Molecular Diversity最新文献_第2页

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.

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.

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.

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.

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.

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.

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.

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.

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

Influence of hydrophobicity on the antimicrobial activity of helical antimicrobial peptides: a study focusing on three mastoparans.

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-12-02 DOI: 10.1007/s11030-024-11046-w

Binh Le Huy, Hai Bui Thi Phuong, Binh Nguyen Thi Thanh, Quang Tran Van, Hoang Vu Dinh, Huy Luong Xuan

{"title":"Influence of hydrophobicity on the antimicrobial activity of helical antimicrobial peptides: a study focusing on three mastoparans.","authors":"Binh Le Huy, Hai Bui Thi Phuong, Binh Nguyen Thi Thanh, Quang Tran Van, Hoang Vu Dinh, Huy Luong Xuan","doi":"10.1007/s11030-024-11046-w","DOIUrl":"https://doi.org/10.1007/s11030-024-11046-w","url":null,"abstract":"Hydrophobicity is crucial for the interaction between amphipathic antimicrobial peptides and microbial pathogens. However, it is difficult to fully understand the impact of this factor because the biological functions are also influenced by other structural properties, including peptide length, net charge, hydrophilicity, secondary structure, and hydrophobic moment. This study compares three natural antimicrobial peptides-mastoparan C, mastoparan-AF, and mastoparan L-where hydrophobicity varies but other structural features remain nearly identical. Mastoparan C, the most hydrophobic peptide, displays the highest helical content and hemolytic activity, whereas mastoparan-AF, with slightly lower hydrophobicity, demonstrates superior selectivity. In contrast, mastoparan L, the least hydrophobic peptide, exhibits the weakest antimicrobial potency and lowest hemolytic activity, despite showing the least self-assembly. Overall, this study suggests that optimal hydrophobicity, rather than the highest value, enhances antimicrobial efficacy while minimizing hemolytic activity.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765295","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