Molecular Diversity最新文献_第9页

Identify critical genes of breast cancer and corresponding leading natural product compounds of potential therapeutic targets. 确定乳腺癌的关键基因和相应的潜在治疗靶点的主要天然产物化合物。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-12-10 DOI: 10.1007/s11030-024-11035-z

Xiaokai Fan, Le Xin, Xuan Yu, Maoxuan Liu, Joong Sup Shim, Gui Yang, Liang Chen

{"title":"Identify critical genes of breast cancer and corresponding leading natural product compounds of potential therapeutic targets.","authors":"Xiaokai Fan, Le Xin, Xuan Yu, Maoxuan Liu, Joong Sup Shim, Gui Yang, Liang Chen","doi":"10.1007/s11030-024-11035-z","DOIUrl":"https://doi.org/10.1007/s11030-024-11035-z","url":null,"abstract":"Breast cancer is a leading cause of cancer mortality among women globally, with over 2.26 million new cases annually, according to GLOBOCAN 2020. This accounts for approximately 25% of all new female cancers and 15.5% of female cancer deaths. To address this critical public health challenge, we conducted a multi-omics study aimed at identifying hub genes, therapeutic targets, and potential natural product-based therapies. We employed weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis to pinpoint hub genes in breast cancer. Regulatory networks for these genes were constructed by re-analyzing chromatin immunoprecipitation sequencing (ChIP-seq) data from breast cancer cell lines. Additionally, single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) were utilized to characterize hub gene expression profiles and their relationships with immune cell clusters and tumor microenvironments. Survival analysis based on mRNA and protein expression levels identified prognostic factors and potential therapeutic targets. Lastly, large-scale virtual screening of natural product compounds revealed leading compounds that target squalene epoxidase (SQLE). Our multi-omics analysis paves the way for more effective clinical treatments for breast cancer.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ring opening of epoxides: a facile approach towards the synthesis of polyketides and related stereoenriched natural products: a review. 环氧化物的开环：合成多酮和相关立体富集天然产物的简便方法：综述。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-12-09 DOI: 10.1007/s11030-024-11057-7

Madiha Hanif, Asim Mansha, Kulsoom Ghulam Ali, Muhammad Athar Saeed, Shahid Mahmood, Aijaz Rasool Chaudhry, Ahmad Irfan, Aqsa Mushtaq, Ameer Fawad Zahoor

引用次数: 0

Repurposed drugs as PCSK9-LDLR disruptors for lipid lowering and cardiovascular disease therapeutics. 作为PCSK9-LDLR干扰物的再用途药物用于降脂和心血管疾病治疗。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-12-08 DOI: 10.1007/s11030-024-11063-9

Shelly Singhal Nee Shelly Aggarwal, Divpreet Kaur, Daman Saluja, Kamna Srivastava

{"title":"Repurposed drugs as PCSK9-LDLR disruptors for lipid lowering and cardiovascular disease therapeutics.","authors":"Shelly Singhal Nee Shelly Aggarwal, Divpreet Kaur, Daman Saluja, Kamna Srivastava","doi":"10.1007/s11030-024-11063-9","DOIUrl":"https://doi.org/10.1007/s11030-024-11063-9","url":null,"abstract":"The PCSK9 protein binds to LDL receptors (LDLR), leading to their degradation and reduced expression on cell surfaces. This decreased the clearance of LDL cholesterol from the bloodstream, thereby increasing the risk of coronary artery diseases. Targeting the PCSK9-LDL receptor interaction is crucial for regulating LDL cholesterol levels and preventing cardiovascular disease. This study aims to screen low molecular weight inhibitors to disrupt the PCSK9-LDLR interaction. We employed a comprehensive approach combining high-throughput virtual screening of DrugBank database, followed by molecular docking studies using CDOCKER and flexible docking methods. The top four lead compounds were further validated through molecular dynamics (MD) simulations and binding free energy calculations using MM-PBSA. Finally, the in vitro assay confirmed that Benazepril and Quinapril exhibited the highest potency as PCSK9-LDLR disruptors among the top candidates. These lead compounds have the potential to be repurposed as lipid-lowering agents for the treatment of cardiovascular diseases, offering a promising therapeutic strategy.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

iDCNNPred: an interpretable deep learning model for virtual screening and identification of PI3Ka inhibitors against triple-negative breast cancer. iDCNNPred：一个可解释的深度学习模型，用于三阴性乳腺癌PI3Ka抑制剂的虚拟筛选和鉴定。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-12-08 DOI: 10.1007/s11030-024-11055-9

