Chemical Biology & Drug Design最新文献

{"title":"A Naturally Derived Glycosylated Oleanolic Acid Derivative Suppresses NF-κB Translocation and Induces Intrinsic Apoptosis in Lung Adenocarcinoma Cells","authors":"Sankar Pajaniradje,&nbsp;Srividya Subramanian,&nbsp;Kumaravel Mohankumar,&nbsp;Larance Ronsard,&nbsp;Parthiban Anaikutti,&nbsp;Rukkumani Rajagopalan","doi":"10.1111/cbdd.70137","DOIUrl":"https://doi.org/10.1111/cbdd.70137","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigates the molecular mechanism of action of F4B1, a novel oleanolic acid derivative in human lung adenocarcinoma cells. F4B1 is a naturally occurring oleanolic acid derivative that was isolated and purified from the leaves of <i>Sesbania grandiflora</i>. Structural analyses were carried out using 1D and 2D NMR, FT-IR, and mass spectrometric analyses. MTT assay was employed to evaluate antiproliferative effects in A549 (a model for lung cancer), MCF-7 (a model for breast cancer), HEP-2 (a model for head and neck cancer) and in MRC-5 (human lung fibroblast cells). Fluorescence staining, scanning electron microscopy, and flow cytometry were employed to study apoptosis and cell cycle. Western blotting, RT-PCR, and immunofluorescence techniques were followed to study the mechanisms of cell death. Schrodinger software was employed for docking studies. While preliminary screening was conducted in multiple cell lines, A549 cells were chosen for further mechanistic exploration based on their higher sensitivity to F4B1 treatment. F4B1 blocks the proliferation and causes intrinsic mode of cell death in lung adenocarcinoma cells. In particular, the above anticancer effect was mediated through a mechanism that is associated with the inactivation of NF-kappa B signaling and suppression of cyclin D1 expression leading to cell cycle arrest at the G1/S phase. Our study confirms that F4B1 induces apoptosis, as confirmed through Annexin V staining results. It is intrinsic apoptosis, as evidenced by upregulation of pro-apoptotic markers (BAX), downregulation of anti-apoptotic markers (BCL-2), cytochrome C release, activation of caspase-9, and caspase-3. These results establish the involvement of the mitochondrial-mediated apoptotic pathway. The pathway also involved the suppression of the proto-oncogene c-Myc both at the transcriptional and translational levels. Docking studies show that F4B1 has a high affinity binding towards CXCR4 and SRC kinase. Our findings specifically contribute to understanding the mechanism of F4B1, the isolated molecule from <i>S. grandiflora,</i> as an anticancer drug candidate and will hopefully pave the way toward further studies.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kisspeptin-54 Restores Blood–Brain Barrier Integrity via GATA-4 in Ischemic Stroke","authors":"Weifeng Shan,&nbsp;Haiyan Lan,&nbsp;Yini Wu,&nbsp;Qiaomin Xu,&nbsp;Minji You,&nbsp;Ruijun Ma","doi":"10.1111/cbdd.70134","DOIUrl":"https://doi.org/10.1111/cbdd.70134","url":null,"abstract":"<div>\u0000 \u0000 <p>Ischemic stroke damages the blood–brain barrier (BBB), worsening neuronal injury. Treatments to protect the BBB are limited. We evaluated the neurovascular protective capacity of Kisspeptin-54 in ischemic stroke using in vivo and in vitro models. In vivo, mice underwent middle cerebral artery occlusion (MCAO), and cerebral infarct volume, neurological function, and blood–brain barrier (BBB) permeability were evaluated. In vitro, human brain microvascular endothelial cells (HBMVECs) were exposed to oxygen–glucose deprivation/reperfusion (OGD/R) to assess the effects of Kisspeptin-54 on paracellular flux and transendothelial electrical resistance (TEER). Additionally, GATA-4 was silenced to investigate its role in mediating protection. Our results showed that cortical ischemia downregulated KISS-1 metastasis-suppressor (KISS1, 59% mRNA; 55% protein) and G protein-coupled receptor 54 (GPR54, 54% mRNA; 48% protein), with a 32% decline in circulating Kisspeptin-54. Prophylactic Kisspeptin-54 reduced cerebral infarct volume by 42%, enhanced neurological performance by 49%, and decreased BBB leakage by 26%, with near-complete occludin recovery. In vitro: Kisspeptin-54 treatment reduced paracellular flux by 48% and increased transendothelial resistance by 60%. GATA-4 silencing abolished Kisspeptin-54-induced occludin restoration, increasing permeability by 65% and diminishing barrier resistance by 28%. This study reveals Kisspeptin-54 modulates BBB stability via GATA-4-driven occludin expression, highlighting the KISS1/GPR54 pathway as a potential therapeutic target for ischemic stroke.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, and Biological Activity of 8-Hydroxyurolithin A Class PDE2 Inhibitors","authors":"Qiulin Hu,&nbsp;Long Tang,&nbsp;Zhongqiu Xu,&nbsp;Fen Yan,&nbsp;Guoqiang Song,&nbsp;Xiaoqing Feng","doi":"10.1111/cbdd.70119","DOIUrl":"https://doi.org/10.1111/cbdd.70119","url":null,"abstract":"<div>\u0000 \u0000 <p>Urolithin A (UA) is a dibenzo[<i>b,d</i>]pyran-6-one polyhydroxy derivative produced as intestinal microbe metabolize ellagitannin and ellagic acid. Because of its superior anti-inflammatory and antioxidant effects, it can cure neuronal damage in a variety of ways and play a neuroprotective role. More and more research has revealed that UA is a potential medicine for the treatment of neurodegenerative diseases. Due to UA source limitations, it is insufficient to achieve disease treatment concentrations, and the activity of UA inhibiting PDE2 needs further enhancement. As a result, we used UA as the parent nucleus structure, independently designed and used Discovery Studio software to assist in the structural design and molecular docking screening of the compounds, and tested the in vitro enzyme activity of the synthesized compounds, hoping to obtain UA-based PDE2 inhibitors. The IC₅₀ of 6–18, 6–19, 6–20, 6–22, and 6–29 were 0.62, 0.85, 1.51, 1.09, and 1.58 μM, respectively. In this study, UA derivatives that can bind to the crystal structure of PDE2 protein 4HTX were proposed, which laid a groundwork for further structural modification, lead design, and development of small molecule inhibitors with inhibitory activity of PDE2.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Novel Thiazole/Thiadiazole Conjugates of Fluoroquinolones as Potent Antibacterial and Antimycobacterial Agents","authors":"Pınar Poyraz Yılmaz,&nbsp;Necla Kulabaş,&nbsp;Arif Bozdeveci,&nbsp;Siva Krishna Vagolu,&nbsp;Mohd Imran,&nbsp;Esra Tatar,&nbsp;Şengül Alpay Karaoğlu,&nbsp;Dharmarajan Sriram,&nbsp;Ammar A. Razzak Mahmood,&nbsp;İlkay Küçükgüzel","doi":"10.1111/cbdd.70126","DOIUrl":"https://doi.org/10.1111/cbdd.70126","url":null,"abstract":"<p>Twenty azole-fluoroquinolone hybrids were designed and synthesized by conjugating thiazole and thiadiazole structures to ciprofloxacin and norfloxacin via a 2-oxoethyl bridge. The structures and purities of the synthesized compounds were proven by spectral techniques. The antimycobacterial effects of target compounds <b>21–40</b> were tested against <i>Mycobacterium tuberculosis</i> H37Rv strain. Among the 20 synthesized compounds, 12 exhibited minimal inhibition concentration (MIC) values in the range of 1.56–25 μg/mL. Among the molecules screened for antimycobacterial effects, the most effective was compound <b>35</b>, a thiadiazole-ciprofloxacin hybrid. The cytotoxic effect of this molecule was found to be lower than the reference drugs, and it was also determined to be a more effective inhibitor than ciprofloxacin and norfloxacin in the DNA-gyrase supercoiling test. The antimicrobial effects of compounds <b>21–40</b> were screened by