 segment in voltage-gated potassium channels can therefore be further emphasized and analyzed. The possible location/orientation for toxin binding with respect to membrane distribution around the S3C segment is also discussed in this paper.

Binding Sites↗

PubMed2002

Structural influence of hanatoxin binding on the carboxyl terminus of S3 segment in voltage-gated K(+)-channel Kv2.1.

The voltage-sensing domains of voltage-gated potassium channels Kv2.1 (drk1) contain four transmembrane segments in each subunit, termed S1 to S4. While S4 is known as the voltage sensor, the carboxyl terminus of S3 (S3C) bears a gradually broader interest concerning the site for gating modifier toxins like hanatoxin and thus the secondary structure arrangement as well as its surrounding environment. To further examine the putative three-dimensional (3-D) structure of S3C and to illustrate the residues required for hanatoxin binding (which may, in turn, show the influence on the S4 in terms of changes in channel gating), molecular simulations and dockings were performed. These were based on the solution structure of hanatoxin and the structural information from lysine-scanning results for S3C fragment. Our data suggest that several basic and acidic residues of hanatoxin are electrostatically and stereochemically mapped onto their partner residues on S3C helix, whereas some aromatic or hydrophobic residues located on the same helical fragment interact with the hydrophobic patch of the toxin upon binding. Therefore, a slight distortion of the S3C helix, in a direction toward the N-terminus of S4, may exist. Such conformational change of S3C upon toxin binding is presented as a possible explanation for the observed shift in hanatoxin binding-induced gating.

Animals↗

PubMed2024

Adeno-Associated Virus Type 5 Infection via PDGFRα Is Associated With Interstitial Lung Disease in Systemic Sclerosis and Generates Composite Peptides and Epitopes Recognized by the Agonistic Immunoglobulins Present in Patients With Systemic Sclerosis.

OBJECTIVE: The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFRα is targeted by the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus-PDGFRα complex. METHODS: The binding of monomeric human PDGFRα to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFRα locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL) fluid. Immune responses to AAV5 and PDGFRα were evaluated by SPR using SSc monoclonal anti-PDGFRα antibodies and immunoaffinity-purified anti-PDGFRα antibodies from sera of patients with SSc. RESULTS: AAV5 was detected in the BAL fluid of 41 of 66 patients with SSc with interstitial lung disease (62.1%) and in 17 of 66 controls (25.75%) (P < 0.001). In SSc lungs, AAV5 localized in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and of PDGFRα was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFRα antibodies identified spatially contiguous epitopes derived from PDGFRα and AAV5 that interacted with SSc agonistic antibodies to PDGFRα. These peptides were also able to bind total IgG isolated from patients with SSc, not from healthy controls. CONCLUSION: These data link AVV5 with the immune reactivity to endogenous antigens in SSc and provide a novel element in the pathogenesis of SSc.

Humans↗

PubMed2006

Evidence for a strong selenium-aromatic interaction derived from crystallographic data and ab initio quantum chemical calculations.

Increasing attention is being paid to the role of selenium, both as an essential component required for the activity of many enzymes and in the context of selenium-based pharmaceutical agents. A wide range of therapeutics that include selenium are on the market and under development, such as antihypertensive, anticancerogenic, antiviral, and immunosuppressive agents. Computer-aided drug design (CADD) has proven to be an important tool for the development of new drugs. Many CADD techniques, including docking, molecular dynamics simulation, and other receptor-based approaches, require an accurate understanding of the nature of the intermolecular forces that act to stabilize protein-ligand complexes; moreover, a quantitative assessment of these interactions furthers our efforts to rationalize the drug design process. In this paper, we consider one class of interaction involving selenium, that between Se and aromatic rings. Prior work has shown that interactions between divalent sulfur and aromatic rings are observed much more frequently than would be expected on the basis of chance, both in protein structures and the crystal structures of organic compounds that include these moieties. Recent studies on the optimization of inhibitor-protein binding also suggest that sulfur-aromatic interactions are important in stabilizing these complexes and may be crucial focal point for CADD. Given that selenium and sulfur have similar chemistry, and that selenium is significantly more polarizable, we propose that Se-aromatic interactions may also play an important stabilizing role in the structure of folded proteins and in drug-protein complexes. We have tested this hypothesis against data from the Cambridge Crystallographic Database and ab initio quantum chemical calculations. We have found evidence that selenium does interact strongly with aromatic rings and may play a role analogous to sulfur in stabilizing protein folds. In addition, selenium should be considered along with sulfur in rational drug design strategies that seek to improve binding to target protein sites that include aromatic rings.

