Chemical Biology & Drug Design最新文献

{"title":"Discovery of Potent EGFR Inhibitors for Del19 and L858R/T790M Mutants Through Structure-Based Virtual Screening and Biological Evaluation","authors":"Ting Xu,&nbsp;Yuchen Zhao,&nbsp;Mengfei Chen,&nbsp;Lijuan Zuo,&nbsp;Hanshuang Cai,&nbsp;Yuguo Liu,&nbsp;Chuanfeng Liu,&nbsp;Jing Shi","doi":"10.1111/cbdd.70391","DOIUrl":"10.1111/cbdd.70391","url":null,"abstract":"<p>Epidermal growth factor receptor (EGFR) mutation-mediated drug resistance represents a major clinical challenge in the treatment of non-small cell lung cancer (NSCLC). In this study, the lead compound <b>XJ2-2</b> was identified through structure-based virtual screening. It exhibited potent anti-proliferative activity against both EGFR^Del19 mutant PC-9 cells and EGFR^L858R/T790M mutant H1975 cells, with IC₅₀ values of 0.88 ± 0.12 μM and 0.77 ± 0.09 μM, respectively. Mechanistic studies have demonstrated that <b>XJ2-2</b> directly targets and binds to the EGFR, thereby effectively inhibiting EGFR phosphorylation and its downstream signaling pathways in both in vitro and in vivo models. In tumor-bearing mouse models, <b>XJ2-2</b> significantly reduced tumor burden. Preclinical safety evaluation indicated that no treatment-related toxicity was observed for <b>XJ2-2</b> at all tested doses. With its novel molecular scaffold and mutant-selective inhibitory profile, <b>XJ2-2</b> represents a promising lead compound for overcoming NSCLC drug resistance and advancing the development of next-generation EGFR inhibitors.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148932084","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":"Rational Design, Synthesis, Biological Evaluation, and In Silico Study of N-Cinnamamide/Benzamide-(4-(Substituted Phenyl)-6-(4-Cyclohexylphenyl)pyrimidin-2-Yl) Derivatives as EGFR Inhibitors Targeting EGFRWT, EGFRT790M, and EGFRL858R/T790M/C797S in NSCLC","authors":"Rohit Pal,&nbsp;Gurubasavaraja Swamy Purawarga Matada,&nbsp;Ghanshyam Teli,&nbsp;Manjushree BV,&nbsp;Anguraj Moulishankar,&nbsp;Viney Chawla,&nbsp;Pooja A. Chawla","doi":"10.1111/cbdd.70390","DOIUrl":"10.1111/cbdd.70390","url":null,"abstract":"<p>Non-small cell lung cancer (NSCLC), driven by mutations in the epidermal growth factor receptor (EGFR), presents significant therapeutic challenges, particularly due to drug resistance. This study describes the design, synthesis, and evaluation of a series of novel <i>N</i>-Cinnamamide/benzamide-(4-(substituted phenyl)-6-(4-cyclohexylphenyl)pyrimidin-2-yl) derivatives (<b>Ri–Rxii</b>) as EGFR inhibitors. Among these, compound <b>Riv</b> exhibited superior antiproliferative activity against wild-type and mutant EGFR-driven NSCLC cell lines, including EGFR^L858R/T790M and the drug-resistant EGFR^{L858R/T790M/C797S} variant, with low IC₅₀ values and minimal cytotoxicity towards normal cell lines. Compound <b>Riv</b> effectively induced cell cycle arrest at the S and G2/M phases and triggered apoptosis, with 54.38% of cells undergoing apoptotic or necrotic death. Additionally, <b>Riv</b> exhibited strong antioxidant activity, outperforming the standard ascorbic acid in DPPH and ABTS assays, indicating its ability to reduce oxidative stress. Molecular docking and dynamic simulation studies confirmed stable binding interactions with key EGFR residues, and DFT analysis revealed favorable electronic properties. Furthermore, in silico ADMET predictions highlighted <b>Riv</b>'s promising pharmacokinetic and toxicity profiles, supporting its potential as a safe and effective anticancer agent. This comprehensive evaluation positions <b>Riv</b> as a strong candidate for overcoming drug resistance in NSCLC treatment.