SAR and QSAR in Environmental Research最新文献

Integrated computational and experimental identification of Aurora A kinase inhibitors for breast cancer therapy. Aurora A激酶抑制剂用于乳腺癌治疗的综合计算和实验鉴定。

IF 2.8 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2026-10-19 DOI: 10.1080/1062936X.2026.2746034

J Singh, S Mishra, I Irfan, S A Amin, E Verma

{"title":"Integrated computational and experimental identification of Aurora A kinase inhibitors for breast cancer therapy.","authors":"J Singh, S Mishra, I Irfan, S A Amin, E Verma","doi":"10.1080/1062936X.2026.2746034","DOIUrl":"https://doi.org/10.1080/1062936X.2026.2746034","url":null,"abstract":"The present study aimed to identify potential Aurora A kinase (AURKA) inhibitors using an integrated computational and experimental approach. A total of 281 curated AURKA inhibitors from the ChEMBL database, with IC50 ≤ 1 nM, were analysed using physicochemical descriptors and clustering techniques, with K-means showing the best performance (0.504). The compounds were grouped into three clusters and used to generate a pharmacophore model. Hydrogen-bond acceptors, donors, hydrophobicity, and aromatic rings were identified as key pharmacophoric features. Among the generated models, ADDRR and AAADR exhibited the best PhaseHypoScore and ROC values. These validated models screened approximately 800 FDA-approved drugs from the ZINC database. Molecular docking found that rucaparib (ZINC000000025958; C1), riboflavin (ZINC000002036848; C2), and imiquimod (ZINC000019632912; C3) were effective AURKA inhibitors. Molecular dynamics (MD) simulations and MM-GBSA analysis indicated that the C1 protein-ligand complex maintained structural integrity and favourable binding energetics throughout the simulation trajectory. Further, in vitro MTT assays demonstrated significant dose-dependent anticancer activity and reduced AURKA expression in MCF-7 cells, highlighting rucaparib's potential for breast cancer therapy.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-19"},"PeriodicalIF":2.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In silico drug repurposing of beta-blockers against HSV-1 TK using molecular docking and molecular dynamics simulations. 基于分子对接和分子动力学模拟的-受体阻滞剂对HSV-1 TK的硅药物再利用。

IF 2.8 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2026-10-19 DOI: 10.1080/1062936X.2026.2746042

Ş Mollahüseyinoğlu, C Inan

{"title":"In silico drug repurposing of beta-blockers against HSV-1 TK using molecular docking and molecular dynamics simulations.","authors":"Ş Mollahüseyinoğlu, C Inan","doi":"10.1080/1062936X.2026.2746042","DOIUrl":"https://doi.org/10.1080/1062936X.2026.2746042","url":null,"abstract":"Herpes simplex virus type 1 (HSV-1) is highly prevalent, but emerging drug-resistant strains against nucleoside analogs like acyclovir demand novel therapeutics. This study employed an in silico drug repurposing approach to screen 41 beta-blockers as potential non-nucleoside inhibitors targeting HSV-1 thymidine kinase (TK). Molecular docking, 100 ns molecular dynamics (MD) simulations, MM/GBSA binding free energy calculations, per-residue energy decomposition, and ADMET analysis were performed. Docking results revealed several beta-blockers surpassed acyclovir (-5.20 kcal/mol) in binding energy, with bopindolol emerging as the top candidate (-9.32 kcal/mol). Interaction analysis showed bopindolol forms stable hydrogen bonds with Gln125, Arg163, and Arg222, alongside stabilizing hydrophobic interactions. MD simulations confirmed the structural stability of the bopindolol-HSV-1 TK complex, evidenced by stable RMSD, low residue fluctuations, persistent hydrogen bonding, and consistent protein compactness. MM/GBSA calculations yielded a favourable delta G binding of -53.08 ± 3.57 kcal/mol. Energy decomposition indicated binding is driven by van der Waals and electrostatic interactions, with key contributions from Arg222, Tyr172, Met128, and Gln125. Furthermore, ADMET analysis demonstrated favourable pharmacokinetic properties for bopindolol. Overall, bopindolol represents a promising non-nucleoside inhibitor scaffold targeting HSV-1 TK, warranting further experimental validation.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-22"},"PeriodicalIF":2.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HDAC8 Assistant: a QSAR-guided molecular generation platform for de novo design and virtual screening of HDAC8 inhibitors. HDAC8 Assistant：一个qsar引导的分子生成平台，用于HDAC8抑制剂的从头设计和虚拟筛选。

IF 2.8 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2026-10-16 DOI: 10.1080/1062936X.2026.2741359