Crystallography, X-Ray↗

PubMed2026

Discovery of the Underlying Mechanism of Ginger Juice Processed Ziziphi Spinosae Semen for Its Sedative-Hypnotic Effect on Insomnia Mice via Regulation of HPA Axis and cAMP/PKA Signaling Pathway.

Based on Traditional Chinese Medicine (TCM) theory, the efficacy and mechanism of Ginger juice processed Ziziphi Spinosae Semen (GJPZSS) for treating insomnia, particularly stress-related types, were investigated to provide empirical evidence. An insomnia model was induced in mice by DL-4-chlorophenylalanine (PCPA) and chronic tail clamping. The sedative effect was evaluated by behavioral tests. Serum components from GJPZSS were analyzed by UHPLC-Q-TOF-MS/MS, and 64 potential targets were identified. The cAMP signaling pathway was enriched as the core pathway by Kyoto Encyclopedia of genes and genomes (KEGG) analysis and was validated by molecular docking. GJPZSS was demonstrated to prolong sleep time, reduce immobility time, increase 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) levels, decrease hypothalamic-pituitary-adrenal (HPA) axis levels, and suppress neuronal death. The reduction of the cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the brain was also significantly inhibited. It was concluded that the sleep-improving effect of GJPZSS was mediated through the regulation of the HPA axis and the cAMP/PKA/CREB/BDNF signaling pathway.

Animals↗

PubMed2026

Exploring the Mechanism of Zhigancao Decoction in the Treatment of Chronic Heart Failure via Modulation of Oxidative Stress.

BACKGROUND: Zhigancao decoction has shown therapeutic potential in the management of chronic heart failure (CHF); however, the molecular mechanisms underlying its pharmacological effects remain incompletely understood. This study aimed to investigate its potential mechanisms, with a particular focus on oxidative stress-related pathways. METHODS: The chemical profile of Zhigancao decoction was characterized by LC-MS/MS, and putative targets were predicted using SwissTargetPrediction. A protein-protein interaction (PPI) network was established using the STRING database and Cytoscape software, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Differentially expressed genes from two GEO datasets (GSE9128 and GSE84796) were integrated with reactive oxygen species (ROS)-related genes to identify candidate targets. Network pharmacology and molecular docking were subsequently performed to investigate compound-target interactions. RESULTS: A total of 66 chemical constituents and 818 putative targets were characterized and collected, respectively. Among these targets, MMP9 emerged as a central candidate associated with the therapeutic effects of Zhigancao decoction. GO and KEGG enrichment analyses demonstrated that the core targets were significantly enriched in oxidative stress-related pathways, inflammatory signaling cascades, and cell fate regulatory pathways. Computational deconvolution of bulk transcriptomic data suggested marked alterations in the estimated immune cell composition of the CHF microenvironment. Network pharmacology analysis further indicated that multiple chemical constituents of Zhigancao decoction converge on MMP9 and its associated pathways. Molecular docking analysis demonstrated favorable binding affinities between 10 representative compounds and MMP9, with binding energies below -7.0 kcal/mol. CONCLUSIONS: In silico predictions suggest that Zhigancao decoction may exert potential therapeutic effects against CHF through computationally predicted targeting of MMP9 and associated oxidative stress- and immune-related pathways. These computational findings provide a theoretical foundation for future experimental investigations into the mechanisms of Zhigancao decoction in CHF, though clinical application would require confirmation through rigorous in vivo and clinical studies.

Oxidative Stress↗

PubMed2001

The X-ray structure of Aspergillus aculeatus polygalacturonase and a modeled structure of the polygalacturonase-octagalacturonate complex.

