Molecular Diversity最新文献_第8页

Antiviral efficacy of honey bee antimicrobial peptides against SARS-CoV-2. 蜜蜂抗菌肽对SARS-CoV-2的抗病毒作用

IF 3.8 2区化学

Molecular Diversity Pub Date : 2025-08-16 DOI: 10.1007/s11030-025-11325-0

Roy Dinata, Piyush Baindara, Chettri Arati, Guruswami Gurusubramanian

{"title":"Antiviral efficacy of honey bee antimicrobial peptides against SARS-CoV-2.","authors":"Roy Dinata, Piyush Baindara, Chettri Arati, Guruswami Gurusubramanian","doi":"10.1007/s11030-025-11325-0","DOIUrl":"https://doi.org/10.1007/s11030-025-11325-0","url":null,"abstract":"The COVID-19 pandemic continues to pose severe health and economic challenges, exacerbated by emerging antiviral drug resistance. As of now, there are several vaccines and a few FDA-approved drugs available; however, due to the emergence of antiviral drug resistance still there is a need for novel strategies and antiviral drugs. This study investigates honey bee-derived antimicrobial peptides (BAMPs) as potential multi-target antiviral agents against SARS-CoV-2. A total of 82 BAMPs from eight bee species, classified into seven peptide classes, were screened for favorable pharmacokinetic and pharmacodynamic properties. Finally, seventeen BAMPs were selected, modeled, and validated for further structural studies. Molecular docking revealed strong binding affinities with key viral and host targets, surpassing several FDA-approved antivirals. These interactions suggest BAMPs may inhibit viral entry, replication, and dissemination. Further, molecular dynamics simulation studies confirmed the stability, compactness, and flexibility of the docked complexes. Overall, present study highlight BAMPs as promising candidates for SARS-CoV-2 therapeutics, while warranting further in vitro and in vivo validation.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861996","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

Flavonol derivatives containing pyrazole oxime ether: design, synthesis, and anti-TMV activity. 含吡唑肟醚类黄酮醇衍生物的设计、合成及抗tmv活性。

IF 3.8 2区化学

Molecular Diversity Pub Date : 2025-08-15 DOI: 10.1007/s11030-025-11318-z

Chunmei Hu, Dan Shen, Yujiao Qiu, Fang Tian, Qingxue Hu, Xiaoyan Pan, Ying Yang, Wanqiu Peng, Xianghui Ruan, Wei Xue

{"title":"Flavonol derivatives containing pyrazole oxime ether: design, synthesis, and anti-TMV activity.","authors":"Chunmei Hu, Dan Shen, Yujiao Qiu, Fang Tian, Qingxue Hu, Xiaoyan Pan, Ying Yang, Wanqiu Peng, Xianghui Ruan, Wei Xue","doi":"10.1007/s11030-025-11318-z","DOIUrl":"https://doi.org/10.1007/s11030-025-11318-z","url":null,"abstract":"A series of flavonol derivatives containing pyrazole oxime ether moieties were designed and synthesized. In vivo antiviral assays revealed that some compounds exhibited remarkable inhibitory effects against tobacco mosaic virus (TMV). Among them, Both the curative activity (EC50 = 88.9 μg/mL) and protective activity (EC50 = 107.5 μg/mL) of H13 were shown to be significantly superior to those of the reference agent ningnanmycin (NNM) (208.4 μg/mL and 190.1 μg/mL, respectively). Mechanistic studies indicated that both microscale thermophoresis (MST) experiments and molecular docking results demonstrate that H13 exhibits stronger binding capacity and affinity for the tobacco mosaic virus coat protein (TMV-CP) than NNM. Density functional theory (DFT) calculations further revealed higher chemical reactivity of H13. Additionally, H13 treatment significantly enhanced chlorophyll content in tobacco leaves, improving photosynthetic efficiency, while reduced malondialdehyde (MDA) levels indicated strengthened disease resistance. ADME property prediction suggested no significant ocular toxicity or hERG inhibition risk for H13. Plant experiments confirmed that H13 caused no adverse effects on tobacco seed germination or leaf growth.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854163","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