O V Tinkov, V Y Grigorev

{"title":"HDAC8 Assistant: a QSAR-guided molecular generation platform for de novo design and virtual screening of HDAC8 inhibitors.","authors":"O V Tinkov, V Y Grigorev","doi":"10.1080/1062936X.2026.2741359","DOIUrl":"https://doi.org/10.1080/1062936X.2026.2741359","url":null,"abstract":"Histone deacetylase 8 (HDAC8) inhibitors are considered promising therapeutic agents for the treatment of cancer and several other diseases. In this study, regression QSAR models for HDAC8 inhibitors were developed using various types of molecular descriptors and machine learning algorithms. The best-performing weighted consensus model achieved an external predictive performance of Q2test = 0.62 for the complete test set and 0.71 for compounds within the applicability domain, covering 77% of the external data. Model reliability was confirmed by five-fold cross-validation and y-randomization tests. The developed QSAR model was integrated into the HDAC8 Assistant web application (https://hdac8-assistant.streamlit.app/), which includes a de novo molecular generation module based on recurrent neural networks (SMILES-RNN) and reinforcement learning (REINVENT 2). For targeted discovery of novel inhibitors, an original reward function was proposed that combines QSAR-predicted activity with applicability domain control for generated compounds. This approach enables simultaneous optimization of predicted inhibitory activity while limiting extrapolation beyond the model applicability domain. HDAC8 Assistant also implements assessment of drug-likeness according to the Muegge criteria, as well as PAINS, toxicophore, and Brenk structural-alert detection. Molecular docking was performed for the most promising compounds generated by HDAC8 Assistant to analyse their interactions with the HDAC8 active site.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-36"},"PeriodicalIF":2.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Machine learning and network pharmacology-assisted discovery of natural product inhibitors targeting Plasmodium falciparum lysyl-tRNA synthetase. 机器学习和网络药理学辅助发现针对恶性疟原虫赖氨酸- trna合成酶的天然产物抑制剂。

IF 2.8 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2026-10-15 DOI: 10.1080/1062936X.2026.2743104

P Alam, A Akhtar, Z Hasan, M Serajuddin, O Basudan, S Ahmed

{"title":"Machine learning and network pharmacology-assisted discovery of natural product inhibitors targeting Plasmodium falciparum lysyl-tRNA synthetase.","authors":"P Alam, A Akhtar, Z Hasan, M Serajuddin, O Basudan, S Ahmed","doi":"10.1080/1062936X.2026.2743104","DOIUrl":"https://doi.org/10.1080/1062936X.2026.2743104","url":null,"abstract":"The emergence of drug-resistant Plasmodium falciparum necessitates novel antimalarial strategies. Lysyl-tRNA synthetase from Plasmodium falciparum (PfLysRS), an essential enzyme involved in protein biosynthesis, represents a promising molecular target for structure-based drug discovery and development of effective antimalarial agents. In this study, an integrated computational workflow identified three natural product-derived lead compounds, MolPort-001-742-110, MolPort-000-778-336, and MolPort-001-740-194, through structure-based virtual screening with favourable binding affinity and interaction profiles within the catalytic pocket. Density functional theory (DFT) optimized ligand geometries and characterized their electronic properties, while five independent 200 ns molecular dynamics (MD) simulations confirmed stable protein-ligand interactions. Molecular mechanics/generalized Born surface area (MM/GBSA) binding free energy calculations, principal component analysis (PCA), free energy landscape (FEL) mapping, and quantum mechanics/molecular mechanics (QM/MM) analyses further demonstrated energetically favourable binding and provided mechanistic insights into ligand stabilization. Machine learning predicted promising pIC50 values, supporting potential inhibitory activity against PfLysRS, whereas network pharmacology suggested modulation of multiple malaria-related targets and pathways associated with parasite survival, host responses, and disease progression. Overall, three promising natural product scaffolds were identified as potential PfLysRS inhibitors, providing a strong computational basis for biochemical, cellular, in vivo, and preclinical validation towards next-generation antimalarial development.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-35"},"PeriodicalIF":2.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the thymidine phosphorylase inhibitory potential of bis-Schiff derivatives bearing thiobarbituric acid: insights into in vitro and in silico approaches. 探索含有硫代巴比妥酸的双希夫衍生物的胸腺嘧啶磷酸化酶抑制潜力：对体外和计算机方法的见解。

IF 2.8 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2026-10-12 DOI: 10.1080/1062936X.2026.2724287

H A Al-Ghulikah, I Ahmad, B Tüzün, N Muhammad, A Alam, I Zghab, S H Altayeb, A A Elhenawy, M Khan