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914703","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 Anthracene Derivatives as Potent Antioxidants: Experimental, DFT, and Docking Studies","authors":"Mohamed R. Elmorsy,&nbsp;Menna Moustafa,&nbsp;Hassan A. Etman,&nbsp;Nashwa M. El-Metwaly,&nbsp;Safa A. Badawy","doi":"10.1111/cbdd.70392","DOIUrl":"10.1111/cbdd.70392","url":null,"abstract":"<p>A series of 10 anthracene derivatives (<b>MM-1-MM-10</b>), comprising anthracene cyanoacrylamides (<b>MM-1-MM-5</b>) and anthracene hydrazinyl-thiazoles (<b>MM-6-MM-10</b>), was synthesized from anthracene-9-carbaldehyde and characterized by FT-IR, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. The two-family design was used to test whether replacing the cyanoacrylamide linker with a hydrogen-donating hydrazinyl-thiazole unit improves radical-scavenging behavior while retaining the extended anthracene pi-system. Antioxidant activity was evaluated by the DPPH assay using ascorbic acid as the reference. <b>MM-10 and MM-9</b> were the most active compounds, with IC₅₀ values of 0.0033 ± 0.0002 and 0.0053 ± 0.0003 mg/mL, respectively, compared with 0.0164 ± 0.0006 mg/mL for ascorbic acid. MM-7 and MM-6 also showed strong activity, with IC₅₀ values of 0.0123 ± 0.0006 and 0.0162 ± 0.0006 mg/mL, respectively. Gas-phase DFT calculations were performed at the B3LYP/6-311G(d, p) level. An exploratory descriptor-activity analysis across the 10 compounds indicated that donor-related descriptors, particularly the nucleophilicity index (Nu), were more closely associated with DPPH potency than the HOMO-LUMO gap considered alone. Because the data set is small, this correlation is interpreted as hypothesis-generating rather than as a generally predictive model. Docking against the KEAP1 Kelch domain (PDB ID: 8IVR) suggested favorable binding poses for <b>MM-3</b>, <b>MM-7</b>, <b>MM-9</b>, and <b>MM-10</b> relative to the co-crystallized inhibitor. These docking results provide supportive mechanistic hypotheses at the pathway level but do not establish cellular KEAP1 inhibition or biological antioxidant activity. Overall, the experimental data identify the hydrazinyl-thiazole subseries, particularly <b>MM-7</b>, <b>MM-9</b>, <b>and MM-10</b>, as promising scaffolds for further cellular, toxicity, and in vivo evaluation.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901694","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":"Prevotella melaninogenica Alleviate Mycoplasma pneumoniae Infection Through the Butyrate Based on Multi-Omic Analysis and Experimental Validation","authors":"Zhengyang Xue,&nbsp;Huiliang Xu,&nbsp;Ling Zhu,&nbsp;DeYu Zhao","doi":"10.1111/cbdd.70397","DOIUrl":"10.1111/cbdd.70397","url":null,"abstract":"<p><i>Mycoplasma pneumoniae</i> (MP) is one of the main pathogens causing atypical pneumonia in children. The susceptible population is mainly children and adolescents over 5 years old, and the infection rate has increased in recent years. At present, there is limited research on the pulmonary microbiota of patients with <i>Mycoplasma pneumoniae</i> pneumonia, and the characteristics of their microbiota are not yet clear. We included MPP children in stages and established two independent cohorts. Cohort I (<i>n</i> = 175) performed 16S rRNA sequencing on bronchoalveolar lavage fluid (BALF) to explore microbial genus level characteristics, while Cohort II (<i>n</i> = 41) performed metagenomic and transcriptome sequencing to explore microbial species level characteristics and predict inter group differential metabolic pathways. Finally, a murine model infected with MP was established to validate the effects of <i>Prevotella melaninogenica</i> and its metabolite butyrate. Based on Multi-Omic Analysis, we discovered that <i>P. melaninogenica</i> was the most discriminative species enriched in the critically ill group. Functional profiling demonstrated that butanoate metabolism pathways were significantly enriched in the severe group and positively correlated with <i>P. melaninogenica</i> abundance. Transcriptomic analysis revealed that <i>P. melaninogenica</i>-associated host genes were significantly enriched in immune regulation pathways. Animal experiments confirmed that both <i>P. melaninogenica</i> and butyrate pretreatment significantly attenuated MP-induced pulmonary inflammation, pathogen load, and immune cell infiltration. Respiratory microbiota dysbiosis may be associated with MPP severity. <i>Prevotella melaninogenica</i>, a potential protective commensal enriched in severe group MPP patients, may alleviate airway inflammation through its metabolite butyrate.