Druggability assessments of small peptides as protein-protein interaction inhibitors targeting EED-EZH2 binding within the Polycomb Repressive Complex 2 (PRC2), an epigenetic regulator. 小肽作为蛋白-蛋白相互作用抑制剂靶向聚梳抑制复合体2 （PRC2）内ed - ezh2结合的可药物性评估。

IF 3.8 2区化学

Molecular Diversity Pub Date : 2025-08-15 DOI: 10.1007/s11030-025-11321-4

Varun Thachan Kundil, Sharanya C Suresh, Sreeja Chellappan, Anupama Kizhakkepurayil, Soorej Muhammad Basheer, Arun Kumar Gangadharan

{"title":"Druggability assessments of small peptides as protein-protein interaction inhibitors targeting EED-EZH2 binding within the Polycomb Repressive Complex 2 (PRC2), an epigenetic regulator.","authors":"Varun Thachan Kundil, Sharanya C Suresh, Sreeja Chellappan, Anupama Kizhakkepurayil, Soorej Muhammad Basheer, Arun Kumar Gangadharan","doi":"10.1007/s11030-025-11321-4","DOIUrl":"https://doi.org/10.1007/s11030-025-11321-4","url":null,"abstract":"Histone methylation is a key epigenetic modification involved in gene silencing and plays a crucial role in chromatin remodelling. Polycomb repressive complex 2 (PRC2), a histone-modifying complex, has been implicated in various diseases, including cancers and genetic disorders. Since PRC2 is a multi-protein complex, the structural interactions among its component proteins are essential for its proper function. Consequently, inhibiting the formation of this complex is considered an effective strategy to block PRC2 activity. This research evaluated small peptides as protein-protein interaction (PPI) inhibitors to disrupt the binding between two key PRC2 components, Embryonic Ectoderm Development (EED) and Enhancer of Zeste Homolog 2 (EZH2), using computational approaches. Initially, pharmacophore models were generated based on the structural features of EED and EZH2, followed by pharmacophore-based virtual screening to identify tetra-peptide candidates from a library of 160,000 compounds. Molecular docking, molecular dynamics simulations, principal component analysis (PCA), dynamic cross-correlation matrices (DCCM) analysis, binding energy estimation, toxicity prediction, and membrane permeability predictions were employed to filter the most promising leads. The study identified several tetra-peptides, including WSYN, HQHE, WVYS, HYEN, WHAE, IPWP, KNNQ, CGKQ, and CIHN, as strong EED-EZH2 PPI inhibitors. Molecular docking, MD simulations, and binding energy analysis revealed stable and effective binding of the peptides to the EZH2-interacting region of EED, further supported by PCA analysis. Their non-toxic, drug-like properties and membrane permeability highlight their strong potential as lead candidates for developing EED-EZH2 interaction inhibitors.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854162","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

Asymmetric C2-functionalization of indoles via visible-light-promoted three-component reaction. 可见光促进的三组分反应中吲哚的不对称c2功能化。

IF 3.8 2区化学

Molecular Diversity Pub Date : 2025-08-15 DOI: 10.1007/s11030-025-11319-y

Han-Peng Pan, Xiao-Ying Hu, Jun-Hui Luo, Zhao-Jie Fu, Xin-Yi Yao, Meng-Yan Ran, Fang-Xin Wang, Xiang-Zhi Zhang

引用次数: 0

Structural and computational analysis of monkeypox virus methyltransferase: dynamic inhibition mechanisms and their implications for antiviral design. 猴痘病毒甲基转移酶的结构和计算分析：动态抑制机制及其对抗病毒设计的意义。

