SAR and QSAR in Environmental Research最新文献

Discovery of novel 1,3,4-oxadiazole derivatives as anticancer agents targeting thymidine phosphorylase: pharmacophore modelling, virtual screening, molecular docking, ADMET and DFT analysis. 靶向胸苷磷酸化酶的新型1,3,4-恶二唑类抗癌药物的发现：药效团建模、虚拟筛选、分子对接、ADMET和DFT分析。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-05-01 Epub Date: 2025-06-06 DOI: 10.1080/1062936X.2025.2512385

A Murmu, B W Matore, P Banjare, P P Roy, J Singh

{"title":"Discovery of novel 1,3,4-oxadiazole derivatives as anticancer agents targeting thymidine phosphorylase: pharmacophore modelling, virtual screening, molecular docking, ADMET and DFT analysis.","authors":"A Murmu, B W Matore, P Banjare, P P Roy, J Singh","doi":"10.1080/1062936X.2025.2512385","DOIUrl":"10.1080/1062936X.2025.2512385","url":null,"abstract":"Thymidine phosphorylase (TP) is a key enzyme involved in angiogenesis, tumour growth and closely linked to cancer progression and metastasis. This study represents the first comprehensive 3D-QSAR pharmacophore-based approach to identifying potential 1,3,4-oxadiazole derivatives as targeted TPIs for anticancer therapy. A dataset of 76 analogues with an experimental IC50 values was used to develop pharmacophore models. The BEST conformation method identified an optimal model (Hypo 2), featuring HBA, HBD and RA as key activity determinants with strong statistical validation (r2 = 0.69, ΔCost = 77.41, Q2 = 0.68 and MAE = 0.23). A virtual screening of 12,353 drug-like 1,3,4-oxadiazole compounds from PubChem and ChEMBL yielded 329 potential TPIs (IC50 < 10 μM). MD Docking using CDOCKER (PDB ID: 1UOU) identified the top hits interacting with critical TP residues (Thr151, Gly152, Lys221, Ser217, Thr118). ADMET analysis confirmed their drug-likeness with no significant toxicity. ChEMBL2058305 exhibited the highest binding stability (-85.508 kcal/mol), the lowest HOMO-LUMO gap (0.066 ha), and superior TP affinity, highlighting its potential as a promising TP inhibitor for anticancer therapy. This first report with integration of pharmacophore modelling, virtual screening, MD Docking, ADMET, MMGBSA and DFT will be beneficial for the discovery of novel TPIs.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"393-419"},"PeriodicalIF":2.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235033","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 and molecular profiling of a large set of diverse compounds targeting PPARγ: from comprehensive cheminformatics approach to tool development. 一组针对PPARγ的不同化合物的结构见解和分子分析：从综合化学信息学方法到工具开发。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-05-01 Epub Date: 2025-06-10 DOI: 10.1080/1062936X.2025.2514061

S A Amin, G Chakraborty, R Tarafdar, L Sessa, I Das, S Piotto

{"title":"Structural insights and molecular profiling of a large set of diverse compounds targeting PPARγ: from comprehensive cheminformatics approach to tool development.","authors":"S A Amin, G Chakraborty, R Tarafdar, L Sessa, I Das, S Piotto","doi":"10.1080/1062936X.2025.2514061","DOIUrl":"10.1080/1062936X.2025.2514061","url":null,"abstract":"This study integrates a robust cheminformatics approach (including chemical space exploration, Bayesian model-based fingerprint analysis, and cluster-driven molecular profiling) to reveal the key structural features influencing peroxisome proliferator activated receptor-gamma (PPARγ) modulatory activity. The Bayesian classification model effectively differentiates between the beneficial and adverse structural characteristics of PPARγ modulators. Structural motifs such as substituted benzylamine, phenoxyphenyl groups, 5-phenyl-1,3-thiazolidine scaffolds, and indole rings have been identified as positive contributors, enhancing PPARγ activity. Conversely, features like substituted tertiary amines and sulphonamide groups were found to have detrimental effects, suggesting that these should be deprioritized in the design of future PPARγ modulators. Additionally, molecular clustering provided a means to categorize structurally similar compounds, facilitating scaffold analysis, diversity calculation, and lead optimization for PPARγ modulators. To extend these findings to the broader scientific community, we have developed an open-access online tool, 'Fasda_v1.0', (https://fasdav1web.streamlit.app/) designed for cluster-driven molecular profiling of any dataset, enabling further exploration and application of these methods. This study offers valuable guidance for designing and developing novel therapeutics targeting PPARγ, thereby contributing to advancements in treating type 2 diabetes mellitus and related diseases.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"443-461"},"PeriodicalIF":2.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258844","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

