Chemical Biology & Drug Design最新文献

{"title":"Synthesis, Anti-Fibrotic Activity, and Density Functional Theory Calculations of Novel Carboxylic Acid Analogs Containing Pyrrole and Imidazole Rings","authors":"Hiruni Nilshi Indeevarie Abeysiriwardhana,&nbsp;Jin-Hyuk Choi,&nbsp;Ayusha Malla,&nbsp;Yoongho Lim,&nbsp;Chulhun Park,&nbsp;Sang-Soep Nahm,&nbsp;Moonjae Cho","doi":"10.1111/cbdd.70163","DOIUrl":"https://doi.org/10.1111/cbdd.70163","url":null,"abstract":"<div>\u0000 \u0000 <p>Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited treatment options and poor prognosis. Current therapies, Pirfenidone and Nintedanib, slow disease progression but cannot reverse established fibrosis, underscoring the urgent need for innovative strategies. Oxidative stress and hypoxia-inducible factor-1α (HIF-1α) signaling are central to IPF pathogenesis, where the interplay between reactive oxygen species (ROS), TGF-β1, and stabilized HIF-1α forms a self-perpetuating loop that promotes fibroblast activation and extracellular matrix (ECM) deposition. To interrupt this pathological cycle, we rationally designed and synthesized four small molecules, two imidazole- and two pyrrole-based derivatives, with dual antioxidants and HIF-1α inhibitory potential. Their antioxidant potential was assessed using DPPH and DCFDA assays, while density functional theory (DFT) calculations and ADME profiling confirmed their chemical stability and drug-likeness. In vitro screening identified compound <b>2a</b> as the lead candidate based on its superior ability to inhibit HIF-1α and suppress fibrotic markers, including collagen III, fibronectin, and vimentin, in TGF-β1-stimulated A549 and MRC-5 cells. In vivo, <b>2a</b> significantly attenuated collagen and fibronectin accumulation in a bleomycin-induced pulmonary fibrosis model. Mechanistically, 2a inhibited phosphorylation of Smad3 and ERK, implicating modulation of both Smad and non-Smad pathways in its anti-fibrotic effects. These findings position compound <b>2a</b> as a promising dual-targeted therapeutic candidate for IPF, capable of disrupting the ROS–TGF-β1–HIF-1α axis and addressing key unmet clinical needs.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853784","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 New Glycometronidazole Compounds With Antifungal and Antifungal Biofilm Activity","authors":"Rayssa de Cassia Alves Iemini,&nbsp;Ana Laura Marques Trinca,&nbsp;Monique Dias Benedetti,&nbsp;Cleydson Finotti Cordeiro,&nbsp;Alessandro Vieira Ferreira,&nbsp;Amanda Latércia Tranches Dias,&nbsp;Ivo Santana Caldas,&nbsp;Jamie Anthony Hawkes,&nbsp;Diogo Teixeira Carvalho,&nbsp;Lucas Lopardi Franco","doi":"10.1111/cbdd.70154","DOIUrl":"https://doi.org/10.1111/cbdd.70154","url":null,"abstract":"<p>Carbohydrates are well known to be one of the most abundant and structurally diverse natural organic compounds, and they are of great importance as an energy source and as structural components of cell walls in different organisms. They are involved in various biological and pathological processes, including homeostasis, cell–cell interaction, cell migration, cell development, bacterial and viral infection, inflammation, immunology, and cancer metastasis. The variety of these properties is a result of the structural diversity found in carbohydrates. The chemistry of carbohydrates involved in the diagnosis and treatment of diseases has attracted increasing attention from researchers, which is why they should be one of the main focuses in new drug discovery. This study focuses on the synthesis of new glycotriazole–metronidazole compounds as antifungal agents and antifungal biofilm agents, from the glycosylation of metronidazole with various carbohydrates (<span>d</span>-glucose, <span>d</span>-galactose, <span>d</span>-<i>N</i>-acetylglucosamine, and <span>d</span>-lactose). Our hypothesis is that the glycosides could be taken into fungal biofilms through recognition by glycoreceptors and transporters, carrying the active residue with them. In a low-oxygen environment, the nitro group would then undergo bioreduction leading to the formation of toxic radicals potentially resulting in the destruction or paralysis of biofilm formation—essentially functioning as a bioactive “Trojan horse.” The compounds were obtained via a click chemistry reaction using a triazole connector, and the subsequent antifungal tests showed good results for a number of compounds. In silico studies demonstrated positive data for all synthesized compounds, and, in general, they present low toxicological risks.