IF 3.8 2区化学

Molecular Diversity Pub Date : 2025-08-13 DOI: 10.1007/s11030-025-11258-8

Muhammad Waqas, Syed Ahsan Shahid, Muhammad Shahab, Yongkun Zhu, Aamir Fahira, Zunnan Huang

{"title":"Structural and computational analysis of monkeypox virus methyltransferase: dynamic inhibition mechanisms and their implications for antiviral design.","authors":"Muhammad Waqas, Syed Ahsan Shahid, Muhammad Shahab, Yongkun Zhu, Aamir Fahira, Zunnan Huang","doi":"10.1007/s11030-025-11258-8","DOIUrl":"https://doi.org/10.1007/s11030-025-11258-8","url":null,"abstract":"Monkeypox (Mpox), an emerging global health threat, necessitates the development of effective antiviral agents. In our study, we selected the Mpox virus methyltransferase VP39 (MTase) protein due to its role in viral replication and immune evasion. The MTase protein is essential in Mpox and is associated with similar replication mechanisms in other viruses like COVID-19, making it a broad-spectrum target for antiviral therapy. We screened the ZINC20 in-stock compounds against the MTase protein, utilizing molecular docking, accompanied by pharmacokinetic analysis to assess their binding affinity and drug-like properties, and conducted molecular dynamic simulations to observe the stability and conformational changes of the protein-ligand complexes over time. The docking results revealed that the highest binding energy was exhibited by ZINC257233856, with a value of - 7.68 kcal/mol, indicating a strong interaction with the MTase protein followed by the other compounds. All the compounds selected for the study showed consistently acceptable safety profiles. Molecular dynamics simulations demonstrated that the selected compounds, specifically ZINC257233856, showed significant stability within the MTase binding pocket. Additionally, solvation thermodynamics were investigated using Grid Inhomogeneous Solvation Theory (GIST), revealing key hydration patterns and thermodynamic hotspots that further support the binding stability of top-ranked inhibitors. Thus, our study demonstrates the promising potential of selected compounds as therapeutic options against Mpox. Our findings lay a foundational basis for further clinical investigation and the development of effective treatments.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833686","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

Computational discovery of ATP-competitive GSK3β inhibitors using database-driven virtual screening and deep learning. 使用数据库驱动的虚拟筛选和深度学习计算发现atp竞争性GSK3β抑制剂。

IF 3.8 2区化学

Molecular Diversity Pub Date : 2025-08-13 DOI: 10.1007/s11030-025-11320-5

Tanmaykumar Varma, Pradnya Kamble, R Rajkumar, Prabha Garg

{"title":"Computational discovery of ATP-competitive GSK3β inhibitors using database-driven virtual screening and deep learning.","authors":"Tanmaykumar Varma, Pradnya Kamble, R Rajkumar, Prabha Garg","doi":"10.1007/s11030-025-11320-5","DOIUrl":"https://doi.org/10.1007/s11030-025-11320-5","url":null,"abstract":"Glycogen synthase kinase 3 beta (GSK3β) is a pivotal serine/threonine kinase implicated in diverse pathological conditions, making it a compelling target for therapeutic intervention. In this study, we employed a structure-based drug discovery approach to identify novel ATP-competitive GSK3β inhibitors through a multi-tiered computational framework. Reported inhibitors from various repositories were systematically analysed to establish physicochemical and interaction-based filters, facilitating the rational curation of screening candidates. Toxicity assessment via Derek Nexus further refined the selection, yielding seven lead compounds with optimal docking scores, robust interaction profiles, and adherence to drug-likeness criteria. Molecular dynamics simulations over 300 ns validated the stability of protein-ligand complexes with root mean square deviation, radius of gyration, and binding free energy calculations, substantiating sustained interactions. Key residues, including Lys85, Asp133, and Val135, were identified as critical for ligand stabilisation, corroborating reported inhibitor-binding mechanisms. Additionally, a deep learning based prediction model, GSK3BPred, was developed to classify potential GSK3β inhibitors. The GSK3BPred model is publicly available at https://github.com/PGlab-NIPER/GSK3BPred.git . This integrative computational strategy offers valuable insights into the discovery of novel ATP-competitive GSK3β inhibitors and lays a foundation for future experimental validation and optimization.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844005","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 SARS-CoV‑2 main protease inhibitory activities of 2-arylthiomethyl-6-bromoindole derivatives. 2-芳基硫甲基-6-溴吲哚衍生物的设计、合成及其对SARS-CoV - 2主要蛋白酶的抑制活性