First report on retention time prediction of pesticides and veterinary drugs in cow milk using read-across and intelligent consensus prediction: an alternative for hazard assessment employing food-informatics. 首次报道了使用读取和智能共识预测来预测牛奶中农药和兽药的保留时间：一种利用食品信息学进行危害评估的替代方法。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-05-01 Epub Date: 2025-06-17 DOI: 10.1080/1062936X.2025.2512387

A Kumar, P K Ojha

{"title":"First report on retention time prediction of pesticides and veterinary drugs in cow milk using read-across and intelligent consensus prediction: an alternative for hazard assessment employing food-informatics.","authors":"A Kumar, P K Ojha","doi":"10.1080/1062936X.2025.2512387","DOIUrl":"https://doi.org/10.1080/1062936X.2025.2512387","url":null,"abstract":"Milk is one of the primary sources of food. Pesticides and veterinary drugs are reaching directly or indirectly (pesticides containing grass or other cattle foods) into the milk of the cattle, which are serious health concerns to the animals, infants, babies, and humans. So, in-silico approaches like QSPR, read-across, etc., are used as an alternative (reduce time, cost, complex analytical process) for calculating retention time (RT). The present work involves the development of the first multiple PLS-based QSAR models for the estimation of RT of pesticides, veterinary drugs, and related chemical hazards in milk by strictly obeying the OECD principles. Based on the results, the quality of the models is good enough. In the current work, it was observed that lipophilicity, binding property, rotatable bonds, and reactivity are responsible for high RT while hydrophilicity, the presence of primary amines, aqueous solubility, and branching reduce the RT of the compounds. The established models were utilized to screen the PPDB database to justify its real-world application. The present study will be vital in the food-informatics area for the RT data-gap filling and identification of hazardous chemicals in milk. Thus, it will be helpful to maintain a healthier, safer, and eco-friendly ecosystem.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":"36 5","pages":"421-441"},"PeriodicalIF":2.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310341","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

High performance, large chemical coverage or both: DanishQSAR and hierarchies of post-hoc ensemble models optimized for sensitivity, specificity or balanced accuracy. 高性能，大化学覆盖或两者兼有：DanishQSAR和专为灵敏度，特异性或平衡精度优化的事后集成模型的层次结构。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-05-01 Epub Date: 2025-06-04 DOI: 10.1080/1062936X.2025.2510964

N G Nikolov, E B Wedebye

{"title":"High performance, large chemical coverage or both: DanishQSAR and hierarchies of post-hoc ensemble models optimized for sensitivity, specificity or balanced accuracy.","authors":"N G Nikolov, E B Wedebye","doi":"10.1080/1062936X.2025.2510964","DOIUrl":"10.1080/1062936X.2025.2510964","url":null,"abstract":"The trade-off between applicability domain size and prediction accuracy is a well-known phenomenon in QSAR. We have developed a modelling approach where multiple models with different applicability domain sizes and with different prediction accuracy are selected instead of a single best model. This approach is implemented in DanishQSAR, a new software for binary classification QSAR modelling, integrating descriptor calculation, descriptor selection, model development, validation and application. The various methods and options available in the software are automatically tested and efficiently combined during model development using a version of cross-validation-based grid search and post-hoc ensemble modelling. The resulting large and diverse pool of model candidates is then analysed to generate three hierarchies of models, optimized for sensitivity, specificity or balanced accuracy, respectively, for minimum to maximum coverage levels. When predicting a query compound, the system provides predictions from all models in the three hierarchies, at all coverage levels with user-defined steps, together with the individual model predictivity performances, producing a prediction profile rather than one prediction from a single model. Twenty data sets from the Danish (Q)SAR Database (https://qsar.food.dtu.dk) are used to demonstrate the performance. The developed binary classification models are highly accurate by cross- and external validation.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"365-391"},"PeriodicalIF":2.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216797","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

