SAR and QSAR in Environmental Research最新文献_第5页

Towards eco-friendly and biodegradable pesticides: intelligent consensus modelling and read-across for predicting soil half-life. 迈向生态友好和可生物降解的农药：智能共识模型和预测土壤半衰期的解读。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-12-01 Epub Date: 2025-12-16 DOI: 10.1080/1062936X.2025.2592843

A Kumar, S Kar, P K Ojha

{"title":"Towards eco-friendly and biodegradable pesticides: intelligent consensus modelling and read-across for predicting soil half-life.","authors":"A Kumar, S Kar, P K Ojha","doi":"10.1080/1062936X.2025.2592843","DOIUrl":"10.1080/1062936X.2025.2592843","url":null,"abstract":"Pesticides are widely used in agriculture to enhance crop yield and protect against pests. However, their persistence in soil can lead to long-term environmental contamination and pose health risks to humans and other organisms through indirect exposure via the food chain. In this study, we used in silico approaches like Quantitative Structure-Activity Relationship (QSAR) modelling, Intelligent Consensus Prediction (ICP), and chemical read-across to predict the soil degradation half-lives of various pesticides. Models were established using 2D molecular descriptors, thoroughly validated with the help of training and test sets validation parameters, and conformed to OECD guidelines. The predictive models were applied to the Pesticide Properties Database (PPDB) to demonstrate their utility in screening untested and/or newly synthesized pesticides, considering the domain of applicability. Key structural features associated with degradation were identified, providing valuable insights for the design of biodegradable and environmentally safer pesticides. This work contributes to data gap-filling, regulatory risk assessment, and the prioritization of new or untested pesticides for environmental evaluation.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1117-1132"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763821","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 identification of potential PAK1 inhibitors for anti-cancer therapy: an e-pharmacophore guided virtual screening study. 用于抗癌治疗的潜在PAK1抑制剂的计算鉴定：一项电子药效团引导的虚拟筛选研究

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-12-01 Epub Date: 2025-12-19 DOI: 10.1080/1062936X.2025.2595472

M Muthuvairam Subbulakshmi, H Nagarajan, S Pandi, S Subramaniyan, T Berchmans, J Jeyaraman

{"title":"Computational identification of potential PAK1 inhibitors for anti-cancer therapy: an e-pharmacophore guided virtual screening study.","authors":"M Muthuvairam Subbulakshmi, H Nagarajan, S Pandi, S Subramaniyan, T Berchmans, J Jeyaraman","doi":"10.1080/1062936X.2025.2595472","DOIUrl":"10.1080/1062936X.2025.2595472","url":null,"abstract":"Cancer remains a major global health challenge, with approximately 18 million new cases reported annually. Existing evidence highlights the PAK1 protein as a critical regulator of cancer progression, making it a promising therapeutic target. The PAK1 protein complexed with dibenzodiazepine was fetched from the PDB with the identifier 4ZLO. The structure was preprocessed through preparation and exposed to pharmacophore hypotheses on the Schrödinger suite programme, indicating key features of RRH. A multi-tiered docking-based screening workflow from the libraries of ZINC and Enamine databases identified five potential bioactive compounds: ZINC952869440, ZINC952869442, ENAMINE558, ENAMINE6304, and ENAMINE8429. The docking and MM/GBSA scores ranked from -5.02 to -8.34 kcal/mol and -46.10 to -50.41 kcal/mol. Remarkably, none of these candidates violated the rules of five, and the Qikprop parameters complied with pharmacokinetic suitability. The DFT analysis revealed energy gap scores ranged from -0.182 to -0.225 eV, indicating favourable electronic properties and stability of the ligands. Furthermore, molecular dynamics (MD) and essential dynamics (ED) studies validated the structural stability of the complexes. The secondary structure analysis indicated stable retention of α-helices and β-strands throughout the simulation. Moreover, the computational investigation identified potential PAK1 inhibitors that warrant further experimental testing and therapeutic development.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1181-1208"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782338","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

Integrated theoretical and experimental analysis of 4-amino-N-methylphthalimide: structural, spectroscopic, and anti-breast cancer potential. 4-氨基- n -甲基邻苯二胺的综合理论和实验分析：结构、光谱和抗乳腺癌潜力。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-12-01 Epub Date: 2025-12-05 DOI: 10.1080/1062936X.2025.2592101

