Journal of Biochemical and Molecular Toxicology最新文献

Plausible Action of N-(3,4-Dimethoxy-Phenyl)-6,7-Dimethoxyquinazoline-4-Amine (TKM01) as an Armor Against Alzheimer's Disease: In Silico and In Vivo Insights N-(3,4-二甲氧基苯基)-6,7-二甲氧基喹唑啉-4-胺（TKM01）作为阿尔茨海默病防护剂的合理作用：硅学和体内观察。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-18 DOI: 10.1002/jbt.70048

Mohd Kashif, Karthikeyan Chandrabose, Ashok Kumar Pandurangan

{"title":"Plausible Action of N-(3,4-Dimethoxy-Phenyl)-6,7-Dimethoxyquinazoline-4-Amine (TKM01) as an Armor Against Alzheimer's Disease: In Silico and In Vivo Insights","authors":"Mohd Kashif, Karthikeyan Chandrabose, Ashok Kumar Pandurangan","doi":"10.1002/jbt.70048","DOIUrl":"10.1002/jbt.70048","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) affects millions of people and has limited treatment options, thus making it a global health concern. Amyloid β (Aβ), a disrupted cholinergic system with high acetylcholinesterase (AChE), oxidative stress (OS), reduced antioxidants, and neuroinflammation are key factors influencing AD progression. Prior research has shown that AChE can interact with Aβ and increase its accumulation and neurotoxicity, so targeting AChEs and Aβ could be a potential therapeutic approach for AD treatment. It has been known that nonsteroidal anti-inflammatory drugs (NSAIDs) can inhibit Aβ accumulation. Previously, TKM01, a derivative of 4-anilinoquinazoline, has demonstrated inhibitory effects against GSK-3β—a regulator in AD progression. The current research included molecular docking studies of NSAIDs and TKM01 with Aβ and AChEs as targets. TKM01 exhibited a higher binding affinity with Aβ among all tested compounds. Molecular dynamic (MD) simulations confirmed the stability of the protein-TKM01 complexes. TKM01 also exhibited favorable drug-likeness properties, and no hepatoxicity was visualized in comparison with other compounds. Further, in vitro assay showed an inhibitory action of TKM01 (50–1200 µg/mL) on AChEs. In the in vivo studies on zebrafish larvae brains, we found that TKM01 (120 and 240 µg/mL) reduced the levels of AChEs and lipid peroxidation (LPO) and increased antioxidant superoxide dismutase (SOD) and catalase (CAT) in AlCl<sub>3</sub>(80 µM)-induced AD-like model. Additionally, TKM01 treatment was found to decrease pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. The current study demonstrates that TKM01 can be used to treat AD. Nonetheless, experimental validation is needed to reveal the cellular, sub-cellular, and molecular mechanisms and possible implications at a clinical stage.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Astaxanthin-S-Allyl Cysteine Ester Protects Pancreatic β-Cell From Glucolipotoxicity by Suppressing Oxidative Stress, Endoplasmic Reticulum Stress and mTOR Pathway Dysregulation 虾青素-S-烯丙基半胱氨酸酯通过抑制氧化应激、内质网应激和 mTOR 通路失调保护胰腺 β 细胞免受糖脂毒性影响

