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

Correction. 更正。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-02-01 Epub Date: 2024-02-06 DOI: 10.1080/1062936X.2024.2312758

引用次数: 0

Steroidal hydrazones as antimicrobial agents: biological evaluation and molecular docking studies. 作为抗菌剂的甾族酰肼：生物学评价和分子对接研究。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-02-01 Epub Date: 2024-02-05 DOI: 10.1080/1062936X.2024.2309183

M Merlani, N Nadaraia, N Barbakadze, L Amiranashvili, M Kakhabrishvili, A Petrou, T Carević, J Glamočlija, A Geronikaki

引用次数: 0

BC CLC-Pred: a freely available web-application for quantitative and qualitative predictions of substance cytotoxicity in relation to human breast cancer cell lines. BC CLC-Pred：免费提供的网络应用程序，用于定量和定性预测与人类乳腺癌细胞系有关的物质的细胞毒性。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-01-01 Epub Date: 2024-01-29 DOI: 10.1080/1062936X.2023.2289050

A A Lagunin, A S Sezganova, E S Muraviova, A V Rudik, D A Filimonov

{"title":"BC CLC-Pred: a freely available web-application for quantitative and qualitative predictions of substance cytotoxicity in relation to human breast cancer cell lines.","authors":"A A Lagunin, A S Sezganova, E S Muraviova, A V Rudik, D A Filimonov","doi":"10.1080/1062936X.2023.2289050","DOIUrl":"10.1080/1062936X.2023.2289050","url":null,"abstract":"In silico prediction of cell line cytotoxicity considerably decreases time and financial costs during drug development of new antineoplastic agents. (Q)SAR models for the prediction of drug-like compound cytotoxicity in relation to nine breast cancer cell lines (T47D, ZR-75-1, MX1, Hs-578T, MCF7-DOX, MCF7, Bcap37, MCF7R, BT-20) were created by GUSAR software based on the data from ChEMBL database (v. 30). The separate datasets related with IC50 and IG50 values were used for the creation of (Q)SAR models for each cell line. Based on leave-one-out and 5F CV procedures, 24 reasonable (Q)SAR models were selected for the creation of a freely available web-application (BC CLC-Pred: https://www.way2drug.com/bc/) to predict substance cytotoxicity in relation to human breast cancer cell lines. The mean accuracies of prediction r2, RMSE, Balance Accuracy for the selected (Q)SAR models calculated by 5F CV were 0.599, 0.679 and 0.875, respectively. As a result, BC CLC-Pred provides simultaneous quantitative and qualitative predictions of IC50 and IG50 values for most of the nine breast cancer cell lines, which may be helpful in selecting promising compounds and optimizing lead compounds during the development of new antineoplastic agents against breast cancer.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-9"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138809194","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

Descriptor generation from Morgan fingerprint using persistent homology. 利用持久同源性从摩根指纹中生成描述符。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-01-01 Epub Date: 2024-01-29 DOI: 10.1080/1062936X.2023.2301327

T Ehiro

{"title":"Descriptor generation from Morgan fingerprint using persistent homology.","authors":"T Ehiro","doi":"10.1080/1062936X.2023.2301327","DOIUrl":"10.1080/1062936X.2023.2301327","url":null,"abstract":"In cheminformatics, molecular fingerprints (FPs) are used in various tasks such as regression and classification. However, predictive models often underutilize Morgan FP for regression and related tasks in machine learning. This study introduced descriptors derived from reshaped Morgan FPs using persistent homology for the predictive accuracy improvement. In the solvation free energy (FreeSolv) and water solubility (ESOL) datasets, persistent homology was found to enhance predictive accuracy compared to the use of only Morgan FPs. Notably, using the first-order persistence diagram (PD1) for descriptor generation resulted in more significant improvements than using the zeroth-order persistence diagram (PD0). Combining 4096 bits Morgan FPs with PD1-generated descriptors increased the average coefficient of determination in the Gaussian process regression from 0.597 to 0.667 for FreeSolv and from 0.629 to 0.654 for ESOL. Adjusting the grid size parameter during PD-based descriptor generation is crucial, as finer grids, especially with PD0, generate more descriptors but reduce predictive accuracy. Coarsening the grid or applying principal component analysis (PCA) mitigates overfitting and enhances accuracy. When descriptors were generated from Morgan FPs with randomly shuffled bit positions, coarsening the grid and/or applying PCA achieved similar accuracy improvements as when the persistent homology of the original Morgan FPs was used.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"31-51"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484534","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

q-RASTR modelling for prediction of diverse toxic chemicals towards T. pyriformis. q-RASTR 模型用于预测各种有毒化学物质对吡咯并蚜的影响。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-01-01 Epub Date: 2024-01-29 DOI: 10.1080/1062936X.2023.2298452