Polygalacturonases hydrolyze the alpha-(1-4) glycosidic bonds of de-esterified pectate in the smooth region of the plant cell wall. Crystal structures of polygalacturonase from Aspergillus aculeatus were determined at pH 4.5 and 8.5 both to 2.0 A resolution. A. aculeatus polygalacturonase is a glycoprotein with one N and ten O-glycosylation sites and folds into a right-handed parallel beta-helix. The structures of the three independent molecules are essentially the same, showing no dependency on pH or crystal packing, and are very similar to that of Aspergillus niger polygalacturonase. However, the structures of the long T1 loop containing a catalytic tyrosine residue are significantly different in the two proteins. A three-dimensional model showing the substrate binding mode for a family 28 hydrolase was obtained by a combined approach of flexible docking, molecular dynamics simulations, and energy minimization. The octagalacturonate substrate was modeled as an unbent irregular helix with the -1 ring in a half-chair ((4)H(3)) form that approaches the transition state conformation. A comparative modeling of the three polygalacturonases with known structure shows that six subsites ranging from -4 to +2 are clearly defined but subsites -5 and +3 may or may not be shaped depending on the nearby amino acid residues. Both distal subsites are mostly exposed to the solvent region and have weak binding affinity even if they exist. The complex model provides a clear explanation for the functions, either in catalysis or in substrate binding, of all conserved amino acid residues in the polygalacturonase family of proteins. Modeling suggests that the role of the conserved Asn157 and Tyr270, which had previously been unidentified, may be in transition state stabilization. In A. niger polygalacturonase, the long T1 loop may have to undergo conformational change upon binding of the substrate to bring the tyrosine residue close to subsite -1.

Amino Acid Sequence↗

PubMed2026

Identification and expression validation of key genes of Xiaozhengtongluo formula in the treatment of diabetic nephropathy by Mendelian randomization.

Xiaozhengtongluo formula (XZTL) has a positive effect on the treatment of diabetic nephropathy (DN), but its mechanism is not fully understood. Therefore, it is important to explore the key genes of XZTL in the treatment of DN. Differentially expressed genes (DEGs) between DN and control obtained from GSE96804, drug target genes of XZTL, and disease target genes of DN obtained from public databases were intersected. Genes of intersection were defined as candidate genes. Next, Mendelian randomization (MR) analysis was used to ascertain the causal associations between candidate genes and DN. Afterwards, key genes were confirmed through receiver operating characteristic (ROC) curve analysis and expression validation. Subsequently, enrichment analysis, molecular regulatory network analysis, and molecular docking were conducted. Finally, experimental verification of the expression levels of key genes was performed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Altogether, 29 candidate genes were screened via MR analysis, identifying APOD, IGFBP3, and LPL as significantly associated with DN. IGFBP3 and APOD were risk factors, whereas LPL was protective. Consistent expression trends across training and validation datasets defined them as key genes. All three were co-enriched in 26 pathways, including oxidative phosphorylation. Regulatory networks showed MIR497HG/hsa-miR-19a-3p regulated IGFBP3, and NEAT1/hsa-miR-29a-3p regulated LPL; IGFBP3 and LPL were co-targeted by SP3 and SP1. Molecular docking revealed APOD-baicalein, LPL-oleic acid, and IGFBP3-quercetin binding, suggesting therapeutic potential. RT-qPCR confirmed aberrant expression of these genes in DN, which was normalized by XZTL intervention. In this study, three key genes (APOD, IGFBP3, and LPL) of XZTL in the treatment of DN were finally obtained, providing mechanistic clues for understanding XZTL's multi-target mechanism and providing experimentally tractable candidate targets for DN molecular subtyping, targeted therapeutic development, and precision medicine approaches in TCM.

Diabetic Nephropathies↗

PubMed2025

Identification and validation of prognostic genes associated with mitochondrial nuclear genes in gastric cancer.

Mitochondrial-related nuclear genes (MNGs) have shown great importance in cancer diagnosis and prognosis, but their role in gastric cancer (GC) remains unclear. GC-related transcriptome data from the gene expression omnibus and cancer genome atlas databases were analyzed to identify differentially expressed MNGs. A prognostic risk model was constructed through univariate Cox and least absolute shrinkage and selection operator regression, validated by Kaplan-Meier (K-M) survival curve and receiver operating characteristic curve. This was followed by immune infiltration analysis, independent prognostic analysis, functional enrichment analysis, drug sensitivity analysis, drug prediction, molecular docking and construction of regulatory networks. Three prognostic genes (ATP8A2, COX15 and TARS2) were identified. The expression of TARS2 and COX15 was positively correlated with CNV, while ATP8A2 was unaffected. The risk model and nomogram, integrating risk score and clinicopathological factors, exhibited excellent predictive performance. A significant correlation was observed between prognostic genes and differential immune cells, such as T cells, B cells, and NK cells. BMS-754807, Gefitinib, JQ1, Lapatinib, and Sapitinib exhibited significant differences in sensitivity between the high-risk group and the low-risk group. The results of molecular docking showed TP8A2 has stable binding ability with cytosine, COX15 with indomethacin, and TARS2 with bisacodyl. RT-qPCR revealed downregulation of ATP8A2 and upregulation of COX15 and TARS2 in GC samples. MNGs, including ATP8A2, COX15, and TARS2, demonstrated significant associations with immune infiltration, CNV, and prognostic outcomes of GC.