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-18 DOI: 10.1002/jbt.70058

Penislusshiyan Sakayanathan, Chitra Loganathan, Palvannan Thayumanavan

{"title":"Astaxanthin-S-Allyl Cysteine Ester Protects Pancreatic β-Cell From Glucolipotoxicity by Suppressing Oxidative Stress, Endoplasmic Reticulum Stress and mTOR Pathway Dysregulation","authors":"Penislusshiyan Sakayanathan, Chitra Loganathan, Palvannan Thayumanavan","doi":"10.1002/jbt.70058","DOIUrl":"10.1002/jbt.70058","url":null,"abstract":"<div>\u0000 \u0000 <p>Glucolipotoxicity (GLT) has emerged as established mechanism in the progression of diabetes. Identifying compounds that mitigate GLT-induced deleterious effect on β-cells are considered important strategy to overcome diabetes. Hence, in the present study, astaxanthin-s-allyl cysteine (AST-SAC) diester was studied against GLT in β-cells. <i>Mus musculus</i> pancreatic β-cell line (βTC-tet) was treated with high glucose (25 mM; HG) and 95 μM palmitate (PA) for 24 h to induce GLT. AST-SAC at various concentrations (5, 10, and 15 μg/ml) were treated to understand the protective effect against HG + PA exposure in β-cells. Under HG + PA exposure conditions oxidative stress, deregulation of mTOR pathway and endoplasmic reticulum (ER) stress are witnessed. AST-SAC treatment eased oxidative stress, mitochondrial depolarization, DNA damage, calcium overload and accumulation of autophagosome against HG + PA exposure conditions thereby protected the cell viability of β-cells. AST-SAC maintained the level of proteins involved in mTOR pathway under HG + PA exposure conditions. Also, AST-SAC treatment has mitigated the increased expression of genes and proteins such as IRE1 and PERK involved in ER stress-mediated unfolded protein response (UPR) signaling pathways. In correspondence to it, the expression of genes involved in insulin secretion was preserved by AST-SAC. Due to these protective effects of AST-SAC the insulin secretion was well-maintained in β-cells under HG + PA exposure conditions. AST-SAC through normalizing antioxidant status and mTOR axis as well as preventing the harmful effect of ER-stress mediated UPR pathway has promoted the β-cell survival and insulin secretion against GLT. Simultaneously targeting oxidative stress/mTOR axis/ER stress is required to efficiently overcome GLT in β-cells.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Paeonol Alleviates Subarachnoid Hemorrhage Injury in Rats Through Upregulation of SIRT1 and Inhibition of HMGB1/TLR4/MyD88/NF-κB Pathway 芍药酚通过上调 SIRT1 和抑制 HMGB1/TLR4/MyD88/NF-κB 通路缓解大鼠蛛网膜下腔出血损伤

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-18 DOI: 10.1002/jbt.70035

Zhao Liu, Jun Zhu, Enyu Pan, Lujun Pang, Xiwei Zhou, Yanjun Che

{"title":"Paeonol Alleviates Subarachnoid Hemorrhage Injury in Rats Through Upregulation of SIRT1 and Inhibition of HMGB1/TLR4/MyD88/NF-κB Pathway","authors":"Zhao Liu, Jun Zhu, Enyu Pan, Lujun Pang, Xiwei Zhou, Yanjun Che","doi":"10.1002/jbt.70035","DOIUrl":"10.1002/jbt.70035","url":null,"abstract":"<div>\u0000 \u0000 <p>Paeonol is a principle bioactive compound separated from the root bark of Cortex Moutan and has been shown to confer various biological functions, including antineuroinflammation and neuroprotection. Inflammation, blood–brain barrier (BBB), permeability, and apoptosis are three major underlying mechanisms involved in early brain injury (EBI) postsubarachnoid hemorrhage (SAH). This study aimed to detect the roles and mechanisms of paeonol in EBI following SAH. A SAH model was established by an endovascular perforation method in Sprague-Dawley rats. The localizations of HMGB1 and p65 were identified by immunofluorescence staining. Protein levels were measured by western blot analysis. The serum levels of HMGB1 and the levels of inflammatory cytokines in the brain cortex were evaluated by ELISA. Hematoxylin and eosin staining was conducted to detect neuronal degeneration. Brain water content and Evans blue extravasation were assessed to determine EBI. Neuronal apoptosis was examined by TUNEL. Paeonol deacetylated HMGB1 by upregulating SIRT1 level. SIRT1 inhibition attenuated the protective effects of paeonol against neurological dysfunctions, brain edema, and BBB disruption. SIRT1 inhibition rescued the paeonol-induced inhibition in inflammatory response. The paeonol-induced decrease in neuronal apoptosis was restored by SIRT1 inhibitor. The paeonol-mediated deactivated TLR4/MyD88/NF-κB pathway was activated by SIRT1 inhibitor. Paeonol alleviates the SAH injury in rats by upregulating SIRT1 to inactivate the HMGB1/TLR4/MyD88/NF-κB pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting CD36 With EP 80317 Reduces Remote Inflammatory Response to Hind Limb Ischemia-Reperfusion in Mice 用 EP 80317 靶向 CD36 可降低小鼠后肢缺血再灌注的远端炎症反应

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-18 DOI: 10.1002/jbt.70057

Hanan Elimam, Jade Gauvin, David N. Huynh, Liliane Ménard, Marie-Lynn Al-Hawat, Diala Harb, William D. Lubell, André C. Carpentier, Huy Ong, Sylvie Marleau