V Ghosh, A Bhattacharjee, A Kumar, P K Ojha

{"title":"q-RASTR modelling for prediction of diverse toxic chemicals towards T. pyriformis.","authors":"V Ghosh, A Bhattacharjee, A Kumar, P K Ojha","doi":"10.1080/1062936X.2023.2298452","DOIUrl":"10.1080/1062936X.2023.2298452","url":null,"abstract":"A series of diverse organic compounds impose serious detrimental effects on the health of living organisms and the environment. Determination of the structural aspects of compounds that impart toxicity and evaluation of the same is crucial before public usage. The present study aims to determine the structural characteristics of compounds for Tetrahymena pyriformis toxicity using the q-RASTR (Quantitative Read Across Structure-Toxicity Relationship) model. It was developed using RASTR and 2-D descriptors for a dataset of 1792 compounds with defined endpoint (pIGC50) against a model organism, T. pyriformis. For the current study, the whole dataset was divided based on activity/property into the training and test sets, and the q-RASTR model was developed employing six descriptors (three latent variables) having r2, Q2F1 and Q2 values of 0.739, 0.767, and 0.735, respectively. The generated model was thoroughly validated using internationally recognized internal and external validation criteria to assess the model's dependability and predictability. It was highlighted that high molecular weight, aromatic hydroxyls, nitrogen, double bonds, and hydrophobicity increase the toxicity of organic compounds. The current study demonstrates the applicability of the RASTR algorithm in QSTR model development for the prediction of toxic chemicals (pIGC50) towards T. pyriformis.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"11-30"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404231","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

Ligand-based virtual screening and biological evaluation of inhibitors of Mycobacterium tuberculosis H37Rv. 基于配体的结核分枝杆菌 H37Rv 抑制剂的虚拟筛选和生物学评价。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-01-01 Epub Date: 2024-01-29 DOI: 10.1080/1062936X.2024.2304803

P V Pogodin, E G Salina, V V Semenov, M M Raihstat, D S Druzhilovskiy, D A Filimonov, V V Poroikov

{"title":"Ligand-based virtual screening and biological evaluation of inhibitors of Mycobacterium tuberculosis H37Rv.","authors":"P V Pogodin, E G Salina, V V Semenov, M M Raihstat, D S Druzhilovskiy, D A Filimonov, V V Poroikov","doi":"10.1080/1062936X.2024.2304803","DOIUrl":"10.1080/1062936X.2024.2304803","url":null,"abstract":"Novel antimycobacterial compounds are needed to expand the existing toolbox of therapeutic agents, which sometimes fail to be effective. In our study we extracted, filtered, and aggregated the diverse data on antimycobacterial activity of chemical compounds from the ChEMBL database version 24.1. These training sets were used to create the classification and regression models with PASS and GUSAR software. The IOC chemical library consisting of approximately 200,000 chemical compounds was screened using these (Q)SAR models to select novel compounds potentially having antimycobacterial activity. The QikProp tool (Schrödinger) was used to predict ADME properties and find compounds with acceptable ADME profiles. As a result, 20 chemical compounds were selected for further biological evaluation, of which 13 were the Schiff bases of isoniazid. To diversify the set of selected compounds we applied substructure filtering and selected an additional 10 compounds, none of which were Schiff bases of isoniazid. Thirty compounds selected using virtual screening were biologically evaluated in a REMA assay against the M. tuberculosis strain H37Rv. Twelve compounds demonstrated MIC below 20 µM (ranging from 2.17 to 16.67 µM) and 18 compounds demonstrated substantially higher MIC values. The discovered antimycobacterial agents represent different chemical classes.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":"35 1","pages":"53-69"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571119","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