{"title":"Exploring the thymidine phosphorylase inhibitory potential of bis-Schiff derivatives bearing thiobarbituric acid: insights into in vitro and in silico approaches.","authors":"H A Al-Ghulikah, I Ahmad, B Tüzün, N Muhammad, A Alam, I Zghab, S H Altayeb, A A Elhenawy, M Khan","doi":"10.1080/1062936X.2026.2724287","DOIUrl":"https://doi.org/10.1080/1062936X.2026.2724287","url":null,"abstract":"Thymidine phosphorylase (TP) is overexpressed in many cancers, promoting metastasis, angiogenesis, and tumor growth, making it a promising therapeutic target for anticancer drug development. In this study, bis-Schiff bases of thiobarbituric acid (3a-3g) were screened for in vitro TP inhibitory activity. In the series, four compounds 3c, 3d, 3b, and 3e exhibited potent inhibition with IC50 values ranging from (IC50 = 2.16 ± 1.94 µM) to (IC50 = 12.27 ± 1.78 µM). Density functional theory (DFT) calculations revealed that nitro-substituted derivatives possess the smallest HOMO and LUMO gaps (2.53-2.59 eV) and highest softness values (0.103-0.113 eV-1), indicating enhanced electronic reactivity. Molecular docking against TP enzyme showed strong binding affinities, with compound 3f achieving favorable docking score (-8.96 kcal/mol). Normal Mode Analysis (NMA) provided dynamic insights into the binding mechanisms, revealing that 3f-4EAD harnesses the intrinsic breathing motion of TP, while 3d-4LHM engages a distal allosteric network. A quantitative structure-activity relationship (QSAR) model (R2 = 0.91) was developed correlating quantum chemical descriptors with biological activity. The ADME/T analysis predicted acceptable pharmacokinetic profiles for the most active compounds. These preliminary findings identify 3c, 3d, and 3f as lead compounds warranting further pharmacological evaluation as TP-targeted anticancer agents.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-28"},"PeriodicalIF":2.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure-based computational analysis of Tetrazoloquinoline-thiazolidinedione conjugates against bacterial and fungal targets. 基于结构的四唑喹啉-噻唑烷二酮偶联物抗细菌和真菌靶标的计算分析。

IF 2.8 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2026-10-12 DOI: 10.1080/1062936X.2026.2738621

A Sharma, J Kumar

{"title":"Structure-based computational analysis of Tetrazoloquinoline-thiazolidinedione conjugates against bacterial and fungal targets.","authors":"A Sharma, J Kumar","doi":"10.1080/1062936X.2026.2738621","DOIUrl":"https://doi.org/10.1080/1062936X.2026.2738621","url":null,"abstract":"Increasing resistance in bacterial and fungal pathogens to currently available antimicrobial agents highlights the need for the development of new antimicrobial agents. Recently, Tetrazoloquinoline and thiazolidinedione analogues have been considered interesting heterocyclic moieties due to their potential activity against microbial infections. This study focused on identifying novel Tetrazoloquinoline-thiazolidinedione conjugates as potent antibacterial and antifungal agents using computational tools, including molecular docking, DFT, molecular dynamics simulation, and in silico ADMET analysis. The molecular docking studies showed that the studied compounds have good binding affinities and interactions with the target proteins 4DUH (-10.6 to -9.8 kcal/mol) and 2AIB (-12.4 to -11.0 kcal/mol). Of all, the trifluoromethyl-substituted compounds AS-56 and AS-296 have a strong affinity. Furthermore, DFT analysis indicated the ideal structural properties, while 100 ns molecular dynamics simulation analysis was performed to follow the behaviour of the complexes formed between the ligands and the target proteins to evaluate their stability over time. The results indicate that AS-56 and AS-296 have a stable conformation and binding patterns in a stimulating environment of the protein-ligand complexes. ADME analysis predicted that the compounds (AS-56, AS-16, and AS-68) have good oral bioavailability and pharmacokinetics. The toxicity profile examination of the compounds predicted acceptable toxicity for these lead compounds.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-48"},"PeriodicalIF":2.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rational modification of olive derived 4-ethylguaiacol into a BBB-permeable acetylcholinesterase inhibitor via molecular docking, DFT, and molecular dynamics: a computational approach to alzheimer's drug discovery. 通过分子对接、DFT和分子动力学将橄榄衍生的4-乙基愈木酚合理修饰为可渗透血脑屏障的乙酰胆碱酯酶抑制剂：阿尔茨海默病药物发现的计算方法。

IF 2.8 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2026-10-09 DOI: 10.1080/1062936X.2026.2740626