{"title":"Targeting CD36 With EP 80317 Reduces Remote Inflammatory Response to Hind Limb Ischemia-Reperfusion in Mice","authors":"Hanan Elimam, Jade Gauvin, David N. Huynh, Liliane Ménard, Marie-Lynn Al-Hawat, Diala Harb, William D. Lubell, André C. Carpentier, Huy Ong, Sylvie Marleau","doi":"10.1002/jbt.70057","DOIUrl":"10.1002/jbt.70057","url":null,"abstract":"<p>Reperfusion of ischemic skeletal muscle triggers oxidative stress and an immediate inflammatory reaction, leading to damage of distant organs such as the lungs. The inflammatory process implicates numerous mediators, including cytokines, chemokines, and arachidonic acid metabolites. In the orchestration of the inflammatory cascade, a critical role is played by the cluster of differentiation-36 receptor (CD36), a scavenger receptor class B protein (SR<i>-</i>B2) which is expressed on macrophages and functions as a Toll-like receptor coreceptor. A mouse model of hind limb ischemia-reperfusion has been used to investigate the interplay between CD36 signaling and remote inflammation: leukocyte recruitment, regulation of the nucleotide-binding domain leucin-rich repeat and pyrin-containing receptor 3 (NLRP3) inflammasome, and release of nuclear factor-kappa B (NF-ĸB) and arachidonic acid metabolites. Levels of reactive oxygen species, inflammatory mediators, and gene expression were measured in blood and lung tissue samples collected from anesthetized mice on which unilateral hind limb ischemia was induced by rubber band constriction for 30 min followed by reperfusion for 3 h. The CD36 modulator EP 80317, a member of the growth hormone releasing peptide 6 family, was employed as a pharmacological agent to mitigate distant lung injury following skeletal limb ischemia-reperfusion. Targeting CD36 on monocytes/macrophages, EP 80317 abated pro-inflammatory signaling and transcriptional activity encompassing lipid and cytokine mediators. Targeting CD36 was shown to offer promise for curtailing tissue injury following hind limb ischemia-reperfusion.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In Vitro and Vivo Experiments Revealing Astragalin Inhibited Lung Adenocarcinoma Development via LINC00582/miR-140-3P/PDPK1 体外和体内实验揭示黄芪通过 LINC00582/miR-140-3P/PDPK1 抑制肺腺癌发展

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-18 DOI: 10.1002/jbt.70042

Juncheng Bai, Yuxin Chen, Geyu Zhao, Rong Gui

{"title":"In Vitro and Vivo Experiments Revealing Astragalin Inhibited Lung Adenocarcinoma Development via LINC00582/miR-140-3P/PDPK1","authors":"Juncheng Bai, Yuxin Chen, Geyu Zhao, Rong Gui","doi":"10.1002/jbt.70042","DOIUrl":"10.1002/jbt.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>This study aimed to explore the mechanism of the development of lung adenocarcinoma (LUAD) treated by astragalin. Transcriptome sequencing was performed to obtain the gene profile of LUAD treated by astragalin. Combining with bioinformatics analysis including differential gene screening, function enrichment analysis (gene ontology and KEGG), and ceRNA construction, we obtained the novel mechanism of lncRNA mediated miRNA/mRNA axis. Then, the cell experiments were performed to examine the role of lncRNA in cell proliferation, migration and invasion, and apoptosis for LUAD treated with astragalin. Moreover, the tumor formation in nude mice was carried out to detect the ceRNA mechanism in LUAD treated by astragalin in vivo. The lncRNA mediated ceRNA network was obtained, that is, LINC00852 LINC00582/miR-140-3p/PDPK1 played an important role in LUAD treated by astragalin. Function experiments indicated that si-LINC00852 inhibited LUAD cell proliferation, migration and invasion, and promoted cell apoptosis via miR-140-3p/PDPK1 (<i>p</i> < 0.05, <i>p</i> < 0.01). The animal experiments further confirmed that si-LINC00852 inhibited tumor growth through miR-140-3p/PDPK1 in vivo. Conversely, this study provides comprehensive insights into the diagnostic and therapeutic implications of LINC00582 in LUAD, LINC00582 mediated miR-140-3p/PDPK1 axis was the novel drug target of astragalin for treating LUAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of the Oncogenic Role of the Circ_0001326/miR-577/VDAC1 Cascade in Prostate Cancer 确定 Circ_0001326/miR-577/VDAC1 级联在前列腺癌中的致癌作用