IF 3.8 2区化学

Molecular Diversity Pub Date : 2025-08-13 DOI: 10.1007/s11030-025-11308-1

Zong Xinyu, Li Xiaoyang, Liu Shiyu, Jin Guanxuan, Yang Kan, Wang Chunnong, Li Longfei, Cao Fei, Li Wan

引用次数: 0

Mol-SGGI: an attention-guided comprehensive molecular multi-representation learning and adaptive fusion framework for molecular property prediction. 基于注意引导的综合分子多表示学习和自适应融合框架。

IF 3.8 2区化学

Molecular Diversity Pub Date : 2025-08-10 DOI: 10.1007/s11030-025-11294-4

Lei Ma, Chunyun Pu, Dangguo Shao, Sanli Yi

{"title":"Mol-SGGI: an attention-guided comprehensive molecular multi-representation learning and adaptive fusion framework for molecular property prediction.","authors":"Lei Ma, Chunyun Pu, Dangguo Shao, Sanli Yi","doi":"10.1007/s11030-025-11294-4","DOIUrl":"https://doi.org/10.1007/s11030-025-11294-4","url":null,"abstract":"Molecular property prediction is pivotal for drug discovery, offering significant potential to accelerate development and reduce costs. With the rapid development of artificial intelligence, molecular representation methods have become increasingly diversified. However, existing methods still have obvious deficiencies in the comprehensiveness of molecular representation and the effectiveness of feature fusion: single representation methods often can only capture part of a molecule's features, while multi-representation methods focus on limited combinations and use simple fusion strategies. To address these issues, we propose Mol-SGGI, a comprehensive multi-representation learning framework that integrates four molecular representations: sequences, 2D graph structures, 3D geometric structures, and images. For each representation, we design specialized modules for extracting features and introduce appropriate attention mechanisms in each module to effectively capture the structural and chemical information of the molecule. Additionally, we propose an attention-guided adaptive weighted fusion module, which achieves multimodal feature alignment through contrastive learning and dynamically adjusts fusion weights. Experimental results on eight molecular property prediction tasks show that our model significantly outperforms the majority of existing methods.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811586","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 new dasatinib analogues targeting mutated BCR-ABL1: virtual screening, molecular docking, and dynamics simulations studies. 靶向突变BCR-ABL1的新型达沙替尼类似物的鉴定：虚拟筛选、分子对接和动力学模拟研究

IF 3.8 2区化学

Molecular Diversity Pub Date : 2025-08-09 DOI: 10.1007/s11030-025-11310-7

Mohammad Jahoor Alam, Arshad Jamal, Shaik Daria Hussain, Shahzaib Ahamad, Dinesh Gupta, Ashanul Haque