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901723","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":"Discovery of ERα-Targeting Phytochemicals With In Vitro Cytotoxicity and Computational Prediction of Y537S Mutant Inhibition","authors":"Dejun Jiang,&nbsp;Oh Wook Kwon,&nbsp;Hanbin Joe,&nbsp;Euijeong Shin,&nbsp;Sungjoon Cho,&nbsp;Hyuk-Ku Kwon,&nbsp;Youngjin Choi","doi":"10.1111/cbdd.70393","DOIUrl":"10.1111/cbdd.70393","url":null,"abstract":"<p>Breast cancer is known as a frequently diagnosed malignancy in women. Over 70% of cases express estrogen receptor α (ERα). The activation of ERα promotes tumor proliferation and progression. Furthermore, mutations in ERα lead to acquired resistance against standard endocrine therapies such as tamoxifen. The induced resistance posed a significant clinical challenge in metastatic breast cancer. In this study, research for identifying novel, naturally derived compounds to inhibit the Y537S-mutated ERα was conducted using in silico methods supported by an in vitro cytotoxicity screen. Molecular docking and molecular dynamics simulations served as the primary in silico screening strategies. The top 2% of candidates were filtered from a docking screen of the IBS natural library composed of over 15,000 chemicals. From this group, 11 compounds were purchased and tested using a cell-based cytotoxicity assay in MCF-7 before advancing to detailed simulations. Five candidates were then advanced to 150 ns MD simulations. A post-MD analysis followed, including MM-PBSA binding free energy calculations and principal component analysis (PCA). The phytochemical ibs-04156 was identified as the most promising overall candidate, predicted to maintain consistent stability across both the wild-type and Y537S-mutated ERα, while ibs-18821 demonstrated potent mutant-specific inhibition via an allosteric mechanism involving spatial deviations in distal helices H3 and H11. This result shows that mutated ERα can be potentially targeted by bioactive phytochemical scaffolds found through molecular modeling, presenting a potential therapeutic strategy for metastatic breast cancer resistant to therapies such as tamoxifen.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889688","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":"An ALKBH3 Inhibitor HUHS199 Suppresses Proliferation of Glioblastoma Cells by Targeting 1-Methyladenosine on GADD45A mRNA","authors":"Manami Yamada,&nbsp;Hiroaki Hase,&nbsp;Honoka Kitamura,&nbsp;Toshiya Morie,&nbsp;Shuntaro Aoi,&nbsp;Yuko Ueda,&nbsp;Kaori Kitae,&nbsp;Tatsuhiko Furukawa,&nbsp;Nayuta Higa,&nbsp;Ryosuke Hanaya,&nbsp;Kazutake Tsujikawa","doi":"10.1111/cbdd.70385","DOIUrl":"10.1111/cbdd.70385","url":null,"abstract":"<p>Glioblastoma (GBM) is a highly aggressive, poor-prognosis brain tumor classified as WHO grade IV, for which effective treatments remain limited. Although AlkB homolog 3 (ALKBH3), a demethylase for 1-methyladenosine (m1A) and 3-methylcytidine (m3C) in DNA and RNA, has been implicated in cancer cell proliferation, its functional role in GBM remains unclear. We aimed to characterize the role of ALKBH3 in GBM and develop and evaluate a patented ALKBH3 inhibitor, HUHS199, to identify its molecular targets and therapeutic potential. We found that ALKBH3 was highly expressed in clinical GBM specimens; its knockdown inhibited GBM cell proliferation. HUHS199 inhibited GBM cell proliferation in a dose-dependent manner, induced G1 phase cell cycle arrest, and increased m1A levels in RNA. Furthermore, RNA immunoprecipitation–microarray analysis using an anti-m1A antibody identified growth arrest and DNA-damage-inducible protein GADD45 alpha (GADD45A) mRNA as a target of ALKBH3-mediated demethylation. These findings suggest that ALKBH3 promotes GBM cell proliferation via m1A demethylation of <i>GADD45A</i> mRNA. Collectively, this study highlights the therapeutic potential of ALKBH3 inhibition and presents HUHS199 as a first-in-class candidate for GBM treatment.