A computational perception of BBOX1-IP3R3 interaction uncovers inhibitors for dysregulated calcium signalling in triple negative breast cancer. BBOX1-IP3R3相互作用的计算感知揭示了三阴性乳腺癌中钙信号失调的抑制剂。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-04-01 Epub Date: 2025-05-14 DOI: 10.1080/1062936X.2025.2497380

P Sangavi, G R Shri, S K Singh, K Langeswaran

{"title":"A computational perception of BBOX1-IP3R3 interaction uncovers inhibitors for dysregulated calcium signalling in triple negative breast cancer.","authors":"P Sangavi, G R Shri, S K Singh, K Langeswaran","doi":"10.1080/1062936X.2025.2497380","DOIUrl":"10.1080/1062936X.2025.2497380","url":null,"abstract":"Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer unveiling negative expression on oestrogen receptors, progesterone receptors, and HER2. The anomalous activation of signalling pathways and specific types of mutations characterize the progression of TNBC. Protein-protein interaction in the tumour microenvironment plays a crucial role in tumour aggressiveness. Disrupting the signalling pathways that promote cell progression, migration, and survival opens up a promising avenue for targeting the aggressive form of TNBC. The present study emphasizes the molecular interaction mechanism driving the aggressive and recalcitrant TNBC between BBOX1-IP3R3. The BBOX1-IP3R3 complex destabilization was accomplished using compounds obtained from various databases through virtual screening, molecular, and essential dynamics. The interaction study revealed that the four hits bound at the interface and facilitated better binding affinity with the highest docking score and optimal binding free energy. In addition, the molecular dynamics simulation, PCA/FEL, and MM/PBSA analysis conclusively evaluate the binding potential of the compounds and unequivocally stabilize specific conformations or deception of the complexes in high-energy states. Thus, the identified compounds lead to the disruption of BBOX1-IP3R3 interaction, which aids in the therapeutic option of TNBC.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"305-332"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992722","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 design of benzothiazole and phthalimide-derived hybrids as protoporphyrinogen IX oxidase inhibitors. 苯并噻唑和邻苯二胺衍生物杂合体作为原卟啉原IX氧化酶抑制剂的硅晶设计。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-04-01 Epub Date: 2025-05-06 DOI: 10.1080/1062936X.2025.2496156

A C de Faria, A P L de Mesquita, E F F da Cunha, M P Freitas

{"title":"In silico design of benzothiazole and phthalimide-derived hybrids as protoporphyrinogen IX oxidase inhibitors.","authors":"A C de Faria, A P L de Mesquita, E F F da Cunha, M P Freitas","doi":"10.1080/1062936X.2025.2496156","DOIUrl":"10.1080/1062936X.2025.2496156","url":null,"abstract":"Protoporphyrinogen IX oxidase (PPO) inhibition is a critical strategy for weed control in crop production. This study employed a computational approach integrating QSAR modelling, docking studies, and molecular dynamics to investigate the inhibitory activities of benzothiazole- and phthalimide-derived compounds against PPO. The MIA-QSAR method modelled pKi values for 52 compounds, complemented by docking and molecular dynamics to analyse ligand-enzyme interactions and identify potential agrochemical candidates. QSAR analysis yielded predictive models with r2 = 0.77, q2 = 0.55, and r2 = 0.74. MIA plots guided the design of 12 derivatives, 5 of which showed promising pKi values (7.31-8.69). Docking and molecular dynamics revealed strong binding affinity and stability for these candidates. The presence of fluorine substituents and C=O and C=S bonds in tetrahydroisoindole moieties enhanced biological activity, leading to the proposition of effective PPO inhibitors. Synthetic routes for the top candidates were outlined for future development, aiming to improve agrochemical efficacy and address resistance issues in crop protection.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"287-303"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993943","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