A Aqeel, F Bashir, M Asad, A Asad, S Jafar, M Yasir

{"title":"Rational modification of olive derived 4-ethylguaiacol into a BBB-permeable acetylcholinesterase inhibitor via molecular docking, DFT, and molecular dynamics: a computational approach to alzheimer's drug discovery.","authors":"A Aqeel, F Bashir, M Asad, A Asad, S Jafar, M Yasir","doi":"10.1080/1062936X.2026.2740626","DOIUrl":"https://doi.org/10.1080/1062936X.2026.2740626","url":null,"abstract":"Alzheimer's disease (AD) affects more than 55 million people worldwide, yet no disease-modifying therapy has been approved. Here, 23 phytochemicals from Olea europaea (olive) were evaluated using a multi-filter pipeline comprising ADME/drug-likeness screening, BBB permeability assessment, molecular docking, DFT analysis, and MD simulations. This is the first computational study of olive phytochemicals targeting AChE to use BBB permeability as an explicit screening filter, addressing the CNS penetrance gap that limits translation of prior in silico hits. ADME screening (through SwissADME) identified three Lipinski-compliant, BBB-permeable candidates. Among these, 4-ethylguaiacol exhibited the strongest AChE binding (-7.0 kcal/mol) and a favorable HOMO-LUMO energy gap (6.09 eV), indicating moderate chemical reactivity and stability. Structure-guided optimization of 4-ethylguaiacol using RDKit led to the design of AM-11; 4-ethyl-5-(1-hydroxycyclopropyl)-2-methoxyphenol, whose C-5 hydroxycyclopropyl group forms direct hydrogen bond with catalytic residue, Ser203. AM-11 showed improved binding affinity (-7.9 kcal/mol), stable RMSD throughout a 100 ns MD simulation, and a predicted LD₅₀ of 720 mg/kg (Class IV), a better acute toxicity profile than donepezil (505 mg/kg). These findings position AM-11 as a as a computational lead for a BBB-permeable AChE inhibitor scaffold requiring experimental validation, and the pipeline as a reproducible framework for phytochemical-based lead optimization in AD.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-37"},"PeriodicalIF":2.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural insights into the binding potential of natural therapeutic leads as antiviral agents against human Metapneumovirus nucleoprotein. 天然治疗先导物作为抗病毒药物对抗人偏肺病毒核蛋白的结合潜力的结构见解。

IF 2.8 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2026-10-07 DOI: 10.1080/1062936X.2026.2734388

M Jayaraman, M Muthuvairam Subbulakshmi, S Nathar, D Prabhu, R Vijayarangan, J Jeyaraman

{"title":"Structural insights into the binding potential of natural therapeutic leads as antiviral agents against human Metapneumovirus nucleoprotein.","authors":"M Jayaraman, M Muthuvairam Subbulakshmi, S Nathar, D Prabhu, R Vijayarangan, J Jeyaraman","doi":"10.1080/1062936X.2026.2734388","DOIUrl":"https://doi.org/10.1080/1062936X.2026.2734388","url":null,"abstract":"Human metapneumovirus (hMPV), a member of the family Pneumoviridae and the genus Metapneumovirus, is a prevalent cause of respiratory tract infections, leading to severe complications and even death. As of now, there are no approved specific antiviral drugs or vaccines for hMPV, underscoring the need for potential therapeutic candidates. Hence, the present study employed a structure-based virtual screening (SBVS) of prepared ligands from CMNPD and SPECS databases against the hMPV nucleoprotein. Multi-level precision screening identified CMNPD3066, CMNPD12667, CMNPD25748, SPECS-AE-765, and SPECS-AP-123 as the top computationally prioritized compounds. These compounds demonstrated favourable predicted interactions with the docking scores ranging from -9.8 to -7.5 kcal/mol, and post-docking MMGBSA binding free energies ranging from -74.02 to -54.81 kcal/mol. Further, ADME/T evaluation predicted that these candidates were not involved in the violation of Lipinski's rule of five (Ro5) and all demonstrated favourable pharmacokinetic profiles. Subsequent 500 ns molecular dynamics simulations (MDS) and essential dynamics (ED) analyses, including principal component analysis (PCA) and free energy landscape (FEL) mapping, revealed the conformational stability of the nucleoprotein-ligand complexes throughout the simulation period. Collectively, the study concludes that the identified hit molecules are promising binding candidates for therapeutic development against hMPV and warrant further experimental and clinical validation.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-26"},"PeriodicalIF":2.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Network toxicology screening of plastic-associated chemicals reveals candidates with structural mimicry to Alzheimer's disease-relevant molecules and predicted neurotoxicity. 塑料相关化学物质的网络毒理学筛选揭示了与阿尔茨海默病相关分子具有结构模仿的候选物质和预测的神经毒性。

