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

Identification of inhibitors for neurodegenerative diseases targeting dual leucine zipper kinase through virtual screening and molecular dynamics simulations. 通过虚拟筛选和分子动力学模拟鉴定针对神经退行性疾病的双亮氨酸拉链激酶抑制剂。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-06-01 Epub Date: 2024-06-10 DOI: 10.1080/1062936X.2024.2363195

S Koirala, S Samanta, P Kar

{"title":"Identification of inhibitors for neurodegenerative diseases targeting dual leucine zipper kinase through virtual screening and molecular dynamics simulations.","authors":"S Koirala, S Samanta, P Kar","doi":"10.1080/1062936X.2024.2363195","DOIUrl":"10.1080/1062936X.2024.2363195","url":null,"abstract":"Neurodegenerative diseases lead to a gradual decline in cognitive and motor functions due to the progressive loss of neurons in the central nervous system. The role of dual leucine zipper kinase (DLK) in regulating stress responses and neuronal death pathways highlights its significance as a target against neurodegenerative diseases. The non-availability of FDA-approved drugs emphasizes a need to identify novel DLK-inhibitors. We screened NPAtlas (Natural products) and MedChemExpress (FDA-approved) libraries to identify potent ATP-competitive DLK inhibitors. ADMET analyses identified four compounds (two natural products and two FDA-approved) with favourable features. Subsequently, we performed molecular dynamics simulations to examine the binding-stability and ligand-induced conformational dynamics. Molecular mechanics Poisson Boltzmann surface area (MM-PBSA) calculations demonstrated CID139591660, dithranol, and danthron having greater affinity, while CID156581477 showed lower affinity than control sunitinib. PCA and network analysis results indicated structural and network alteration post-ligand binding. Furthermore, we identified an analogue of CID156581477 using the deep learning-based web server DeLA Drug which demonstrated a higher affinity than its parent compound and the control and identified several crucial interacting residues. Overall, our study provides significant theoretical guidance for designing potent novel DLK inhibitors and compounds that could emerge as promising drug candidates against DLK following laboratory validation.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"457-482"},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296640","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

Fragment-based QSAR study to explore the structural requirements of DPP-4 inhibitors: a stepping stone towards better type 2 diabetes mellitus management. 基于片段的 QSAR 研究探索 DPP-4 抑制剂的结构要求：改善 2 型糖尿病管理的踏脚石。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-06-01 Epub Date: 2024-06-21 DOI: 10.1080/1062936X.2024.2366886

P K Dey, R Dutta, M Ray, P Jakkula, S Banerjee, I A Qureshi, S Gayen, S A Amin

{"title":"Fragment-based QSAR study to explore the structural requirements of DPP-4 inhibitors: a stepping stone towards better type 2 diabetes mellitus management.","authors":"P K Dey, R Dutta, M Ray, P Jakkula, S Banerjee, I A Qureshi, S Gayen, S A Amin","doi":"10.1080/1062936X.2024.2366886","DOIUrl":"10.1080/1062936X.2024.2366886","url":null,"abstract":"Dipeptidyl peptidase-4 (DPP-4) inhibitors belong to a prominent group of pharmaceutical agents that are used in the governance of type 2 diabetes mellitus (T2DM). They exert their antidiabetic effects by inhibiting the incretin hormones like glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide which, play a pivotal role in the regulation of blood glucose homoeostasis in our body. DPP-4 inhibitors have emerged as an important class of oral antidiabetic drugs for the treatment of T2DM. Surprisingly, only a few 2D-QSAR studies have been reported on DPP-4 inhibitors. Here, fragment-based QSAR (Laplacian-modified Bayesian modelling and Recursive partitioning (RP) approaches have been utilized on a dataset of 108 DPP-4 inhibitors to achieve a deeper understanding of the association among their molecular structures. The Bayesian analysis demonstrated satisfactory ROC values for the training as well as the test sets. Meanwhile, the RP analysis resulted in decision tree 3 with 2 leaves (Tree 3: 2 leaves). This present study is an effort to get an insight into the pivotal fragments modulating DPP-4 inhibition.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"483-504"},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432666","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

HT_PREDICT: a machine learning-based computational open-source tool for screening HDAC6 inhibitors. HT_PREDICT：基于机器学习的计算开源工具，用于筛选 HDAC6 抑制剂。

IF 2.3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-06-01 Epub Date: 2024-07-15 DOI: 10.1080/1062936X.2024.2371155