Targeting drug-resistant Mycobacterium tuberculosis: an integrated computational approach to identify DprE2 inhibitors. 靶向耐药结核分枝杆菌：识别DprE2抑制剂的综合计算方法。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-04-01 Epub Date: 2025-05-29 DOI: 10.1080/1062936X.2025.2506055

S Saxena, A Banerjee, L Guruprasad

{"title":"Targeting drug-resistant Mycobacterium tuberculosis: an integrated computational approach to identify DprE2 inhibitors.","authors":"S Saxena, A Banerjee, L Guruprasad","doi":"10.1080/1062936X.2025.2506055","DOIUrl":"https://doi.org/10.1080/1062936X.2025.2506055","url":null,"abstract":"Mycobacterium tuberculosis remains one of the leading causes of death from a single infectious agent, posing a major global health challenge. The rise of drug-resistant strains has intensified the need for novel therapeutic agents. Pretomanid and delamanid, two recently developed antitubercular drugs, are bicyclic nitroimidazoles that act as prodrugs, requiring activation by specific mycobacterial enzymes. However, the precise molecular targets of their active metabolites are not fully explained. Recent studies have identified DprE2, an essential enzyme in the biosynthesis of decaprenylphosphoryl-β-D-arabinofuranose (DPA) and arabinogalactan, as a potential target of delamanid. In this study, we applied structure-based pharmacophore modelling to identify potential inhibitors targeting DprE2. High-throughput virtual screening, followed by molecular docking, was used to evaluate binding affinities. ADMET predictions were incorporated to assess drug likeness and pharmacokinetic profiles. Nine promising hits were shortlisted, and their binding stability was further evaluated using 250 ns molecular dynamics simulations. Binding free energy calculations using the MM-GBSA method were then applied to refine the selection, identifying five potent lead molecules. These candidates show strong potential for further development as DprE2 inhibitors, offering a new path in the fight against drug-resistant tuberculosis.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":"36 4","pages":"333-363"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174727","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

Identification, experimental validation, and computational evaluation of potential ALK inhibitors through hierarchical virtual screening. 鉴定，实验验证，并通过分层虚拟筛选潜在的ALK抑制剂的计算评估。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-04-01 Epub Date: 2025-04-29 DOI: 10.1080/1062936X.2025.2496155

Y K Zhang, J B Tong, M X Luo, J Y Zhao, Y L Yang, Y Sun, Z P Qing

{"title":"Identification, experimental validation, and computational evaluation of potential ALK inhibitors through hierarchical virtual screening.","authors":"Y K Zhang, J B Tong, M X Luo, J Y Zhao, Y L Yang, Y Sun, Z P Qing","doi":"10.1080/1062936X.2025.2496155","DOIUrl":"10.1080/1062936X.2025.2496155","url":null,"abstract":"Anaplastic Lymphoma Kinase (ALK) plays a pivotal oncogenic role in the onset and progression of malignancies such as non-small cell lung cancer, lymphoma, and neuroblastoma. ALK gene mutations or rearrangements significantly enhance tumour cell proliferation and survival. However, the emergence of resistance to existing ALK inhibitors in clinical settings remains a major challenge. Consequently, the development of next-generation inhibitors targeting ALK-resistant mutations has become a central focus in the field of anticancer drug discovery. In this study, a hierarchical virtual screening strategy based on protein structure was utilized to screen 87,454 ligand conformations from 50,000 compounds in the Topscience drug-like database. Structural clustering analysis and ADMET drug-likeness predictions led to the identification of two potential ALK inhibitors, F6524-1593 and F2815-0802. Subsequent activity validation, molecular docking, and molecular dynamics simulations elucidated their potential binding modes and mechanisms of action. This study provides valuable theoretical insights for the development of novel ALK inhibitors targeting drug-resistant mutations and offers guidance for optimizing ALK-targeted therapeutic strategies.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"271-285"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978040","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

Computational design of PARP-1 inhibitors: QSAR, molecular docking, virtual screening, ADMET, and molecular dynamics simulations for targeted drug development. PARP-1抑制剂的计算设计：QSAR、分子对接、虚拟筛选、ADMET和靶向药物开发的分子动力学模拟。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-03-01 Epub Date: 2025-04-28 DOI: 10.1080/1062936X.2025.2480859