agar-well diffusion and microdilution tests against Gram-positive/negative bacteria, a fast-growing mycobacterium, and two yeast strains. While most of the compounds tested showed antibacterial effects, the most effective fluoroquinolone derivative appeared to be compound <b>31</b> with an MIC value of &lt; 0.63 μg/mL against all Gram-negative bacteria tested. Azole-fluoroquinolone hybrids <b>21–40</b> did not show any activity against non-pathogenic <i>Lactobacillus</i> species and yeast-like fungi, indicating that they have selective antibacterial and antimycobacterial activity, particularly against Gram-negative bacteria. <i>In silico</i> molecular docking studies were conducted to uncover the interactions between lead compound <b>35</b> and the DNA gyrase proteins of <i>M. tuberculosis</i> and <i>S. aureus</i>. Additionally, a 100 ns molecular dynamics simulation was carried out to assess the stability of the complexes formed between compound <b>35</b> and both proteins.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis and Biological Evaluation of POLRMT Inhibitors for the Treatment of Acute Myeloid Leukemia","authors":"Tianli Liu,&nbsp;Xiaoling Cheng,&nbsp;Yupeng Wang,&nbsp;Wenli Hao,&nbsp;Hangyu Wang,&nbsp;Ke Zhang,&nbsp;Jinhui Wang","doi":"10.1111/cbdd.70127","DOIUrl":"https://doi.org/10.1111/cbdd.70127","url":null,"abstract":"<div>\u0000 \u0000 <p>The metabolic dependence of acute myeloid leukemia (AML) cells on mitochondrial oxidative phosphorylation (OXPHOS) has become a cutting-edge area in cancer energy metabolism research, playing a pivotal role in cell survival and drug resistance. Consequently, targeted inhibition of human mitochondrial RNA polymerase (POLRMT) to block mitochondrial gene expression emerges as a novel potential strategy for treating AML through OXPHOS modulation. In this study, based on the previously reported crystal structure of the POLRMT inhibitor IMT1B, we employed a scaffold hopping strategy to design and synthesize a series of derivatives featuring additional hydrophobic occupying groups. A new potent POLRMT inhibitor (<b>10a</b>) was discovered, which displayed potent antiproliferative activity and could disrupt mitochondrial function and induce apoptosis in MOLM-13 cells. Together, these results demonstrate that <b>10a</b> is a new POLRMT inhibitor, which may provide a candidate lead for AML treatment.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and Synthesized 3,4-Dimethoxybenzene-Based Fibrate Derivatives as Potential Hypolipidemic and Liver Protection Agents","authors":"Ling Ding,&nbsp;Yuyu An,&nbsp;Xinyi Shi,&nbsp;Huizi Shangguan,&nbsp;Xin Wang,&nbsp;Jiping Liu,&nbsp;Yongheng Shi,&nbsp;Xinya Xu,&nbsp;Yundong Xie","doi":"10.1111/cbdd.70123","DOIUrl":"https://doi.org/10.1111/cbdd.70123","url":null,"abstract":"<div>\u0000 \u0000 <p>A series of 3,4-dimethoxybenzene-based fibrate derivatives were designed and synthesized, which were screened for preliminary lipid-lowering activity in a Triton WR-1339-induced hyperlipidemic mouse model. T5 had the strongest triglyceride (TG) and total cholesterol (TC) lowering effect among these target compounds. In a dose-dependent study, the lowering effects of T5 on TG and TC were progressively enhanced with increasing doses administered. Further studies revealed that T5 had a hypolipidemic significant effect on high-fat diet (HFD)-induced hyperlipidemia mouse model, with substantial reductions in TG, TC, and low-density lipoprotein cholesterol (LDL-C) levels, and a significant reduction in aspartate transaminase (AST) and alanine aminotransferase (ALT) levels in the liver, which had a protective effect on the liver. The of liver pathology showed that T5 could effectively inhibit lipid accumulation as well as inflammatory infiltration in the liver, thus reducing the degree of liver tissue damage. The expression of peroxisome proliferator-activated receptor-α (PPAR-α), which regulates lipid metabolism, was significantly upregulated in liver tissues. Molecular docking assays also confirmed the high binding affinity between T5 and PPAR-α active sites. In addition, T5 exhibited significant anti-inflammatory and antioxidant effects. These findings suggest that T5 has multiple activities and may be a potential novel hypolipidemic drug with hypolipidemic and hepatoprotective effects.