{"title":"Identification of new dasatinib analogues targeting mutated BCR-ABL1: virtual screening, molecular docking, and dynamics simulations studies.","authors":"Mohammad Jahoor Alam, Arshad Jamal, Shaik Daria Hussain, Shahzaib Ahamad, Dinesh Gupta, Ashanul Haque","doi":"10.1007/s11030-025-11310-7","DOIUrl":"https://doi.org/10.1007/s11030-025-11310-7","url":null,"abstract":"Drug resistance is a major challenge in cancer chemotherapy and accounts for a majority of cancer-related deaths globally. One of the well-identified and characterised mechanisms of drug resistance in chronic myeloid leukaemia (CML) is the presence of BCR-ABL1 mutations, which is responsible for resistance against first-line tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, and nilotinib. In the present work, we first performed a three-tier virtual screening against the human tyrosine kinase ABL1 protein (PDB ID: 2GQG). Top-performing compounds were then selected for molecular dynamics (MD) simulation studies at 500 ns to understand their affinity, dynamics, and stability with the target protein. Finally, density functional theory (DFT) studies at the B3LYP/6-31G* level of theory were conducted to elucidate the molecular features of the identified compounds. Based on the docking scores (-14.80 to -13.79 kcal/mol) and ADMET profiles, we identify 45375848, 88575518, and 23589024 as the most promising candidates. All three compounds contained N-(2-chloro-6-methylphenyl)-2-(methylamino) thiazole-5 carboxamide as the common fragment. MD parameters (RMSD, RMSF and SSE) further complemented the docking results, showing stabilisation of the ABL1 protein in the presence of identified compounds. High drug-likeness, acceptable pharmacokinetic profile and other molecular features warrant the drug-like behaviour of the compounds. Overall, this study highlights promising ABL1 inhibitors, laying the ground for further investigations.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803227","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

Multicomponent reaction synthesis and evaluation of novel 3,4-dihydropyrazine[1,2-b]Indazole-1(2H)-one derivatives as inhibitors of pyroptosis and inflammation. 新型3,4-二氢吡嗪[1,2-b]吲哚唑-1(2H)- 1衍生物的多组分反应合成及对焦亡和炎症抑制剂的评价。

IF 3.8 2区化学

Molecular Diversity Pub Date : 2025-08-09 DOI: 10.1007/s11030-025-11312-5

Zhen Dai, Donglin Yang, Ke Wang, Zhiping Chen, Jihong Tan, Yue Tian, DianYong Tang, Zhigang Xu, Zhongzhu Chen, Yong Li

{"title":"Multicomponent reaction synthesis and evaluation of novel 3,4-dihydropyrazine[1,2-b]Indazole-1(2H)-one derivatives as inhibitors of pyroptosis and inflammation.","authors":"Zhen Dai, Donglin Yang, Ke Wang, Zhiping Chen, Jihong Tan, Yue Tian, DianYong Tang, Zhigang Xu, Zhongzhu Chen, Yong Li","doi":"10.1007/s11030-025-11312-5","DOIUrl":"https://doi.org/10.1007/s11030-025-11312-5","url":null,"abstract":"Inflammation is a protective response by the body aimed at maintaining tissue homeostasis by eliminating pathogenic microbial infection, irritants, or tissue damage. However, dysregulated inflammation is pathological and involved in various diseases such as metabolic disorders, cancer, and neurodegenerative diseases. In this study, multicomponent reaction, an efficient tool for the synthesis of complex compounds with potential biological activities, was employed to synthesize twenty 3,4-dihydro-pyrazine[1,2-b]indazole-1(2H)-one derivatives and two 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one analogues. We next identified compounds 6e and 6r as potential inhibitors for NLRP3 inflammasome-driven pyroptosis through activity-based screening and investigated their potential binding modes with the NLRP3 protein via molecular docking. Further studies on anti-inflammatory activity showed that compounds 6e and 6r also significantly inhibited LPS-induced NO release, among which compound 6e had better anti-inflammatory activity, with an IC50 of 8.55 ± 0.32 μM in inhibiting NO release. Additionally, qPCR analysis indicated that compound 6e notably suppressed the gene transcription of the pro-inflammatory cytokine IL-6. In conclusion, this study identifies compound 6e, featuring a novel 3,4-dihydro-pyrazine[1,2-b]indazole-1(2H)-one scaffold, as a promising hit compound with inhibitory activity against pyroptosis and key inflammatory mediators. These findings highlight this chemotype as a valuable starting point for the development of a new class of anti-inflammatory agents.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803228","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