N Karthik, S Sumathi, S Jeyavijayan, S Lalitha, A Messaoudi

{"title":"Integrated theoretical and experimental analysis of 4-amino-N-methylphthalimide: structural, spectroscopic, and anti-breast cancer potential.","authors":"N Karthik, S Sumathi, S Jeyavijayan, S Lalitha, A Messaoudi","doi":"10.1080/1062936X.2025.2592101","DOIUrl":"10.1080/1062936X.2025.2592101","url":null,"abstract":"The structure of 4-Amino-N-methylphthalimide (4AMP) was investigated through spectroscopic techniques and quantum chemical calculations. Structural parameters were optimized using the DFT-B3LYP/6-311++G(d,p) method in both gas and DMSO phases. Experimental results from powder XRD and reported single crystal XRD showed excellent agreement. The experimental FT-IR and FT-Raman spectra correlated well with theoretical vibrational frequencies, and UV-Vis spectra comparisons further validated the computational findings. Molecular electrostatic potential (MEP), Mulliken and natural charges, and Fukui function analyses highlighted the reactive regions of 4AMP. Natural bond orbital (NBO) analysis revealed stabilization energies of bonding and antibonding orbitals. Hirshfeld surface and fingerprint analyses provided insights into intra and intermolecular interactions. Biological studies indicated that 4AMP exhibited the strongest binding affinity towards the PI3Kα (PIK3CA catalytic subunit) at -6.9 kcal/mol, suggesting significant therapeutic potential. Molecular dynamics simulations over 100 ns have been performed to assess the stability and dynamic behaviour of 4AMP. Cytotoxicity assays demonstrated potent activity against breast cancer cell lines, with IC50 values of 16.89 μg/mL (MCF-7) and 19.53 μg/mL (MDA-MB-231). These findings suggest that 4AMP possesses promising anticancer activity, combining favourable structural, spectroscopic, and biological characteristics, making it a potential candidate for targeted breast cancer therapy.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1133-1159"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678563","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

Amyloid unravelled: computational modelling of the TasA enzyme in stabilizing biofilms in Bacillus cereus and its inhibitory profiles using a drug repurposing approach. 淀粉样蛋白的分解：在蜡样芽孢杆菌中稳定生物膜的TasA酶的计算模型及其使用药物再利用方法的抑制谱。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-12-01 Epub Date: 2026-01-06 DOI: 10.1080/1062936X.2025.2598608

R Abhirami, C Selvaraj, S K Singh

{"title":"Amyloid unravelled: computational modelling of the TasA enzyme in stabilizing biofilms in Bacillus cereus and its inhibitory profiles using a drug repurposing approach.","authors":"R Abhirami, C Selvaraj, S K Singh","doi":"10.1080/1062936X.2025.2598608","DOIUrl":"https://doi.org/10.1080/1062936X.2025.2598608","url":null,"abstract":"Amyloid-like proteins (ALPs) are key components of bacterial biofilms, reinforcing the extracellular matrix and supporting cell adhesion. Biofilms contribute significantly to chronic infections, antimicrobial resistance (AMR), and persistent diseases, posing major clinical and environmental challenges. TasA, a primary amyloid protein in biofilms, is well-studied in Bacillus subtilis, but its role in Bacillus cereus remains poorly understood. This study aimed to explore TasA as a target for anti-biofilm intervention. Due to the lack of an experimentally resolved structure, the 3D conformation of B. cereus TasA was predicted using computational modelling and validated through biophysical analyses. A structure-based virtual screening of FDA-approved compounds was conducted to identify potential inhibitors of TasA. Top candidates were further evaluated through molecular docking and triplicate molecular dynamics simulations to assess binding interactions and structural effects. Deferoxamine mesylate emerged as a strong inhibitor, demonstrating high binding affinity and destabilizing the amyloid fibril structure of TasA. This ligand-induced disruption may impair biofilm integrity and reduce AMR. Overall, the study presents TasA as a novel target for biofilm disruption in B. cereus and supports drug repurposing strategies for managing biofilm-associated infections.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":"36 12","pages":"1233-1262"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912831","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