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144117993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of Novel Inhibitors for WD Repeat-Containing Protein 5 (WDR5)-MYC Protein–Protein Interaction","authors":"Wei Sun,&nbsp;Huaxing Yu,&nbsp;Jiuyong Ye,&nbsp;Luoheng Qin,&nbsp;Linli Wang,&nbsp;Hailu Yan,&nbsp;Zhimin Zhang,&nbsp;Alex Aliper,&nbsp;Feng Ren,&nbsp;Xiao Ding,&nbsp;Alex Zhavoronkov,&nbsp;Dongzhou Liu","doi":"10.1111/cbdd.70129","DOIUrl":"https://doi.org/10.1111/cbdd.70129","url":null,"abstract":"<div>\u0000 \u0000 <p>The WD Repeat-Containing Protein 5 (WDR5) and MYC interaction is crucial for MYC-mediated oncogenesis, yet effective therapeutic intervention remains challenging due to the limited efficacy of current treatments targeting WDR5. Herein, we report the discovery of novel WDR5-MYC protein–protein interaction (PPI) inhibitors with improved potency and drug-like properties by utilizing a generative chemistry platform along with a physics-model-based tool AlChemistry. Initially, three hits were identified with reasonable binding affinity for WDR5, and further refinement through detailed structural analysis led to the discovery of sub-micromolar affinity compounds (compound <b>9c-1</b>), which are &gt; 30-fold better than reported inhibitors. These findings provide a promising starting point for targeting the WDR5-MYC interaction in MYC-driven cancers.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Phenoxyacetic Acid (4-Aminophenoacetic Acid) Shikonin Ester Kills KRAS Mutant Colon Cancer Cells via Targeting the Akt Allosteric Site","authors":"Yudi Ma,&nbsp;Yuqian Sun,&nbsp;Qingqing Tu,&nbsp;Faxiang Lin,&nbsp;Feng Mei,&nbsp;Qingqing Chen,&nbsp;Ting Fu,&nbsp;Liu Yang,&nbsp;Xiaohui Lai,&nbsp;Minkai Yang,&nbsp;Tongming Yin,&nbsp;Guihua Lu,&nbsp;Jinliang Qi,&nbsp;Hongyan Lin,&nbsp;Zhongling Wen,&nbsp;Yonghua Yang,&nbsp;Hongwei Han","doi":"10.1111/cbdd.70125","DOIUrl":"https://doi.org/10.1111/cbdd.70125","url":null,"abstract":"<div>\u0000 \u0000 <p>The PI3K-Akt axis is abnormally activated in KRAS-mutated colorectal cancer and is considered to be a potential therapeutic target. A novel series of phenoxyacetic acid (4-aminophenoacetic acid) shikonin esters was designed by computer-aided drug design (CADD) and synthesized as Akt allosteric inhibitors. Most compounds exhibited greater anti-proliferative activity compared to the positive control MK2206, while also demonstrating lower cytotoxicity against normal cells than shikonin. One of the promising candidates, L8, was selected for further biological evaluation. Docking studies indicated that L8 effectively bound to the allosteric site of Akt through hydrophobic and hydrogen interactions. Enzyme activity and kinetics assessments revealed that L8 bound to Akt with a Kd of 2.07 × 10⁻⁶ M and inhibited its activity. Further intracellular assays, including western blotting, enzyme activity assay, flow cytometry, etc., verified that L8 mediated the death of two KRAS-mutant colon cancer cell lines HCT116 (KRAS^G13D) and HCT-8 (KRAS^G12A) cells by inactivating Akt, causing tumor cell apoptosis, cell cycle arrest, and interfering with tumor cell invasion and metabolism. A 3D-QSAR model was constructed to understand the relationship between the structure of the shikonin derivatives and their anti-proliferative activity. The in silico ADMET and toxicity prediction studies revealed a few undesired pharmacokinetic attributes of our compounds.