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814605","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":"Inhibition Effects of Patchouli Alcohol, Carvacrol, p-Cymene, Eucalyptol and Their Formulations Against Influenza Virus Pneumonia Through TLR4/NF-κB/NLRP3 Signaling Pathway","authors":"Ruilin Lv,&nbsp;Yi Li,&nbsp;Yinming Zhao,&nbsp;Qi Zhang,&nbsp;Xiaofang Wu,&nbsp;Xingyu Zhao,&nbsp;Linze Li,&nbsp;Ruying Tang,&nbsp;Jianjun Zhang,&nbsp;Linyuan Wang","doi":"10.1111/cbdd.70150","DOIUrl":"https://doi.org/10.1111/cbdd.70150","url":null,"abstract":"<p>As a kind of drug mostly used historically to treat epidemics, aromatic botanicals have volatile oils as active components. The study aims to evaluate the anti-influenza viral pneumonia effects of volatile monomers patchouli alcohol (PA), carvacrol (CV), <i>p-</i>Cymene (PC), eucalyptol (EC) and their formulations from various aspects through the influenza virus A/PR/8/34 (H1N1) infection experiment in vivo and in vitro and carry out in-depth studies on the anti-inflammatory mechanisms. In this study, we found that all four volatile monomers mentioned above could exert antiviral effects by suppressing pulmonary viral load and lung index and improving lung lesions in mice with influenza pneumonia. In addition, elevated levels of cytokines and chemokines in the serum were suppressed, the proportion of T-lymphocytes in the peripheral blood was altered, and antioxidative stress indices were improved, whose mechanism of action related to anti-inflammation, possibly acting on the Toll-Like Receptor 4/Nuclear Factor-κB/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (TLR4/NF-κB/NLRP3) pathway. The study provides an experimental basis for volatile monomers and their formulations of aromatic herbs for treating influenza virus pneumonia.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767803","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":"Repurposing of FDA-Approved Drugs to Disrupt Iron Uptake in Mycobacterium abscessus: Targeting Salicylate Synthase as a Novel Approach","authors":"Giovanni Stelitano,&nbsp;Christian Bettoni,&nbsp;Matteo Mori,&nbsp;Mario Cocorullo,&nbsp;Andrea Tresoldi,&nbsp;Fiorella Meneghetti,&nbsp;Stefania Villa,&nbsp;Laurent R. Chiarelli","doi":"10.1111/cbdd.70162","DOIUrl":"https://doi.org/10.1111/cbdd.70162","url":null,"abstract":"<p>Non-tuberculous mycobacteria (NTM) are opportunistic pathogens that lead to severe, persistent infections, particularly in immunocompromised or vulnerable individuals. Infection rates are rising worldwide, highlighting NTM as an increasing threat to public health. There are currently no specific drugs, and the recommended regimens are usually ineffective. This scenario underlines the urgent need to develop new strategies to effectively combat these infections in a more innovative way. However, the development of new drugs can be a lengthy process, often taking more than a decade to identify even a single active compound. Among the new strategies that can expedite this process is the repurposing of approved drugs. In this work, we applied this approach to identify compounds inhibiting iron uptake in <i>Mycobacterium abscessus</i> (<i>Mab</i>). Specifically, we studied the targeting of salicylate synthase, an enzyme that plays a crucial role in the biosynthesis of mycobacterial siderophores necessary for iron acquisition. Performing an <i>in silico</i> virtual screening of three databases against the crystal structure of salicylate synthase, we identified 11 potential ligands. Then, in vitro assays on the recombinant enzyme highlighted three competitive inhibitors, namely fostamatinib, esomeprazole, and hydroxystilbamidine. These results confirm the potential of the repurposing approach and pave the way for further experimental validation and optimization of these inhibitors as promising compounds against NTM infections.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716932","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":"Synthesis and Bioactivity Evaluation of Novel Sulfonamide-1,2,3-Triazole Hybrids: In Vitro and In Silico Studies","authors":"Mustafa Çeşme,&nbsp;Sultan Onur,&nbsp;Fatma Betül Özgeriş,&nbsp;Ferhan Tümer","doi":"10.1111/cbdd.70155","DOIUrl":"https://doi.org/10.1111/cbdd.70155","url":null,"abstract":"<p>Novel hybrid compounds, incorporating 4-iodosulfonamide and 1,2,3-triazole units, were synthesized and characterized using FT-IR, NMR, and elemental analysis. Their antioxidant (ABTS, DPPH, Cuprac), cholinesterase inhibition (AChE, BuChE), and anticancer (Caco-2, PC3) activities were evaluated. In DPPH assays, compounds 13, 6, and 11 showed superior antioxidant activity compared to α-tocopherol and BHT. Compound 6 exhibited the highest ABTS activity, while compound 9 excelled in Cuprac assays. For cholinesterase inhibition, compounds 8 and 13 outperformed Galantamine against AChE, and compound 9 showed the strongest BuChE inhibition. Antiproliferative studies revealed compound 13's effectiveness against PC3 and compound 9 against Caco-2. Comprehensive ADMET analysis indicated favorable pharmaceutical properties, including oral absorption via the BBB and GI tract. In silico molecular docking supported these findings, confirming the therapeutic potential of these hybrid structures.