System of self-consistent models synergistic or antagonistic with correlation intensity index: a combined perusal using MAO-A inhibitors. 自洽模型系统与相关强度指数协同或拮抗：使用MAO-A抑制剂的联合阅读。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-12-01 Epub Date: 2026-01-06 DOI: 10.1080/1062936X.2025.2596824

Bhawna, A Kumar, V Singh, P Kumar, S Kumar

{"title":"System of self-consistent models synergistic or antagonistic with correlation intensity index: a combined perusal using MAO-A inhibitors.","authors":"Bhawna, A Kumar, V Singh, P Kumar, S Kumar","doi":"10.1080/1062936X.2025.2596824","DOIUrl":"https://doi.org/10.1080/1062936X.2025.2596824","url":null,"abstract":"Neurodegenerative disorders are considered as one of the leading causes of disability and mortality. Monoamine oxidases play a crucial role in their management. Despite many monoamine oxidase inhibitors in the market problems like hepatotoxicity, drug interactions, irreversibility and selectivity etc. present lacunas in the current therapy. Therefore, development of more effective monoamine oxidase inhibitors is required. In the present research, Monte Carlo method-based and OECD principles-guided models on 192 monoamine oxidase-A (MAO-A) inhibitors are reported using index of ideality of correlation (IIC) and correlation intensity index (CII). These two criteria are responsible for enhanced statistical characteristics values. The predictive potential of the prepared random models has been estimated through the system of self-consistence which resulted in similar statistical predictive quality of the created models using different splits of the available data. Five new molecules (M1-M5) were designed by incorporation of extracted structural attributes. The designed molecules were analysed via molecular docking study, and compound M1 showed maximum endpoint value (pIC50 = 5.5) and binding affinity (-9.5 kcal mol-1). The entire designed molecule exhibited better binding affinity and MAO-A inhibitory activity than the parent molecule. The calculated pIC50 is highly correlated with binding affinity showing correlation value of 0.9540.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":"36 12","pages":"1209-1231"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912846","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

Assessing the adsorption coefficient of diverse chemicals on polyethylene microplastics through a QSPR approach. 用QSPR法评价不同化学物质在聚乙烯微塑料上的吸附系数。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-11-01 Epub Date: 2025-11-19 DOI: 10.1080/1062936X.2025.2576800

S Vardar, M Türker Saçan

{"title":"Assessing the adsorption coefficient of diverse chemicals on polyethylene microplastics through a QSPR approach.","authors":"S Vardar, M Türker Saçan","doi":"10.1080/1062936X.2025.2576800","DOIUrl":"https://doi.org/10.1080/1062936X.2025.2576800","url":null,"abstract":"Research on chemical adsorption onto microplastics is increasingly important in environmental studies. However, many existing models rely on basic structural properties, LSER descriptors, or 2D descriptor pools, often lacking robust external validation and applicability domain (AD) assessments. We revisited two literature studies to recompile a larger adsorption coefficient dataset (log Kd) of diverse organic chemicals onto polyethylene microplastics in pure water, applying rigorous data screening to ensure a higher-quality dataset and remove inconsistencies. log Kd values of 61 external chemicals were predicted from a dataset of 47 chemicals, including persistent, mobile and toxic (PMT) chemicals in both sets thereby extending predictions to PMT/vPvM compounds with limited experimental data. An extensive 3D descriptor set provided deeper mechanistic insights than 2D or physicochemical descriptors. Inclusion of 3D descriptors from dual-phase (gas and aqueous) geometry optimizations also improved mechanistic interpretation compared to gas-phase optimizations in literature. Our findings highlight the importance of strict external validation and a well-defined AD, using diverse validation metrics that improve upon the revisited studies. Adsorption correlated positively with lipophilicity and 3D-MoRSE descriptors, and negatively with -OH groups, ionization potential, and polarity. Model predictions aligned well with literature-reported log Kd values.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":"36 11","pages":"971-992"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145550368","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-based search of natural product derived multi-target ligands for the management of Alzheimer's and Parkinson's disease using structure-based pharmacophore modelling, virtual screening, MD docking, free energy analysis, ADMET profiling and DFT studies. 利用基于结构的药团建模、虚拟筛选、MD对接、自由能分析、ADMET分析和DFT研究，对用于阿尔茨海默病和帕金森病管理的天然产物衍生的多靶点配体进行基于计算的搜索。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-11-01 Epub Date: 2025-11-19 DOI: 10.1080/1062936X.2025.2579695