Humans↗

PubMed2026

Structure-based drug design of small-molecule c-Myc G-quadruplex binders.

The c-Myc oncogene is crucial in tumorigenesis. Although it is a promising therapeutic target, its protein lacks a conventional drug-binding pocket, making it traditionally "undruggable". Recent studies show that the c-Myc promoter can form a G-quadruplex (G4) structure, which suppresses transcription and offers a new strategy for indirect inhibition. In this study, structure-based virtual screening was performed using the c-Myc G4 crystal structure to screen the ChemDiv compound library, aiming to identify small molecules that bind to the G4 structure. Candidate compounds were evaluated in preliminary in vitro assays for biological activity. The results showed that Y502-3888 binds to the c-Myc G4 and downregulates c-Myc expression at both mRNA and protein levels. Collectively, these findings support the potential of Y502-3888 as a c-Myc G4 binder for the treatment of multiple myeloma (MM), providing a foundation for future development of anticancer agents targeting the c-Myc G4.

G-Quadruplexes↗

PubMed2026

Identification and validation of natural dengue virus NS1 inhibitors with promising antiviral potential.

Dengue infection remains a major global public health challenge, with no specific antiviral therapy currently available. The dengue virus non-structural protein 1 (NS1) exists in both intracellular and secreted forms playing a pivotal role in viral replication, immune evasion, and pathogenesis, particularly by contributing to endothelial disruption and vascular leakage during severe disease, thereby making it a promising therapeutic target. In silico screening identified berberine, betulinic acid, and ursolic acid as top candidates, exhibiting high binding affinities and stable interactions within the NS1 binding pocket. These computational predictions were further validated by biophysical assays, which demonstrated strong and specific binding interactions between the purified NS1 protein and the selected compounds. All three compounds significantly reduced viral genome levels, with the highest inhibition observed for berberine (60%), and followed by betulinic acid (40%) and ursolic acid (28%). Consistently, berberine showed the most potent inhibition of both intracellular and extracellular NS1. Overall, these findings highlight the inhibitory potential of natural compounds against DENV NS1 and provide a strong foundation for the development of NS1-targeted antivirals as a novel therapeutic strategy against dengue infection.

Antiviral Agents↗

PubMed2026

Whole-genome analysis of Brevibacterium sanguinis AZMABM HM27: a bacterial isolate from the sea anemone Radianthus magnifica and exhibiting promising multi-therapeutic properties.

BACKGROUND: The marine anemone Radianthus magnifica harbors symbiotic microbes with promising biomedical potential, yet their diversity and therapeutic properties remain underexplored. This study aimed to characterize a symbiotic bacterium isolated from R. magnifica collected from Samalona Island, Indonesia, and to evaluate its multi-therapeutic potential. METHODS: Strain AZMABM HM27 was characterized using whole-genome sequencing, functional annotation, biosynthetic gene cluster prediction, molecular docking, and in vitro bioactivity assays. RESULTS: Phylogenetic and genome-based analyses confirmed AZMABM HM27 as Brevibacterium sanguinis, with an OrthoANI value of 97.37% and a dDDH value of 76.50% against the type strain. The genome comprises a 3,834,082 bp chromosome encoding 3,362 protein-coding genes, including 95 genes involved in secondary metabolite biosynthesis. Five biosynthetic gene clusters were predicted, including those associated with ectoine, terpene, and siderophore production. The crude extract demonstrated antioxidant activity (IC₅₀ = 0.87 mg/mL), anti-inflammatory activity (up to 60% inhibition), antidiabetic activity through α-glucosidase inhibition (up to 40% inhibition), and dose-dependent antiproliferative activity against MCF-7 breast cancer cells (74.10% viability at 1 mg/mL). Molecular docking identified a lead compound, 8,9,9,10,10,11-hexafluoro-4,4-dimethyl-3,5-dioxatetracyclo [5.4.1.0(2,6)0.0(8,11)] dodecane, with strong binding affinities to selected therapeutic targets. CONCLUSIONS: B. sanguinis AZMABM HM27 represents a marine symbiotic strain associated with R. magnifica and a promising source of bioactive compounds with antioxidant, anti-inflammatory, antidiabetic, and antiproliferative potential. Further purification, structural elucidation, and in vivo studies are warranted to validate its therapeutic potential.