O V Tinkov, V N Osipov, A V Kolotaev, D S Khachatryan, V Y Grigorev

引用次数: 0

Anti-inflammatory action of new hybrid N-acyl-[1,2]dithiolo-[3,4-c]quinoline-1-thione. 新型混合 N-酰基-[1,2]二硫环戊-[3,4-c]喹啉-1-硫酮的抗炎作用。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-05-01 Epub Date: 2024-05-22 DOI: 10.1080/1062936X.2024.2347965

S M Medvedeva, A Petrou, M Fesatidou, A Gavalas, A A Geronikaki, P I Savosina, D S Druzhilovskiy, V V Poroikov, K S Shikhaliev, V G Kartsev

{"title":"Anti-inflammatory action of new hybrid N-acyl-[1,2]dithiolo-[3,4-c]quinoline-1-thione.","authors":"S M Medvedeva, A Petrou, M Fesatidou, A Gavalas, A A Geronikaki, P I Savosina, D S Druzhilovskiy, V V Poroikov, K S Shikhaliev, V G Kartsev","doi":"10.1080/1062936X.2024.2347965","DOIUrl":"10.1080/1062936X.2024.2347965","url":null,"abstract":"Most of pharmaceutical agents display a number of biological activities. It is obvious that testing even one compound for thousands of biological activities is not practically possible. A computer-aided prediction is therefore the method of choice in this case to select the most promising bioassays for particular compounds. Using the PASS Online software, we determined the probable anti-inflammatory action of the 12 new hybrid dithioloquinolinethiones derivatives. Chemical similarity search in the World-Wide Approved Drugs (WWAD) and DrugBank databases did not reveal close structural analogues with the anti-inflammatory action. Experimental testing of anti-inflammatory activity of the synthesized compounds in the carrageenan-induced inflammation mouse model confirmed the computational predictions. The anti-inflammatory activity of the studied compounds (2a, 3a-3k except for 3j) varied between 52.97% and 68.74%, being higher than the reference drug indomethacin (47%). The most active compounds appeared to be 3h (68.74%), 3k (66.91%) and 3b (63.74%) followed by 3e (61.50%). Thus, based on the in silico predictions a novel class of anti-inflammatory agents was discovered.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"343-366"},"PeriodicalIF":3.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081520","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 different classification-dependent QSAR modelling strategies for HDAC3 inhibitors in search of meaningful structural contributors. 探索 HDAC3 抑制剂的不同分类依赖 QSAR 建模策略，寻找有意义的结构贡献者。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-05-01 Epub Date: 2024-05-17 DOI: 10.1080/1062936X.2024.2350504

T Jha, R Jana, S Banerjee, S K Baidya, S A Amin, S Gayen, B Ghosh, N Adhikari

{"title":"Exploring different classification-dependent QSAR modelling strategies for HDAC3 inhibitors in search of meaningful structural contributors.","authors":"T Jha, R Jana, S Banerjee, S K Baidya, S A Amin, S Gayen, B Ghosh, N Adhikari","doi":"10.1080/1062936X.2024.2350504","DOIUrl":"10.1080/1062936X.2024.2350504","url":null,"abstract":"Histone deacetylase 3 (HDAC3), a Zn2+-dependent class I HDACs, contributes to numerous disorders such as neurodegenerative disorders, diabetes, cardiovascular disease, kidney disease and several types of cancers. Therefore, the development of novel and selective HDAC3 inhibitors might be promising to combat such diseases. Here, different classification-based molecular modelling studies such as Bayesian classification, recursive partitioning (RP), SARpy and linear discriminant analysis (LDA) were conducted on a set of HDAC3 inhibitors to pinpoint essential structural requirements contributing to HDAC3 inhibition followed by molecular docking study and molecular dynamics (MD) simulation analyses. The current study revealed the importance of hydroxamate function for Zn2+ chelation as well as hydrogen bonding interaction with Tyr298 residue. The importance of hydroxamate function for higher HDAC3 inhibition was noticed in the case of Bayesian classification, recursive partitioning and SARpy models. Also, the importance of substituted thiazole ring was revealed, whereas the presence of linear alkyl groups with carboxylic acid function, any type of ester function, benzodiazepine moiety and methoxy group in the molecular structure can be detrimental to HDAC3 inhibition. Therefore, this study can aid in the design and discovery of effective novel HDAC3 inhibitors in the future.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"367-389"},"PeriodicalIF":3.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959029","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