N Chhabra, B W Matore, A Murmu, A Kumar, P Gawande, J Singh, P P Roy

{"title":"A computational-based search of natural product derived multi-target ligands for the management of Alzheimer's and Parkinson's disease using structure-based pharmacophore modelling, virtual screening, MD docking, free energy analysis, ADMET profiling and DFT studies.","authors":"N Chhabra, B W Matore, A Murmu, A Kumar, P Gawande, J Singh, P P Roy","doi":"10.1080/1062936X.2025.2579695","DOIUrl":"https://doi.org/10.1080/1062936X.2025.2579695","url":null,"abstract":"Neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD), represent major global health concerns due to multifactorial pathology and lack of effective therapeutics. A comprehensive multi-target (MT) computational strategy was applied to identify natural product-derived therapeutics against four critical targets of AD and PD: acetylcholinesterase (AChE), dopamine receptor D2, monoamine oxidase B (MAO-B) and cyclooxygenase-2 (COX-2). Structure-based pharmacophore models were constructed for each target, validated and employed to virtually screen 2,54,850 compounds from the COCONUT database, following rigorous ADME-based filtering. Compounds with an average pharmacophore fit score ≥0.6 were shortlisted, yielding 55 promising candidates. These were examined through molecular dynamics (MD) docking using the CDOCKER algorithm. Four hits (N1-N4) displayed superior binding affinities relative to reference drugs donepezil (DNP) and safinamide (SAF). Binding free energy calculations further substantiated their interaction stability. ADMET analysis predicted favourable pharmacokinetic properties, efficient blood-brain barrier penetration and non-toxic profiles, with compound N1 (CNP0388746.0) emerging as the most promising candidate. Additionally, density functional theory (DFT) studies provided insights into the electronic characteristics and reactivity of top hits. Overall, this integrated in silico approach emphasized the potential of natural scaffolds as sustainable multi-target-directed ligands (MTDLs) for AD and PD therapeutics.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":"36 11","pages":"993-1024"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145550403","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

Effects of Tween 80 on three enzymes' activity in ibuprofen degradation: an insight into molecular docking and MD simulations. Tween 80对布洛芬降解过程中三种酶活性的影响：分子对接和MD模拟的洞察。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-11-01 Epub Date: 2025-11-12 DOI: 10.1080/1062936X.2025.2584059

X Yao, L Chen, H Zhang, R Wang

{"title":"Effects of Tween 80 on three enzymes' activity in ibuprofen degradation: an insight into molecular docking and MD simulations.","authors":"X Yao, L Chen, H Zhang, R Wang","doi":"10.1080/1062936X.2025.2584059","DOIUrl":"10.1080/1062936X.2025.2584059","url":null,"abstract":"Ibuprofen (IBP) poses potential threats to human health and the environment. Lignin peroxidase (Lip), manganese peroxidase (Mnp), and laccase are considered as safe, friendly enzymes for biodegradation of IBP. However, surfactants like Tween 80 can alter the activity of these enzymes in IBP degradation, yet the underlying molecular details remain unclear. To study the influence of Tween 80 on the interaction between three enzymes, Lip, Mnp, laccase, and IBP, molecular docking and molecular dynamics (MD) simulations were conducted. The results of molecular docking results confirmed that IBP bound to residues around the active site of these three enzymes through hydrophobic interactions and hydrogen bonds. During MD simulations, Tween 80 gradually assemble into micelles that interacted with the enzyme surface. This might have altered the solvent environment and changed the interactions between these enzymes and IBP, thereby achieving more effective degradation of IBP. The results of binding free energy calculations further revealed that Tween 80 could promote the degradation of IBP by these three enzymes, while Lip has the best biodegradation effect on IBP. Our study can offer theoretical insights into the roles of Lip, Mnp, and laccase in the degradation of IBP.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1025-1040"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496609","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

Thiazole pharmacophore-based discovery of novel SGLT2 inhibitors using virtual screening, molecular docking, and molecular dynamics simulation for diabetic nephropathy. 基于噻唑药物团的新型SGLT2抑制剂的发现，利用虚拟筛选、分子对接和分子动力学模拟治疗糖尿病肾病。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-11-01 Epub Date: 2025-11-13 DOI: 10.1080/1062936X.2025.2584054