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705673","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":"2-Hydroxy-3-Methylanthraquinone Suppresses Hepatocellular Carcinoma Progression by Blocking Annexin A5-Mediated Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling","authors":"Min Luo,&nbsp;Juanmei Mo,&nbsp;Chaoyuan Huang,&nbsp;Yan Mao,&nbsp;Hongzhi Wang,&nbsp;Xiaochen Wang","doi":"10.1111/cbdd.70161","DOIUrl":"https://doi.org/10.1111/cbdd.70161","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC), the most common subtype of primary liver cancer, remains a major cause of cancer-related mortality worldwide. Although 2-hydroxy-3-methylanthraquinone (HMA), a natural anthraquinone compound, has demonstrated antitumor activity in various malignancies, its specific role and underlying mechanisms in HCC are not fully understood. This study aimed to evaluate the antitumor effects and molecular mechanisms of HMA in HCC. Human HCC cell lines were treated with HMA, and cell proliferation and apoptosis were assessed using Cell Counting Kit-8 and flow cytometry assays, respectively. A heterotopic xenograft tumor model was established in nude mice to evaluate in vivo tumor growth and weight. Immunohistochemical staining for Ki67 and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to assess tumor cell proliferation and apoptosis. Network pharmacology analysis was conducted to predict potential targets of HMA in HCC. Quantitative real-time polymerase chain reaction and Western blotting were used to evaluate mRNA and protein expression levels. Cell migration and invasion were assessed using wound healing and transwell assays. Our data revealed that HMA significantly suppressed cell proliferation, induced apoptosis, and inhibited migration and invasion in both HCC cells and tumor tissues. Mechanistically, HMA downregulated Annexin A5 (ANXA5) expression and inhibited activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. Silencing of ANXA5 replicated the inhibitory effects of HMA and further enhanced its pro-apoptotic and anti-invasive activities. Conversely, overexpression of ANXA5 restored PI3K/AKT signaling activity and reversed the inhibitory effects of HMA on HepG2 cell proliferation, migration, and invasion. These reversal effects were abolished by treatment with LY294002, a selective PI3K inhibitor. In summary, HMA suppresses the progression of HCC by targeting ANXA5 and inhibiting the PI3K/AKT signaling pathway, highlighting its potential as a novel therapeutic agent for HCC.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688014","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":"Correction to “Improving Classical Scoring Functions Using Random Forest: The Non-Additivity of Free Energy Terms’ Contributions in Binding”","authors":"","doi":"10.1111/cbdd.70159","DOIUrl":"https://doi.org/10.1111/cbdd.70159","url":null,"abstract":"<p>Karim Afifi, Ahmed Farouk Al-Sadek. Improving classical scoring functions using random forest: The non-additivity of free energy terms’ contributions in binding. <i>Chemical Biology &amp; Drug Design</i>. 2018;92: 1429-1434. https://doi.org/10.1111/cbdd.13206</p><p>In the article, Ahmed Farouk Al-Sadek's affiliation has been incorrectly provided as “Central Lab for Agricultural Experts Systems, Ministry of Agriculture and Land Reclamation, Giza, Egypt.” However, it should be “Central Lab for Agricultural Experts Systems, Agricultural Research Center (ARC), Giza, Egypt.”</p><p>The author apologizes for this error.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681549","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":"Correction to “Synthesis and Activity Study of Gefitinib Derivatives Inducing Mitochondrial Apoptosis in HeLa Cells”","authors":"","doi":"10.1111/cbdd.70160","DOIUrl":"https://doi.org/10.1111/cbdd.70160","url":null,"abstract":"<p>Li, Y., Hou, X., Liu, S., Chen, Z., Wu, Q., He, B., Guo, J., Wang, L., Liu, C., Fei Mao, L. 2024. “Synthesis and Activity Study of Gefitinib Derivatives Inducing Mitochondrial Apoptosis in HeLa Cells.” <i>Chemical Biology and Drug Design</i> 104, no. 6: e70035.