Metrics for estimating vapour pressure deviation from ideality in binary mixtures. 估计二元混合物中蒸气压偏离理想状态的度量。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2023-11-20 DOI: 10.1080/1062936X.2023.2280634

A K D Celsie, J M Parnis, T N Brown

{"title":"Metrics for estimating vapour pressure deviation from ideality in binary mixtures.","authors":"A K D Celsie, J M Parnis, T N Brown","doi":"10.1080/1062936X.2023.2280634","DOIUrl":"https://doi.org/10.1080/1062936X.2023.2280634","url":null,"abstract":"A novel method is introduced for estimating the degree of interactions occurring between two different compounds in a binary mixture resulting in deviations from ideality as predicted by Raoult's law. Metrics of chemical similarity between binary mixture components were used as descriptors and correlated with the Root-Mean Square Error (RMSE) associated with Raoult's law calculations of total vapour pressure prediction, including Abraham descriptors, sigma moments, and several chemical properties. The best correlation was for a quantitative structure-activity relationship (QSAR) equation using differences in Abraham parameters as descriptors (r2 = 0.7585), followed by a QSAR using differences in COSMO-RS sigma moment descriptors (r2 = 0.7461), and third by a QSAR using differences in the chemical properties of log KAW, melting point, and molecular weight as descriptors (r2 = 0.6878). Of these chemical properties, Δlog KAW had the strongest correlation with deviation from Raoult's law (RMSE) and this property alone resulted in an r2 of 0.6630. These correlations are useful for assessing the expected deviation in Raoult's law estimations of vapour pressures, a key property for estimating inhalation exposure.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-19"},"PeriodicalIF":3.0,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138047802","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

Discovery of dual-target natural inhibitors of meprins α and β metalloproteases for inflammation regulation: pharmacophore modelling, molecular docking, ADME prediction, and molecular dynamics studies. meprins α和β金属蛋白酶炎症调节双靶点天然抑制剂的发现:药效团建模、分子对接、ADME预测和分子动力学研究。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2023-11-13 DOI: 10.1080/1062936X.2023.2277425

L Eltaib, A A Alzain

{"title":"Discovery of dual-target natural inhibitors of meprins α and β metalloproteases for inflammation regulation: pharmacophore modelling, molecular docking, ADME prediction, and molecular dynamics studies.","authors":"L Eltaib, A A Alzain","doi":"10.1080/1062936X.2023.2277425","DOIUrl":"https://doi.org/10.1080/1062936X.2023.2277425","url":null,"abstract":"Meprins, zinc-dependent metalloproteinases belonging to the metzincin family, have been associated with various inflammatory diseases due to their abnormal expression and activity. In this study, we utilized pharmacophore modelling to identify crucial features for discovering potential dual inhibitors targeting meprins α and β. We screened four pharmacophoric features against a library of 270,540 natural compounds from the Zinc database, resulting in 84,092 matching compounds. Molecular docking was then performed on these compounds, targeting the active sites of meprins α and β. Docking results revealed six compounds capable of interacting with both isoforms, with binding affinities ranging from -10.0 to -10.5 kcal/mol and -6.9 to -9.9 kcal/mol for meprin α and β, respectively. Among these compounds, ZINC000008790788 and ZINC000095099469 displayed superior docking scores and MM-GBSA binding free energy compared to reference ligands. Furthermore, these two compounds exhibited acceptable predicted pharmacokinetic properties and stable interactions with meprins α and β during molecular dynamics simulations. This study presents a comprehensive approach for identifying potential dual inhibitors of meprin α and β, offering insights into the development of therapeutic interventions for inflammatory diseases associated with meprin dysregulation.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-23"},"PeriodicalIF":3.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89719416","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

QSAR assessment of aquatic toxicity potential of diverse agrochemicals. 不同农用化学品水生毒性潜力的QSAR评估。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2023-11-09 DOI: 10.1080/1062936X.2023.2278074