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-18 DOI: 10.1002/jbt.70034

Zhirong Zhu, Guiliang Tang, Mengqi Shi, Mengjie Fang, Xiaolong Zhang, Huali Xu

{"title":"Identification of the Oncogenic Role of the Circ_0001326/miR-577/VDAC1 Cascade in Prostate Cancer","authors":"Zhirong Zhu, Guiliang Tang, Mengqi Shi, Mengjie Fang, Xiaolong Zhang, Huali Xu","doi":"10.1002/jbt.70034","DOIUrl":"10.1002/jbt.70034","url":null,"abstract":"<div>\u0000 \u0000 <p>Prostate cancer (PCa) is one of the leading causes of cancer death among men worldwide. Circular RNAs (circRNAs) have been implicated in the pathogenesis of PCa. However, the precise action of circ_0001326 in PCa malignant progression is still unknown. The levels of circ_0001326, miR-577 and voltage dependent anion channel 1 (VDAC1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation, colony formation, apoptosis, migration and invasion were evaluated by the Cell Counting Kit-8 (CCK-8), EdU staining, colony formation, flow cytometry, wound-healing and transwell assays, respectively. Targeted relationships among circ_0001326, miR-577 and VDAC1 were confirmed by dual-luciferase reporter assays. Xenograft experiments were performed to detect the role of circ_0001326 in tumor growth. Our data revealed that circ_0001326 was overexpressed in PCa tissues and cells. Circ_0001326 depletion repressed PCa cell proliferation, migration, and invasion and enhanced apoptosis in vitro, as well as hampered tumor growth in vivo. Mechanistically, circ_0001326 directly targeted miR-577, and VDAC1 was directly targeted and suppressed by miR-577. Moreover, the effects of circ_0001326 knockdown on PCa cell functional behaviors were mediated by miR-577. VDAC1 silencing phenocopied miR-577 overexpression in regulating PCa cell functional behaviors in vitro. Furthermore, circ_0001326 regulated VDAC1 expression through sponging miR-577. Our findings showed that circ_0001326 regulated PCa cell functional behaviors at least partly through targeting the miR-577/VDAC1 axis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted therapy: P2X3 receptor silencing in bone cancer pain relief 靶向治疗：抑制 P2X3 受体，缓解骨癌疼痛。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-11 DOI: 10.1002/jbt.70026

Yuge Jiang, Xuan Liu, Hong Zhang, Longhe Xu

{"title":"Targeted therapy: P2X3 receptor silencing in bone cancer pain relief","authors":"Yuge Jiang, Xuan Liu, Hong Zhang, Longhe Xu","doi":"10.1002/jbt.70026","DOIUrl":"10.1002/jbt.70026","url":null,"abstract":"<p>Bone cancer pain remains a significant clinical challenge, often refractory to conventional treatments. The upregulation of the P2X3 receptor in the dorsal root ganglia has been implicated in the pathogenesis of bone cancer pain. This study aimed to elucidate the role of the P2X3 receptor in this context and assess the therapeutic potential of receptor silencing. Utilizing a rat model with Walker 256 cells to simulate bone cancer pain, researchers conducted molecular analyses, including semi-quantitative RT-PCR and Western Blot, to investigate P2X3 receptor expression in the dorsal root ganglia. Results demonstrated a marked increase in P2X3 receptor levels in the dorsal root ganglia of the bone cancer pain model. Targeted silencing of the P2X3 receptor using specific shRNA delivered via lentiviral vectors significantly reduced pain sensitivity, underscoring the receptor's potential as a valuable therapeutic target. In addition, a comprehensive gene expression analysis leveraging the GEO data set GSE249443 was performed to explore the underlying biological pathways linked to bone cancer pain. This analysis provided insights into the intricate interplay between bone cancer pain and associated biological processes, offering a deeper understanding of the mechanisms involved in pain modulation and progression. In conclusion, this research identifies the P2X3 receptor as a critical molecular target for mitigating bone cancer pain. The selective silencing of the P2X3 receptor emerges as a promising and innovative therapeutic strategy, presenting novel avenues for managing bone cancer pain and potentially revolutionizing treatment approaches in this challenging domain.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergistic Effect of Salinomycin With Budesonide on TNBC Regression via EMT Reversal and Autophagy Induction 沙林霉素与布地奈德通过EMT逆转和自噬诱导对TNBC消退的协同效应