</p><p>The first affiliation was mistakenly listed as <b>Zhoukou Center Hospital</b>; however, the correct name should be <b>Zhoukou Central Hospital</b>.</p><p>The authors apologize for this error.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681545","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":"Spalt-Like Transcription Factor 4 Mediates Fatty Acid Oxidation to Foster 5-Fluorouracil Resistance in Gastric Cancer Cells","authors":"Yong Zhu,&nbsp;Chuanmin Yi,&nbsp;Jin Zhao,&nbsp;Lei Wang,&nbsp;Tao Huang,&nbsp;Bo Xiang,&nbsp;Lvhai Zhang,&nbsp;Xiangfang He,&nbsp;Linke Wu","doi":"10.1111/cbdd.70158","DOIUrl":"https://doi.org/10.1111/cbdd.70158","url":null,"abstract":"<div>\u0000 \u0000 <p>Platinum-based and pyrimidine drugs are first-line treatments for gastric cancer (GC), but their efficacy is often affected by drug resistance. High spalt-like transcription factor 4 (SALL4) expression is associated with poor prognosis, but its role in 5-fluorouracil (5-FU) resistance is not yet clear. In this study, we investigated the effect of SALL4 on 5-FU resistance in GC cells by bioinformatics analysis, real-time quantitative reverse transcription polymerase chain reaction, cell counting kit-8, colony formation assay, and western blot. The results showed that SALL4 was highly expressed in GC and significantly correlated with the fatty acid oxidation (FAO) pathway. Knockdown of SALL4 resulted in a notable attenuation of cellular proliferative capacity and heightened susceptibility to 5-FU resistance in GC cells, while overexpression of SALL4 enhanced 5-FU resistance. Rescue assays confirmed that SALL4 fostered 5-FU resistance in GC cells by enhancing FAO. Our research confirmed that SALL4 promoted the resistance of GC cells to 5-FU by enhancing the FAO pathway. This suggests that drug development targeting SALL4 may help overcome chemotherapy resistance in GC.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688067","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":"New Thiadiazole-Benzenesulfonamide Hybrids as Dual B-Raf/VEGFR-2 Inhibitors With Promising Anti-Hepatic Cancer Activity","authors":"Aisha A. Alsfouk,&nbsp;Hazem Elkady,&nbsp;Saber M. Hassan,&nbsp;Walid E. Elgammal,&nbsp;Hazem A. Mahdy,&nbsp;Dalal Z. Husein,&nbsp;Fatma G. Amin,&nbsp;Mohamed Hagras,&nbsp;Eslam B. Elkaeed,&nbsp;Ahmed M. Metwaly,&nbsp;Ibrahim H. Eissa","doi":"10.1111/cbdd.70156","DOIUrl":"https://doi.org/10.1111/cbdd.70156","url":null,"abstract":"<div>\u0000 \u0000 <p>A new group of thiadiazole-benzenesulfonamide hybrids was designed, synthesized, and biologically evaluated as potential dual inhibitors targeting B-Raf and VEGFR-2 for cancer therapy. The cytotoxic activity of the synthesized derivatives was assessed against HepG2 and Huh7 liver cancer cell lines, where compound <b>7a</b> exhibited the most potent activity with IC₅₀ values of 17.89 μM and 25.07 μM, respectively. The kinase inhibition assay revealed that <b>7a</b> strongly inhibited both B-Raf (IC₅₀ = 0.11 μM) and VEGFR-2 (IC₅₀ = 0.15 μM), surpassing sorafenib in B-Raf inhibition. Further mechanistic studies revealed that <b>7a</b> induced G2/M phase arrest, with a significant increase in late apoptotic cells (57.08%) compared to the control group (0.15%), confirming its pro-apoptotic effect. The apoptotic pathway was further validated by caspase-3 activation, Bax upregulation, and Bcl-2 downregulation. Computational analyses verified the effective binding of compound <b>7a</b> to VEGFR-2. These analyses included molecular docking, molecular dynamic (MD) simulations, molecular mechanics with generalized Born and surface area solvation (MM-GBSA), protein-ligand interaction fingerprints (ProLIF), principal component analysis (PCAT), and free energy landscape (FEL) studies. Additionally, DFT studies indicated <b>7a</b>'s stability and reactivity. <i>In silico</i> ADMET predictions indicated that the derivatives had good absorption, were non-mutagenic, non-carcinogenic, and exhibited low toxicity risks compared to sorafenib. These findings suggest that the synthesized thiadiazole-benzenesulfonamide hybrids, particularly <b>7a</b>, represent promising dual BRAF/VEGFR-2 inhibitors with potent anti-cancer activity, warranting further optimization and preclinical evaluation.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666222","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}