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877044","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":"Integrative Multi-Omics Analysis Identifies Thrombosis-Associated Molecular Features Linked to Germline Susceptibility and Immune Cell Communication in Gastric Cancer","authors":"Xiaogang Lu,&nbsp;Lin Sun,&nbsp;Fujun Jin,&nbsp;Biao Cheng,&nbsp;Ying Huang,&nbsp;Yuzhu Tang,&nbsp;Xiaolong Nie,&nbsp;Feng Gao","doi":"10.1111/cbdd.70386","DOIUrl":"10.1111/cbdd.70386","url":null,"abstract":"<p>Emerging evidence indicates that coagulation-related molecular programs are associated with thrombosis, tumor progression, and molecular dysregulation in gastric cancer (GC). However, thrombosis-associated molecular features in GC and their potential links to inherited susceptibility remain insufficiently understood. Integrated analyses of transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were performed to identify thrombosis-associated genes and establish a machine learning-based prognostic signature. Genome-wide association study (GWAS), expression quantitative trait loci (eQTL), transcriptome-wide association study (TWAS), and Mendelian randomization (MR) analyses were conducted to investigate susceptibility-associated transcriptional programs in GC. Functional assays were used to evaluate candidate genes associated with malignant phenotypes. Single-cell RNA sequencing (scRNA-seq) and cell–cell communication analyses were further performed to characterize cell-type-specific expression patterns and potential intercellular interactions. A total of 22 differentially expressed thrombosis-associated genes were identified, and a prognostic signature comprising 14 genes was established. The signature stratified patients into high- and low-risk groups and showed prognostic performance in both the training and validation cohorts. Integrative GWAS, eQTL, and TWAS analyses identified susceptibility-associated transcriptional programs that were positively correlated with the thrombosis-associated risk score. Silencing ACTN2 and CRYAB significantly reduced GC cell migration and invasion. scRNA-seq analysis revealed relatively high CRYAB expression in neutrophils, and CellChat analysis suggested potential neutrophil-B cell interactions involving COLLAGEN-related signaling. This integrative multi-omics study identified a thrombosis-associated molecular signature linked to prognosis and germline susceptibility-associated transcriptional programs in GC. ACTN2 and CRYAB may represent candidate genes associated with GC cell migration and invasion, while single-cell analysis suggested potential immune-related communication features.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876983","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":"Targeting PIKfyve: Chemical Biology and Drug Discovery Insights","authors":"Athavan Alias Anand Selvam,&nbsp;Anamika Sharma","doi":"10.1111/cbdd.70395","DOIUrl":"10.1111/cbdd.70395","url":null,"abstract":"<p>PIKfyve inhibitors have evolved from niche probes into powerful tools for studying endolysosomal biology. Although PIKfyve inhibition has revealed important roles in membrane trafficking, autophagy, viral entry, and cancer-cell vulnerability, clinical translation remains limited by a narrow therapeutic window because disruption of PI(3,5)P₂ homeostasis causes profound lysosomal dysfunction. Future progress will depend on tuneable or partial inhibitors, improved selectivity, and targeted delivery. PIKfyve therefore provides a useful model for balancing potency, precision, and safety in lipid kinase drug discovery.