Animals↗

PubMed2026

Functional Characterization of a Novel Flavonoid O-methyltransferase From Polar Pedobacter sp. PAMC26386 and Bioactivity Assessment of Flavonoids.

Flavonoid O-methyltransferases (OMTs) catalyze the methylation of flavonoid hydroxyl groups, enhancing structural diversity and biological activity. In this study, we identified and characterized a novel Class I flavonoid OMT from the Antarctic bacterium Pedobacter sp. PAMC26386. Despite originating from a cold-adapted organism, the enzyme exhibited high catalytic activity at 55 °C and a strong preference for Co²⁺ as a cofactor. Sequence and phylogenetic analyses confirmed its classification as a flavonoid-specific OMT and revealed conserved motifs for S-adenosyl-L-methionine (SAM) binding and metal coordination. The enzyme accepted a wide range of flavonoid substrates, with quercetin and fisetin showing the highest activities. Kinetic analysis indicated greater substrate affinity for quercetin (Km = 36.55 µM) than for fisetin (Km = 49.41 µM). Whole-cell biotransformation using recombinant Escherichia coli C41 co-expressing the OMT and metK enabled efficient intracellular methylation, yielding 62.5 mg L⁻¹ of methylated quercetin and 55.5 mg L⁻¹ of 3'-O-methyl fisetin. The predicted methylation site at the 3'-hydroxyl of fisetin, determined by molecular docking, was confirmed by NMR spectroscopy. Notably, the previously reported 3'-O-methyl fisetin showed enhanced in vitro anticancer activity against mouse breast cancer cells and selectively improved antimycobacterial activity against Mycobacterium tuberculosis compared to the parent compound. To our knowledge, this study is among the first to report the enzymatic production of 3'-O-methyl fisetin using a polar microbial OMT that is optimally active at elevated temperatures in the presence of Co²⁺. The increased bioactivity compared to the parent compounds highlights the potential of this OMT as a biocatalyst for the sustainable production of pharmaceutically relevant methylated flavonoids.

Flavonoids↗

PubMed2026

Multi-omics identification of therapeutic targets of compound sappan decoction in hepatocellular carcinoma.

BACKGROUND: Compound sappan decoction (CSD) is a multi-herbal traditional Chinese medicine formulation with clinical relevance in hepatocellular carcinoma (HCC). However, its therapeutic mechanisms remain unclear. METHODS: Bioactive compounds of CSD were identified and standardized using pharmacological and chemical databases. Potential targets were predicted via multiple target inference platforms. HCC-related genes were curated from comprehensive disease databases. Summary-data-based Mendelian randomization (SMR) was conducted to infer causal relationships between compound targets and HCC risk using large-scale quantitative trait loci (QTL) datasets and HCC genome-wide association study data. Colocalization analysis, protein-protein interaction (PPI) network construction, and GO/KEGG enrichment were performed on SMR-identified targets. Molecular docking evaluated binding affinities of representative compounds to prioritized targets. RESULTS: A total of 784 overlapping genes between predicted CSD targets and HCC-related genes were subjected to SMR analysis. Among these, 22 targets were significantly associated with HCC risk based on transcriptomic or proteomic QTLs and showed colocalization evidence. Notably, four targets (ADRB2, APOE, SYK, and PGF) were supported by both replication in an independent cohort and strong colocalization. These 22 targets were enriched in apoptosis, PI3K-Akt signaling, redox metabolism, and detoxification pathways. PPI analysis revealed central hubs including MMP9, BCL2, CASP1, and MCL1. Molecular docking demonstrated strong binding of APOE to quercetin, PGF to luteolin-7-olate, and SYK to kaempferol. CONCLUSIONS: CSD may exert therapeutic effects on HCC through modulation of genetically validated targets involved in tumor progression, inflammation, and metabolic reprogramming, supporting its potential clinical utility as an adjunctive treatment strategy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s12672-026-04740-8.

Caesalpinia↗