Potential antioxidant, α-glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of major constituents isolated from Alpinia officinarum hance rhizomes: computational studies and in vitro validation. 从高山植物根茎中分离的主要成分的潜在抗氧化、α-葡萄糖苷酶、丁酰胆碱酯酶和乙酰胆碱酯酶抑制活性：计算研究和体外验证。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-05-01 Epub Date: 2024-05-21 DOI: 10.1080/1062936X.2024.2352725

H A Al Garni, A M El-Halawany, A E Koshak, A M Malebari, A A Alzain, G A Mohamed, S R M Ibrahim, N S El-Sayed, H M Abdallah

{"title":"Potential antioxidant, α-glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of major constituents isolated from Alpinia officinarum hance rhizomes: computational studies and in vitro validation.","authors":"H A Al Garni, A M El-Halawany, A E Koshak, A M Malebari, A A Alzain, G A Mohamed, S R M Ibrahim, N S El-Sayed, H M Abdallah","doi":"10.1080/1062936X.2024.2352725","DOIUrl":"10.1080/1062936X.2024.2352725","url":null,"abstract":"Alpinia officinarum is a commonly used spice with proven folk uses in various traditional medicines. In the current study, six compounds were isolated from its rhizomes, compounds 1-3 were identified as diarylheptanoids, while 4-6 were identified as flavonoids and phenolic acids. The isolated compounds were subjected to virtual screening against α-glucosidase, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) enzymes to evaluate their potential antidiabetic and anti-Alzheimer's activities. Molecular docking and dynamics studies revealed that 3 exhibited a strong binding affinity to human a α- glucosidase crystal structure compared to acarbose. Furthermore, 2 and 5 demonstrated high potency against AChE. The virtual screening results were further supported by in vitro assays, which assessed the compounds' effects on α-glucosidase, cholinesterases, and their antioxidant activities. 5-Hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenylheptan-3-one (2) showed potent antioxidant effect in both ABTs and ORAC assays, while p-hydroxy cinnamic acid (6) was the most potent in the ORAC assay. In contrary, kaempferide (4) and galangin (5) showed the most potent effect in metal chelation assay. 5-Hydroxy-1,7-diphenylhepta-4,6-dien-3-one (3) and 6 revealed the most potent effect as α-glucosidase inhibitors where compound 3 showed more potent effect compared to acarbose. Galangin (5) revealed a higher selectivity to BChE, while 2 showed the most potent activity to (AChE).","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"391-410"},"PeriodicalIF":3.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071284","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 inhibitory action of betulinic acid on key digestive enzymes linked to diabetes via in vitro and computational models: approaches to anti-diabetic mechanisms. 通过体外和计算模型探索白桦脂酸对与糖尿病有关的关键消化酶的抑制作用：抗糖尿病机制的方法。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-05-01 Epub Date: 2024-05-20 DOI: 10.1080/1062936X.2024.2352729

V F Salau, O L Erukainure, A Aljoundi, E O Akintemi, G Elamin, O A Odewole

{"title":"Exploring the inhibitory action of betulinic acid on key digestive enzymes linked to diabetes via in vitro and computational models: approaches to anti-diabetic mechanisms.","authors":"V F Salau, O L Erukainure, A Aljoundi, E O Akintemi, G Elamin, O A Odewole","doi":"10.1080/1062936X.2024.2352729","DOIUrl":"10.1080/1062936X.2024.2352729","url":null,"abstract":"Phytochemicals are now increasingly exploited as remedial agents for the management of diabetes due to side effects attributable to commercial antidiabetic agents. This study investigated the structural and molecular mechanisms by which betulinic acid exhibits its antidiabetic effect via in vitro and computational techniques. In vitro antidiabetic potential was analysed via on α-amylase, α-glucosidase, pancreatic lipase and α-chymotrypsin inhibitory assays. Its structural and molecular inhibitory mechanisms were investigated using Density Functional Theory (DFT) analysis, molecular docking and molecular dynamics (MD) simulation. Betulinic acid significantly (p < 0.05) inhibited α-amylase, α-glucosidase, pancreatic lipase and α-chymotrypsin enzymes with IC50 of 70.02 μg/mL, 0.27 μg/mL, 1.70 μg/mL and 8.44 μg/mL, respectively. According to DFT studies, betulinic acid possesses similar reaction in gaseous phase and water due to close values observed for highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LUMO) and the chemical descriptors. The dipole moment indicates that betulinic acid has high polarity. Molecular electrostatic potential surface revealed the electrophilic and nucleophilic attack-prone atoms of the molecule. Molecular dynamic studies revealed a stable complex between betulinic acid and α-amylase, α-glucosidase, pancreatic lipase and α-chymotrypsin. The study elucidated the potent antidiabetic properties of betulinic acid by revealing its conformational inhibitory mode of action on enzymes involved in the onset of diabetes.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"411-432"},"PeriodicalIF":3.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066071","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 chemical space, scaffold diversity, and activity landscape of spleen tyrosine kinase active inhibitors. 探索脾脏酪氨酸激酶活性抑制剂的化学空间、支架多样性和活性格局。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-04-01 Epub Date: 2024-05-01 DOI: 10.1080/1062936X.2024.2345618