Ravishankar Jaiswal, Girdhar Bhati, Shakil Ahmed, Mohammad Imran Siddiqi

{"title":"iDCNNPred: an interpretable deep learning model for virtual screening and identification of PI3Ka inhibitors against triple-negative breast cancer.","authors":"Ravishankar Jaiswal, Girdhar Bhati, Shakil Ahmed, Mohammad Imran Siddiqi","doi":"10.1007/s11030-024-11055-9","DOIUrl":"https://doi.org/10.1007/s11030-024-11055-9","url":null,"abstract":"Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and HER2 expression, accounting for 15-20% of breast cancer cases. It is challenging due to low therapeutic response, heterogeneity, and aggressiveness. The PI3Ka isoform is a promising therapeutic target, often hyperactivated in TNBC, contributing to uncontrolled growth and cancer cell formation. We have proposed an interpretable deep convolutional neural network prediction (iDCNNPred) system using 2D molecular images to classify bioactivity and identify potential PI3Ka inhibitors. We built Custom-DCNN models and pre-trained models such as AlexNet, SqueezeNet, and VGG19 by using the Bayesian optimization algorithm, and found that our Custom-DCNN model performed better than a pre-trained model with lower complexity and memory usage. All top-performed models were screened with the Maybridge Chemical library to find predictive hit molecules. The screened molecules were further evaluated for protein-ligand interaction with molecular docking and finally 12 promising hits were shortlisted for biological validation using in-vitro PI3K inhibition studies. After biological evaluation, 4 potent molecules with different structural moieties were identified, and these molecules present new starting scaffolds for further improvement in terms of their potency and selectivity as PI3K inhibitors with the help of medicinal chemistry efforts. Furthermore, we also showed the significance of the interpretation and visualization of the model's predictions by the Grad-CAM technique, enhancing the robustness, transparency, and interpretability of the model's predictions. The data and script files and prediction run of models used for this study to reproduce the experiment are available in the GitHub repository at https://github.com/ravishankar1307/iDCNNPred.git .","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","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 methyltransferase NSD2 enzymatic inhibitors through a multi-step structure-based drug design. 通过多步骤基于结构的药物设计鉴定潜在的甲基转移酶NSD2酶抑制剂。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-12-07 DOI: 10.1007/s11030-024-11072-8

Yunpeng Shen, Yingying Zhang, Tongyi Wu, Lixue Zhang, Benny Danilo Belviso

{"title":"Identification of potential methyltransferase NSD2 enzymatic inhibitors through a multi-step structure-based drug design.","authors":"Yunpeng Shen, Yingying Zhang, Tongyi Wu, Lixue Zhang, Benny Danilo Belviso","doi":"10.1007/s11030-024-11072-8","DOIUrl":"https://doi.org/10.1007/s11030-024-11072-8","url":null,"abstract":"Reversing aberrant protein methylation levels is widely recognized as a key focus in cancer therapy. As an essential lysine methylation regulator, NSD2 (Nuclear receptor-binding SET Domain 2, also known as WHSC1/MMSET) regulates chromatin structural sparsity and DNA repair processes. Abnormal enhancement of NSD2 methylation activity (caused by NSD2 overexpression and point mutations) has been closely related to the initiation and development of various cancers and diseases. However, the lack of selective inhibitors hinders further therapeutic intervention and limits the exploration of its biological mechanism. Therefore, this study developed an integrated approach that includes binding feature pharmacophore modeling, gradient database screening of 120 million compounds, flexible docking, and molecular dynamic simulation. This approach was used to identify hit compounds targeting the substrate/coenzyme binding site of NSD2. Subsequently, 20 lead compounds were retrieved by using molecular docking analysis and ADMET prediction. Finally, MD simulations were performed to validate the binding stability of selected drug candidates. The findings indicated that these newly obtained compounds might be potent NSD2 inhibitors. We hope the integrated virtual screening approach will provide a valuable idea for discovering novel H3K36 methyltransferase inhibitors.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Green synthesis, anti-inflammatory evaluation and molecular docking of novel pyridines via one pot multi-component reaction using ultrasonic irradiation. 超声辐照一锅多组分反应绿色合成、抗炎评价及分子对接。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-12-07 DOI: 10.1007/s11030-024-11073-7

Nadia A A Elkanzi, Ali M Ali, Mahmoud A Abdelaziz, Alaa Muqbil Alsirhani

{"title":"Green synthesis, anti-inflammatory evaluation and molecular docking of novel pyridines via one pot multi-component reaction using ultrasonic irradiation.","authors":"Nadia A A Elkanzi, Ali M Ali, Mahmoud A Abdelaziz, Alaa Muqbil Alsirhani","doi":"10.1007/s11030-024-11073-7","DOIUrl":"https://doi.org/10.1007/s11030-024-11073-7","url":null,"abstract":"In this paper, we present a green application for the synthesis of novel pyridine derivatives 4a-f via one-pot, multicomponent reaction (MCRs) of some aromatic aldehydes 1a-f with malononitrile (2) and N-(4-acetylphenyl)-4-methylbenzenesulfonamide (3) in the presence of ammonium acetate using ultrasonic irradiation (U.S) in an aqueous solvent H2O:EtOH (2:1). The structures of all synthesized pyridines 4a-f were confirmed via elemental analysis and different spectroscopic techniques. This application has many advantages such as avoiding hazardous solvents, excellent yields, inexpensive, simple application, in addition to obtain pure compounds. The anti-inflammatory activity of the newly compounds was examined with the reference drug Ibuprofen. The obtained results showed that most derivatives are promising anti-inflammatory activates. Moreover, compound 4b exhibits the most anti-inflammatory activity with a percentage of inhibition with 51.67% compared with Ibuprofen 53.96%. Furthermore, the newly compounds were studied in their molecular docking simulations against the enzyme Human Cyclooxygenase-2, with Tolfenamic Acid as a reference ligand (PDB ID: 5IKT). Compound 4b demonstrated a robust binding affinity with the target protein 5ikt, evidenced by its binding affinity score of - 11.16 kcal/mol, which is the highest among the studied compounds.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A bibliometric analysis of the Cheminformatics/QSAR literature (2000-2023) for predictive modeling in data science using the SCOPUS database. 使用SCOPUS数据库对化学信息学/QSAR文献（2000-2023）进行数据科学预测建模的文献计量学分析。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-12-05 DOI: 10.1007/s11030-024-11056-8