V Lone, P Khona, M J Umekar, U D Kabra

{"title":"Thiazole pharmacophore-based discovery of novel SGLT2 inhibitors using virtual screening, molecular docking, and molecular dynamics simulation for diabetic nephropathy.","authors":"V Lone, P Khona, M J Umekar, U D Kabra","doi":"10.1080/1062936X.2025.2584054","DOIUrl":"10.1080/1062936X.2025.2584054","url":null,"abstract":"Diabetic nephropathy (DN), a serious complication of chronic diabetes mellitus, remains a leading cause of end-stage renal disease (ESRD). Although therapies targeting the renin-angiotensin-aldosterone system (RAAS) exist, many patients still face progressive renal decline, highlighting the need for improved treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors offer both glycaemic and renal benefits, yet glycosidic inhibitors are associated with adverse effects such as genitourinary infections and euglycemic ketoacidosis. This has prompted interest in non-glycosidic scaffolds. Thiazole, a drug-like heterocycle, shows promise as a core for novel SGLT2 inhibitors. In this study, a ligand-based pharmacophore model (DDHRR_1) was developed using known thiazole-based inhibitors and applied to virtual screening of Drug Central and Enamine libraries. Four compounds olodaterol, nebivolol, Z56768840, and Z8314156464 were identified, with olodaterol showing the most stable interactions during a 100 ns molecular dynamics (MD) simulation. Based on structural insights, a novel compound, NC-1, was rationally designed. NC-1 demonstrated a high pharmacophore fitness score (1.64), favourable docking energy (-11.1 kcal/mol), and stable MD interactions. This integrated computational approach offers a valuable platform for discovering non-glycosidic SGLT2 inhibitors and supports further development of NC-1 for potential treatment of DN.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1081-1103"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145506714","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

Integrated machine learning-driven QSAR modelling and systems biology approach for the identification of potential SARS-CoV-2 3CLpro inhibitors. 集成机器学习驱动的QSAR建模和系统生物学方法，用于识别潜在的sars - cov - 23clpro抑制剂。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2025-11-01 Epub Date: 2025-11-19 DOI: 10.1080/1062936X.2025.2584058

A Manaithiya, R Bhowmik, R Ray, S Kumar, S Sharma, B Mathew, W Gong, A Aspatwar

{"title":"Integrated machine learning-driven QSAR modelling and systems biology approach for the identification of potential SARS-CoV-2 3CLpro inhibitors.","authors":"A Manaithiya, R Bhowmik, R Ray, S Kumar, S Sharma, B Mathew, W Gong, A Aspatwar","doi":"10.1080/1062936X.2025.2584058","DOIUrl":"https://doi.org/10.1080/1062936X.2025.2584058","url":null,"abstract":"SARS-CoV-2 3C-like protease (3CLpro) is an essential viral enzyme responsible for processing viral polyproteins and is a validated target for small-molecule therapeutic intervention. This study presents an integrative cheminformatics and systems biology framework to identify and evaluate potential 3CLpro inhibitors. A curated dataset of 919 compounds from the CHEMBL database was used to develop predictive QSAR models based on substructure fingerprints and 1D/2D molecular descriptors. The best-performing models achieved strong correlation coefficients (0.9736 for training and 0.7413 for testing), and key molecular features were identified using feature importance analysis. A web-based tool, 3CLpro-Pred was developed to enable rapid prediction of compound bioactivity. Molecular docking and dynamics simulations further validated QSAR findings by elucidating key atomic-level interactions at the protease active site. Top hit compounds were prioritized for systems-level analysis at the host-pathogen interface, where gene ontology and KEGG pathway enrichment revealed their potential to modulate key host signalling pathways. Critical regulatory genes, including TBK1, PIK3CA, IKBKB, GSK3B, and CASP3, were identified as major nodes linking compound action to antiviral and immune processes. This study delivers a combinatorial computational pipeline to accelerate the discovery of 3CLpro-targeted antivirals, providing mechanistic insights and a shortlist of candidates for future experimental validation.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":"36 11","pages":"1041-1079"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145550355","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