N Najafi, M H Fatemi

{"title":"Computational design of PARP-1 inhibitors: QSAR, molecular docking, virtual screening, ADMET, and molecular dynamics simulations for targeted drug development.","authors":"N Najafi, M H Fatemi","doi":"10.1080/1062936X.2025.2480859","DOIUrl":"https://doi.org/10.1080/1062936X.2025.2480859","url":null,"abstract":"Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors have shown promise in treating various cancers with homologous recombination repair deficiencies, particularly in breast and ovarian cancers harbouring BRCA1/2 mutations. This study aimed to identify and optimize novel PARP-1 inhibitors using the phthalazinone scaffold, known for forming strong and selective interactions with the active site of PARP-1. Through a combination of Quantitative Structure-Activity Relationship (QSAR) modelling, molecular docking simulations, and virtual screening, we discovered compounds with significant anticancer potential. Both the Multiple Linear Regression (MLR) and Support Vector Machines (SVM) models, utilizing four selected molecular descriptors, demonstrated high predictive efficiency for inhibitory activity (MLR: r2 = 0.944, Q2cv (cross-validated correlation coefficient) = 0.921, root mean square error (RMSE) = 0.249; SVM: r2 = 0.947, Q2cv = 0.887, RMSE = 0.245). Molecular docking studies revealed that several new compounds exhibited strong interactions with key amino acids GLY 227A, MET 229A, PHE 230A, and TYR 246A within the PARP-1 active site, similar to those observed in reference inhibitors Olaparib and AZD2461. Then, the top-ranked compound's (3a) ligand-protein complex underwent a 200 ns molecular dynamics (MD) simulation, confirming stable binding and revealing a robust set of intermolecular interactions maintained under physiological conditions.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":"36 3","pages":"205-246"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994123","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

Identification of potential inhibitors of hypoxanthine-guanine phosphoribosyl transferase for cancer treatment by molecular docking, dynamics simulation and in vitro studies. 通过分子对接、动力学模拟和体外研究确定治疗癌症的次黄嘌呤-鸟嘌呤磷酸核糖基转移酶潜在抑制剂。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-03-01 Epub Date: 2025-03-24 DOI: 10.1080/1062936X.2025.2478500

O Afzal, A Altharawi, M A Alamri

{"title":"Identification of potential inhibitors of hypoxanthine-guanine phosphoribosyl transferase for cancer treatment by molecular docking, dynamics simulation and in vitro studies.","authors":"O Afzal, A Altharawi, M A Alamri","doi":"10.1080/1062936X.2025.2478500","DOIUrl":"10.1080/1062936X.2025.2478500","url":null,"abstract":"Hypoxanthine guanine phosphoribosyltransferase 1 (HPRT1) is a mutational biomarker and a housekeeping human reporter gene that is predominantly employed to assess mutation frequencies associated with cancer development. In this study, our purpose was to identify potential inhibitors against the human hypoxanthine guanine phosphoribosyltransferase (HPRT) protein encoded by HPRT1 gene by employing an integrated in silico approach. The library of 17,967 phytochemicals (IMPPAT 2.0 database) was screened for drug-like properties followed by molecular docking, resulting in the selection of top 20 phytochemicals. Further interaction profile revealed that IMPHY008718 (Gibberellin A34) and IMPHY011650 (Chasmanthin) binds at the GMP binding site of the HPRT1 protein. ADMET properties and biological function predictions of the selected compounds indicate their anticancer potential. Both IMPHY008718 and IMPHY011650 docked complexes were examined in 200 ns MD simulations. Comprehensive MD trajectory analysis was performed in addition to principal component, free energy and MM/PBSA analysis. Furthermore, in vitro human HPRT inhibition assay confirmed and revealed inhibitory potential for Gibberellin A34 (Ki 0.121 µM) and Chasmanthin (Ki 0.368 µM), as compared to standard inhibitor, HGPRT/TBrHGPRT1-IN-1 (Ki 0.032 µM). Overall, these results strongly recommend further experimental work concerning these plant-based molecules as human HPRT inhibitors for anticancer drug development.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"169-188"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692913","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