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877058","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":"Identification of New Anti-Trypanosoma brucei Leads: An Integrated CRK12-Guided Virtual Screen With Experimental Validation","authors":"Qin Li,&nbsp;Chenggong Fu,&nbsp;Jiayi Luo,&nbsp;Qianqian Zhang,&nbsp;Lingling Wang,&nbsp;Xiaomeng Liu,&nbsp;Jiayue Qiu,&nbsp;Xiaoqing Gong,&nbsp;Henry H. Y. Tong,&nbsp;Xiaojun Yao,&nbsp;Dehua Lai,&nbsp;Huanxiang Liu","doi":"10.1111/cbdd.70389","DOIUrl":"10.1111/cbdd.70389","url":null,"abstract":"<p>Human African trypanosomiasis (HAT), caused by <i>Trypanosoma brucei</i>, remains a neglected tropical disease with a critical shortage of therapeutic options, underscoring the need for new chemotypes. Cell division cycle-2-related kinase 12 (CRK12) has emerged as a genetically essential and chemically validated target in kinetoplastids, yet experimentally supported CRK12-targeting chemotypes against <i>T. brucei</i> remain limited, and no experimental CRK12 structure is available. Here, we developed an integrated computational-experimental screening workflow to accelerate CRK12-guided hit discovery, combining ligand-based prescreening, structure-based virtual screening, molecular dynamics (MD) refinement, and experimental validation. An 8.6-million-compound library was prescreened using MACCS fingerprint screening and complex-based pharmacophore screening, followed by staged docking and MD simulations to prioritize candidates for experimental testing. Notably, four of ten purchased compounds showed strong growth inhibition against <i>T. brucei</i> at 10 μM, with IC₅₀ values of 6.09, 1.47, 0.81, and 1.33 μM, demonstrating a promising hit rate for this data-limited target. Binding-mode analysis revealed a conserved hinge-anchoring interaction pattern in the ATP-binding pocket, providing a structural rationale for follow-up analogue design. Overall, this study identifies new chemical starting points for anti-<i>T. brucei</i> drug discovery and demonstrates the utility of an AlphaFold2-enabled CRK12-guided screening strategy for targets with limited structural and ligand data.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867571","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":"Investigation of the In Vitro and In Silico Anticancer Potential of Novel 4-Arylthiazole-Hydrazone Derivatives","authors":"Zeynep Zişan Demirci,&nbsp;Erol Akgün,&nbsp;Gülşen Akalın Çiftçi,&nbsp;Leyla Yurttaş","doi":"10.1111/cbdd.70387","DOIUrl":"10.1111/cbdd.70387","url":null,"abstract":"<p>The anticancer efficacy of 4-aryl-2-hydrazinothiazole derivatives, which combine a thiazole known for its wide range of medicinal applications and a hydrazide/hydrazone structure known for its unique biological properties, has been determined in numerous studies. In this study, novel 2-[4-[(2-(4-substituted thiazol-2-yl)hydrazono)methyl]phenoxy]acetic acid derivatives (<b>2a–l</b>) were synthesized and evaluated for their anticancer activity in MCF-7 breast cancer, A549 lung cancer, and L929 normal cell lines using cytotoxicity, apoptosis, and caspase-3 activation assays. The compounds were found to exhibit high cytotoxicity, particularly showing more selective and high-potential antiproliferative activity on the MCF-7 cell line. In apoptosis studies, compounds <b>2c</b>, <b>2d</b>, and <b>2h</b> caused programmed cell death in MCF-7 cells exceeding 24%, close to cisplatin. Among these compounds, the derivative <b>2c</b> containing 4-methoxyphenyl caused caspase-3 activation at a level similar to cisplatin. To conduct in silico studies of the compounds, molecular docking studies with the (4QTX) caspase-3 enzyme, molecular dynamics simulation for three compounds (<b>2d</b>, <b>2g</b> and <b>2l</b>), and Density Functional Theory (DFT) studies were performed. These studies have shown that the carboxylate groups in the compounds form strong and stable interactions with Arg64 and Arg207.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867612","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}