A Nath, P K Ojha, K Roy

{"title":"QSAR assessment of aquatic toxicity potential of diverse agrochemicals.","authors":"A Nath, P K Ojha, K Roy","doi":"10.1080/1062936X.2023.2278074","DOIUrl":"https://doi.org/10.1080/1062936X.2023.2278074","url":null,"abstract":"The fast-increasing number of commercially produced chemicals challenges the experimental ecotoxicity assessment methods, which are costly, time-consuming, and dependent on the sacrifice of animals. In this regard, Quantitative Structure-Property/Activity Relationships (QSPR/QSAR) have led the way in developing ecotoxicity assessment models. In this study, QSAR models have been developed using the pEC50 values of 82 diverse agrochemicals or agro-molecules against a planktonic crustacean Daphnia magna with easily interpretable 2D descriptors. Moreover, a link among octanol-water partition coefficient (KOW), bio-concentration factor (BCF), and critical body residue (CBR) has been addressed, and their imputation for the prediction of the toxicity endpoint (EC50) has been done with an objective of the advanced exploration of several ecotoxicological parameters for toxic chemicals. The developed partial least squares (PLS) models were validated rigorously and proved to be robust, sound, and immensely well-predictive. The final Daphnia toxicity model derived from experimental derived properties along with computed descriptors emerged better in statistical quality and predictivity than those obtained solely from computed descriptors. Additionally, the pEC50 and other important properties (log KOW, log BCF, and log CBR) for a set of external agro-molecules, not employed in model development, were predicted to show the predictive ability of the models.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-20"},"PeriodicalIF":3.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71522495","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 molecular interactions of potential inhibitors against the spleen tyrosine kinase implicated in autoimmune disorders via virtual screening and molecular dynamics simulations. 通过虚拟筛选和分子动力学模拟，探索潜在抑制剂与自身免疫性疾病相关的脾脏酪氨酸激酶的分子相互作用。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2023-10-26 DOI: 10.1080/1062936X.2023.2266364

S Samanta, M F Sk, S Koirala, P Kar

{"title":"Exploring molecular interactions of potential inhibitors against the spleen tyrosine kinase implicated in autoimmune disorders via virtual screening and molecular dynamics simulations.","authors":"S Samanta, M F Sk, S Koirala, P Kar","doi":"10.1080/1062936X.2023.2266364","DOIUrl":"https://doi.org/10.1080/1062936X.2023.2266364","url":null,"abstract":"The spleen tyrosine kinase (Syk) plays a pivotal role in immune cells' signal transduction mechanism. While fostamatinib, an FDA-approved Syk inhibitor, is currently used to treat immune thrombocytopenia, the search for improved Syk-targeted medications to treat autoimmune diseases is still underway. Herein, we screened 38,493 compounds against Syk and selected eight leads based on the docking score and ADMET properties, and performed 3<math><mo>×</mo></math>200 ns long molecular dynamics simulations of the apo and Syk-ligand complexes. We considered R406, the active component of fostamatinib, as a control. The molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations demonstrated the lead1 (<math><mrow><mi>Δ</mi></mrow><mrow><msub><mi>G</mi><mrow><mrow><mrow><mi>b</mi><mi>i</mi><mi>n</mi><mi>d</mi></mrow></mrow></mrow></msub></mrow></math> = -30.35 kcal/mol) exhibited a similar binding free energy as the control (<math><mrow><mi>Δ</mi></mrow><mrow><msub><mi>G</mi><mrow><mrow><mrow><mi>b</mi><mi>i</mi><mi>n</mi><mi>d</mi></mrow></mrow></mrow></msub></mrow></math>= -29.82 kcal/mol). The Syk stabilizing effect of lead1 was also indicated in its network features, sampling space, and residual correlation motion analysis. We further generated 100 structural analogues of lead1 using deep learning, and one of the analogues displayed a better binding free energy (<math><mrow><mi>Δ</mi></mrow><mrow><msub><mi>G</mi><mrow><mrow><mrow><mi>b</mi><mi>i</mi><mi>n</mi><mi>d</mi></mrow></mrow></mrow></msub></mrow></math>= -47.58 kcal/mol) compared to the control or lead1, facilitated by more favourable van der Waals interactions and lesser binding-opposing net polar forces. This analogue may be further exploited to develop effective therapeutics against Syk-associated diseases after validation in vitro and in vivo.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"1-29"},"PeriodicalIF":3.0,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50162771","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