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis Methods and Therapeutic Journey of Carprofen and Its Derivatives: A Review","authors":"Carmen Limban,&nbsp;Diana Camelia Nuță,&nbsp;Miron Teodor Caproiu,&nbsp;Denisa Elena Dumitrescu,&nbsp;Șerban Iancu Papacocea,&nbsp;Alexandra Teodora Bordei,&nbsp;Florea Dumitrașcu","doi":"10.1111/cbdd.70122","DOIUrl":"https://doi.org/10.1111/cbdd.70122","url":null,"abstract":"<p>Carprofen, a nonsteroidal anti-inflammatory drug (NSAID) derived from propanoic acid, is known for its analgesic and antipyretic properties. Although it has long been employed in veterinary medicine as an anti-inflammatory agent, its use in humans was discontinued shortly after its market launch due to costly raw materials, complex synthesis, and labor-intensive production processes—factors that made it less competitive compared with other NSAIDs. Despite this, the carprofen molecule remains a subject of significant scientific interest. Recent advancements in its synthesis have introduced simplified and more cost-effective methods, reigniting its potential for both novel applications and drug repurposing. Exciting new research is exploring carprofen's broader therapeutic possibilities, extending beyond its original anti-inflammatory role. Studies are investigating its efficacy in antimicrobial therapy—including antibiofilm, anticancer, antiviral, and anti-Alzheimer's applications—opening doors to a wealth of untapped possibilities. This review delves into these emerging areas, highlighting how carprofen's molecular structure and derivatives can be leveraged to expand its therapeutic reach. The literature review was conducted using four databases: Web of Science, ScienceDirect, Scopus, Embase, and Reaxys. The review focused on English-language original research and review articles, examining carprofen and its derivatives in terms of their synthesis methods as well as their use as small molecules in various therapeutic applications, both human and veterinary. With ongoing research pushing the boundaries of its potential, carprofen remains a promising candidate for innovation in drug development and treatment strategies.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review on the Advancements of Dual COX-2/5-LOX Inhibitors as Anti-Inflammatory Drugs","authors":"Neetu Agrawal","doi":"10.1111/cbdd.70114","DOIUrl":"https://doi.org/10.1111/cbdd.70114","url":null,"abstract":"<div>\u0000 \u0000 <p>Chronic pain and inflammation are widespread clinical issues that significantly affect patients' quality of life and are often associated with serious conditions such as arthritis, cancer, and cardiovascular disease. Effective management of inflammation is therefore a major public health priority. Current anti-inflammatory treatments—including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biologics—offer symptomatic relief but are frequently limited by side effects such as gastrointestinal toxicity, immunosuppression, or cardiovascular risks. Moreover, most of these therapies target only a single pathway in the inflammatory cascade. Dual inhibitors of COX-2 and 5-LOX have emerged as a promising therapeutic class, as they simultaneously block two key enzymes involved in prostaglandin and leukotriene synthesis. This dual-action approach offers enhanced efficacy and may reduce adverse effects linked to selective or non-selective COX inhibition. This review discusses the underlying mechanisms of inflammation, evaluates current treatment options, and highlights the pharmacological advantages and development status of dual COX-2/5-LOX inhibitors as a next-generation strategy for inflammation management.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}