Danishuddin, M Z Malik, M Kashif, S Haque, J J Kim

{"title":"Exploring chemical space, scaffold diversity, and activity landscape of spleen tyrosine kinase active inhibitors.","authors":"Danishuddin, M Z Malik, M Kashif, S Haque, J J Kim","doi":"10.1080/1062936X.2024.2345618","DOIUrl":"https://doi.org/10.1080/1062936X.2024.2345618","url":null,"abstract":"This study aims to comprehensively characterize 576 inhibitors targeting Spleen Tyrosine Kinase (SYK), a non-receptor tyrosine kinase primarily found in haematopoietic cells, with significant relevance to B-cell receptor function. The objective is to gain insights into the structural requirements essential for potent activity, with implications for various therapeutic applications. Through chemoinformatic analyses, we focus on exploring the chemical space, scaffold diversity, and structure-activity relationships (SAR). By leveraging ECFP4 and MACCS fingerprints, we elucidate the relationship between chemical compounds and visualize the network using RDKit and NetworkX platforms. Additionally, compound clustering and visualization of the associated chemical space aid in understanding overall diversity. The outcomes include identifying consensus diversity patterns to assess global chemical space diversity. Furthermore, incorporating pairwise activity differences enhances the activity landscape visualization, revealing heterogeneous SAR patterns. The dataset analysed in this work has three activity cliff generators, CHEMBL3415598, CHEMBL4780257, and CHEMBL3265037, compounds with high affinity to SYK are very similar to compounds analogues with reasonable potency differences. Overall, this study provides a critical analysis of SYK inhibitors, uncovering potential scaffolds and chemical moieties crucial for their activity, thereby advancing the understanding of their therapeutic potential.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":"35 4","pages":"325-342"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852785","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

Quantitative structure-property relationship modelling on autoignition temperature: evaluation and comparative analysis. 关于自燃温度的定量结构-性能关系模型：评估和比较分析。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-03-01 Epub Date: 2024-02-19 DOI: 10.1080/1062936X.2024.2312527

J Chen, L Zhu, J Wang

引用次数: 0

Development of a standardized methodology for transfer learning with QSAR models: a purely data-driven approach for source task selection. 开发 QSAR 模型迁移学习的标准化方法：纯数据驱动的源任务选择方法。

IF 3 3区环境科学与生态学

SAR and QSAR in Environmental Research Pub Date : 2024-03-01 Epub Date: 2024-02-05 DOI: 10.1080/1062936X.2024.2311693

L Melo, L Scotti, M T Scotti

{"title":"Development of a standardized methodology for transfer learning with QSAR models: a purely data-driven approach for source task selection.","authors":"L Melo, L Scotti, M T Scotti","doi":"10.1080/1062936X.2024.2311693","DOIUrl":"10.1080/1062936X.2024.2311693","url":null,"abstract":"Transfer learning is a machine learning technique that works well with chemical endpoints, with several papers confirming its efficiency. Although effective, because the choice of source/assistant tasks is non-trivial, the application of this technique is severely limited by the domain knowledge of the modeller. Considering this limitation, we developed a purely data-driven approach for source task selection that abstracts the need for domain knowledge. To achieve this, we created a supervised learning setting in which transfer outcome (positive/negative) is the variable to be predicted, and a set of six transferability metrics, calculated based on information from target and source datasets, are the features for prediction. We used the ChEMBL database to generate 100,000 transfers using random pairing, and with these transfers, we trained and evaluated our transferability prediction model (TP-Model). Our TP-Model achieved a 135-fold increase in precision while achieving a sensitivity of 92%, demonstrating a clear superiority against random search. In addition, we observed that transfer learning could provide considerable performance increases when applicable, with an average Matthews Correlation Coefficient (MCC) increase of 0.19 when using a single source and an average MCC increase of 0.44 when using multiple sources.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"183-198"},"PeriodicalIF":3.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681499","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