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-11 DOI: 10.1002/jbt.70045

Shilpi Sarkar, Siddhartha Sankar Ghosh

{"title":"Synergistic Effect of Salinomycin With Budesonide on TNBC Regression via EMT Reversal and Autophagy Induction","authors":"Shilpi Sarkar, Siddhartha Sankar Ghosh","doi":"10.1002/jbt.70045","DOIUrl":"10.1002/jbt.70045","url":null,"abstract":"<div>\u0000 \u0000 <p>Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to its aggressive nature, lack of specific therapeutic targets, and drug resistance. Chemotherapy resistance in TNBC is largely driven by the abnormal activation of epithelial-to-mesenchymal transition (EMT) and the associated cancer stem cell-like characteristics. The combination of multiple chemotherapeutic drugs has shown promise as a treatment approach for TNBC. This study evaluates the efficacy of a novel combination therapy involving the anti-inflammatory drug Budesonide and Salinomycin, which targets cancer stem cells. Co-administration of Budesonide and Salinomycin demonstrated a synergistic effect in inhibiting TNBC cell growth by activating the intrinsic apoptosis pathway. It induced a 2- to 3-fold increase in intracellular reactive oxygen species (ROS) generation and a 25%–30% rise in mitochondrial membrane depolarization. Additionally, extensive signaling studies revealed that the co-treatment specifically targeted multiple signaling nodes, limiting downstream crosstalk. The combination also enhanced autophagic activity by inhibiting the AKT/mTOR pathway and reduced cell migration and stemness by suppressing the EMT process. Therefore, the combination of Budesonide and Salinomycin offers a novel therapeutic approach for TNBC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lactoperoxidase Inhibition of Celecoxib Derivatives Containing the Pyrazole Linked-Sulfonamide Moiety: Antioxidant Capacity, Antimicrobial Activity, and Molecular Docking Studies 含吡唑连接磺酰胺分子的塞来昔布衍生物的乳过氧化物酶抑制作用：抗氧化能力、抗菌活性和分子对接研究。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-11-11 DOI: 10.1002/jbt.70055

Songül Bayrak, Serpil Gerni, Cansu Öztürk, Züleyha Almaz, Çetin Bayrak, Namık Kılınç, Hasan Özdemir

{"title":"Lactoperoxidase Inhibition of Celecoxib Derivatives Containing the Pyrazole Linked-Sulfonamide Moiety: Antioxidant Capacity, Antimicrobial Activity, and Molecular Docking Studies","authors":"Songül Bayrak, Serpil Gerni, Cansu Öztürk, Züleyha Almaz, Çetin Bayrak, Namık Kılınç, Hasan Özdemir","doi":"10.1002/jbt.70055","DOIUrl":"10.1002/jbt.70055","url":null,"abstract":"<p>Celecoxib derivatives that contain the pyrazole-linked sulfonamide moiety were synthesized, and the in vitro inhibitory impacts of the aforesaid compounds against the lactoperoxidase (LPO) enzyme were researched. To this end, LPO was purified using the affinity chromatography technique with a yield of 12.63% (319.23-fold). The results showed that the aromatic pyrazole compound (compound <b>1</b>) containing 2,3-dimethoxyphenyl functional groups was the most effective LPO inhibitor with a K<sub>i</sub> value of 3.2 ± 0.7 nM and noncompetitive inhibition type. The second section of the study tested the previously synthesized compounds to reveal their antioxidant and antimicrobial properties. The above-mentioned compound also displayed high activity levels compared to standard antibiotics and antifungals, while all other compounds also showed antibacterial activity. In the three antioxidant methods we used, the compound with 2,5-dimethoxy phenyl groups obtained from the reaction of the aromatic pyrazole compound with propionic anhydride in the presence of NEt<sub>3</sub> displayed the highest activity. Furthermore, molecular docking and molecular mechanics studies were conducted to complement and validate the experimental findings. The results obtained from these computational analyses are highly consistent with the experimental data.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0