Arkaprava Banerjee, Kunal Roy, Paola Gramatica

引用次数: 0

Current advances in the structure-activity relationship (SAR) analysis of the old/new 18-kDa translocator protein ligands. 新旧18kda转运蛋白配体的构效关系（SAR）分析进展。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-12-04 DOI: 10.1007/s11030-024-10963-0

Priya Singh, Vijay Kumar Singh, Chandraprakash Gond, Deepika Singh, Anjani Kumar Tiwari

{"title":"Current advances in the structure-activity relationship (SAR) analysis of the old/new 18-kDa translocator protein ligands.","authors":"Priya Singh, Vijay Kumar Singh, Chandraprakash Gond, Deepika Singh, Anjani Kumar Tiwari","doi":"10.1007/s11030-024-10963-0","DOIUrl":"https://doi.org/10.1007/s11030-024-10963-0","url":null,"abstract":"The translocator protein 18 kDa (TSPO) is a crucial external mitochondrial protein involved in cholesterol translocation, which is essential for steroid production. As a primary marker of neuroinflammation, TSPO has been implicated in the development and progression of various neurodegenerative and neuropsychiatric disorders. This review highlights the structural diversity of TSPO ligands, many of which have undergone modifications from selective central benzodiazepine receptor (CBR) ligands to enhance their affinity for TSPO. The paper discusses the significant advancements in the design of these ligands, emphasizing their binding efficacy and specificity. Additionally, it provides an update on the progress of several TSPO ligands that have advanced to clinical trials. The review aims to elucidate the structure-activity relationships (SAR) that govern the interaction between TSPO and its ligands, thereby offering insights into the development of new therapeutic agents targeting TSPO for the treatment of neuroinflammatory conditions. Overall, this work provided an update on previous finding and serves as a valuable resource for researchers in the field.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis, antimicrobial, antioxidant, tyrosinase inhibitory activities, and computational studies of novel chromen[2,3-c]pyrazole derivatives. 新型铬[2,3-c]吡唑衍生物的合成、抗菌、抗氧化、酪氨酸酶抑制活性及计算研究。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-12-03 DOI: 10.1007/s11030-024-11051-z

Velmurugan Loganathan, Arunadevi Mani, Idhayadhulla Akbar, Anis Ahamed, Hissah Abdulrahman Alodaini, Desta Galona Gerbu, Aseer Manilal

{"title":"Synthesis, antimicrobial, antioxidant, tyrosinase inhibitory activities, and computational studies of novel chromen[2,3-c]pyrazole derivatives.","authors":"Velmurugan Loganathan, Arunadevi Mani, Idhayadhulla Akbar, Anis Ahamed, Hissah Abdulrahman Alodaini, Desta Galona Gerbu, Aseer Manilal","doi":"10.1007/s11030-024-11051-z","DOIUrl":"https://doi.org/10.1007/s11030-024-11051-z","url":null,"abstract":"In this study, one-pot multicomponent reactions of novel chromeno[2,3-c]pyrazole derivatives (1-14) were performed using an AlCl3 catalyst via cyclisation. Various spectral and chromatographic techniques were used to elucidate the structure of the synthesised derivatives (1-14). The synthesised compounds were then inspected for their antibacterial, antioxidant, and tyrosinase inhibition activities. An in silico screening approach was also employed to identify highly potent derivatives. Besides, we utilised density functional theory (DFT) with the B3LYP/6-31G+ (d, p) basis set to optimise the newly modified derivatives. This approach was used to calculate various properties, including electron density, electrostatic potential map, interaction strength, frontier molecular orbital energy, and reactivity characteristics. To examine the binding affinity, modes, and stability of the protein-drug complex, molecular docking with the 2Y9X protein structure were employed. The findings from DFT computations, along with physicochemical information and molecular docking binding affinity, showed promising results than standard and low active compound 1. The absorption, metabolism, and cytotoxic characteristics of all the novel derivatives were investigated in the ADMET prediction. Our findings could prove valuable in developing novel drugs for medicinal and pharmaceutical fields.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design, synthesis and antitumor activity of 4-indazolylpyrimidine derivatives as EGFR inhibitors. 4-吲哚基嘧啶衍生物EGFR抑制剂的设计、合成及抗肿瘤活性研究。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-12-03 DOI: 10.1007/s11030-024-11052-y

Ting Yang, Xiaoling He, Ting Wu, Wenqiang Zhu, Zhiwu Long, Yi Le

引用次数: 0