IF 2.8 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2026-07-01 Epub Date: 2026-07-09 DOI: 10.1080/1062936X.2026.2697791

W Cai, J Li, C Chen, J Mei, Y Liu

{"title":"Network toxicology screening of plastic-associated chemicals reveals candidates with structural mimicry to Alzheimer's disease-relevant molecules and predicted neurotoxicity.","authors":"W Cai, J Li, C Chen, J Mei, Y Liu","doi":"10.1080/1062936X.2026.2697791","DOIUrl":"10.1080/1062936X.2026.2697791","url":null,"abstract":"Alzheimer's disease (AD) pathogenesis involves environmental factors, with plastic-associated chemicals emerging as potential neurotoxicants. This study employed a computational toxicology framework to screen plastic-associated chemicals for potential interference with AD-related pathways. From a compiled library of 12,751 plastic-associated chemicals, 2,315 compounds with high blood-brain barrier (BBB) permeability were identified. Using Morgan fingerprints and Tanimoto similarity (threshold ≥ 0.6), we pinpointed chemicals structurally analogous to known AD-active molecules, including 3,5-Dimethoxystilbene (similarity 0.731 to a resveratrol derivative) and Isoeugenol (similarity 0.710 to isorhapontigenin). Structural similarity alone does not imply toxicity; therefore, we further evaluated these candidates using target prediction, molecular docking, and in silico toxicity profiling. Target prediction and molecular docking indicated that several compounds may interact with core AD-related targets (e.g. AChE, MAOB, APP). Notably, ProTox-3.0 profiling revealed that both 3,5-Dimethoxystilbene and Isoeugenol exhibit a potential dual profile of concern: high predicted BBB penetrance (probability > 0.7) and predicted potential for neurotoxic effects (probability 0.54-0.68), although these moderate probability scores warrant cautious interpretation. High-affinity binding was validated for 3,5-Dimethoxystilbene with AChE (-9.1 kcal/mol), comparable to known AChE inhibitors in our docking validation. This study prioritizes plastic-associated chemicals with a 'brain-penetrating and potentially neurotoxic' profile based on integrated computational evidence, providing a data-driven foundation for experimental validation.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"593-618"},"PeriodicalIF":2.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computer-aided drug design of quinoxaline based selective oestrogen receptor α modulators for breast cancer therapy: molecular docking, MD simulation, MM-PBSA and ADME/T analysis. 基于喹啉的选择性雌激素受体α调节剂用于乳腺癌治疗的计算机辅助药物设计：分子对接、MD模拟、MM-PBSA和ADME/T分析

IF 2.8 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2026-07-01 Epub Date: 2026-09-07 DOI: 10.1080/1062936X.2026.2719503

A Sharma, D Kumar, B Narasimhan, R K Marwaha

{"title":"Computer-aided drug design of quinoxaline based selective oestrogen receptor α modulators for breast cancer therapy: molecular docking, MD simulation, MM-PBSA and ADME/T analysis.","authors":"A Sharma, D Kumar, B Narasimhan, R K Marwaha","doi":"10.1080/1062936X.2026.2719503","DOIUrl":"10.1080/1062936X.2026.2719503","url":null,"abstract":"Oestrogen receptor alpha (ERα) is a driver of hormone-dependent breast cancer, yet current therapies are often hindered by drug resistance and adverse effects. In this study, we developed a structure-based virtual screening workflow to identify novel quinoxaline derivatives as computationally prioritized potential ERα modulators. The quinoxaline analogues obtained from PubChem are screened through validated docking model of ERα. The top-ranked candidates were further refined by MD simulations in GROMACS for 300 ns to assess complex stability and interaction persistence, followed by MM-PBSA binding free energy calculations to quantify binding energetics. The prioritized quinoxaline hits exhibited more favourable predicted docking scores than reference ligand, tamoxifen, while MD trajectory analyses indicated stable complex formation with sustained predicted interactions involving key ERα binding site residues. MM-PBSA highlights LIG3 as the most promising lead with a favourable energy (ΔG = -34.15 kcal/mol). Complementary ADMET profiling predicted favourable pharmacokinetic behaviour and low toxicity for the prioritized compounds. This integrated in silico strategy demonstrates that quinoxaline scaffolds, specifically LIG3, represent promising computationally prioritized templates for the further development and experimental evaluation of ERα targeted ligands. These findings provide a reliable computational framework for the prioritization and structural optimization of next-generation anti-breast cancer agents.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"655-678"},"PeriodicalIF":2.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0