Molecular Diversity最新文献

{"title":"In silico discovery of natural and synthetic inhibitors targeting AKT1 in prostate cancer.","authors":"Hemantha Mani Kumar Chakravarthi Chanda, Sudheer Kumar Katari","doi":"10.1007/s11030-026-11563-w","DOIUrl":"https://doi.org/10.1007/s11030-026-11563-w","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759347","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}

{"title":"AI-driven discovery of natural product-derived FAK1 inhibitors for idiopathic pulmonary fibrosis.","authors":"Xing-Yi Chen, Mei-Hong Lu, Bin Li, Ya Zhou, Li Liu, Hao Yang, Qiu-Yu Wang, Lin Chang, Yu-Lan Zhao, Dong-Mei Wang, Bin Li, Ben-Rong Mu","doi":"10.1007/s11030-026-11556-9","DOIUrl":"https://doi.org/10.1007/s11030-026-11556-9","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759262","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}

{"title":"Rational scaffold discovery for HIV-1 reverse transcriptase inhibitors via integrated in silico approaches.","authors":"Aakanksha Kunwar, Arzoo Rai, Suruchi Bhambri, Prakash C Jha","doi":"10.1007/s11030-026-11568-5","DOIUrl":"https://doi.org/10.1007/s11030-026-11568-5","url":null,"abstract":"<p><p>Human Immunodeficiency Virus-1 (HIV-1) Reverse Transcriptase (RT) remained an epicentre of therapeutic target, yet the efficacy of current non-nucleoside reverse transcriptase inhibitors (NNRTIs) is compromised by drug-induced liver toxicity. In this study, an integrated in silico approach combining similarity-based virtual screening, molecular docking, molecular dynamics, MM-PBSA, followed by molecular descriptor analysis, was employed to identify NNRTI scaffolds with improved safety and efficacy. The similarity-based virtual screening of ZINC and ChEMBL databases, followed by ADMET filtering, highlighted candidates with reduced predicted hepatotoxicity relative to FDA-approved NNRTIs. Among them, ZINC000066352010 exhibited a highly stable binding orientation within the NNRTI binding pocket, stabilized by hydrogen bonding with Lys101 and conserved hydrophobic contacts with Tyr181, Val179, and Trp229. Molecular Dynamics simulations provided compelling validation of this binding mode, as evidenced by the lowest ligand RMSD of 0.05 nm amongst the short-listed candidates, exhibited a persistent average number of hydrogen bonds of 1.95, and markedly reduced backbone fluctuations of RT relative to the apo-protein. These effects indicate enhanced conformational rigidity and long-term stability of the protein-ligand complex. The MM-PBSA provided quantitative thermodynamic support, with a binding energy of - 47.90 Kcal/mol, demonstrating stronger stabilization compared to the reference inhibitor (i.e., 9PJ). The enhanced affinity was driven predominantly by stable Van-der Waals interactions and minimized desolvation penalties. Frontier Molecular Orbital (FMO) and global reactivity descriptor analyses revealed an optimal HOMO-LUMO gap of 0.156 eV and an electrophilicity index of 0.14 eV, positioning it electronically within the window of FDA-approved NNRTIs, thereby indicating balanced reactivity and optimal electronic stability. Complementary electrostatic potential mapping highlighted well-defined reactive centres corroborative to the biomolecular target. Collectively, these findings positioned ZINC000066352010 as a promising NNRTI candidate with improved predicted safety and electronic stability parallel to an FDA-approved drug.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759338","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}

{"title":"Novel organophosphorus-quinolone hybrids as potential antimicrobial agents: design, synthesis, biological evaluation, and in vivo antibacterial effect in bacteria-infected zebrafish model.","authors":"Liangliang Wang, Jie Chen, Yan Liu, Xuemin Xian, Haitao Zhang","doi":"10.1007/s11030-026-11541-2","DOIUrl":"https://doi.org/10.1007/s11030-026-11541-2","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759351","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}

{"title":"Synthesis of structurally diverse thiazole-fused indole derivatives via a one-pot four-component cascade reaction.","authors":"Guanghua Wei, Qi Zhang, Chunmei Li, Furen Zhang","doi":"10.1007/s11030-026-11569-4","DOIUrl":"https://doi.org/10.1007/s11030-026-11569-4","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759301","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}

{"title":"Synthesis and molecular characterization of a novel FA-ADH-GMS conjugated pH-responsive lipid for targeted drug delivery.","authors":"Sai Ramya Bodagala, Prasanthi Samathoti","doi":"10.1007/s11030-026-11562-x","DOIUrl":"https://doi.org/10.1007/s11030-026-11562-x","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759315","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}

{"title":"TripleBind: a generalizable deep learning framework for protein-nucleic acid and protein-ligand binding sites prediction based on pre-trained protein language models.","authors":"Zhiwei Liu, Ruisheng Zhang","doi":"10.1007/s11030-026-11557-8","DOIUrl":"https://doi.org/10.1007/s11030-026-11557-8","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759307","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}

{"title":"Quinazoline-sulfonamide hybrids as multitarget anticancer agents: inhibition of carbonic anhydrase IX/XII isoforms and VEGFR-2 with in vitro and in silico validation.","authors":"Mohamed A Zeidan, Mohammad M Al-Sanea, Mohamed R Elnagar, Mohamed M Tawfik, Hamed W El-Shafey, Samar S Tawfik, Simone Brogi, Abdelrahman Hamdi","doi":"10.1007/s11030-026-11543-0","DOIUrl":"https://doi.org/10.1007/s11030-026-11543-0","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721434","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}

{"title":"Multi-omics, molecular modeling and experimental analysis of carcinogen benzo(a)pyrene promoting the progression of laryngeal cancer.","authors":"Yifan Hu, Zhizhen He, Xiuping Yang, Baoai Han, Xiong Chen","doi":"10.1007/s11030-026-11548-9","DOIUrl":"https://doi.org/10.1007/s11030-026-11548-9","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721391","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}

{"title":"A label-free cell-based screening identifies enhydrin as a novel natural antagonist of the histamine H1 receptor.","authors":"Ziwei Zhang, Qichao Hu, Hanzhen Wang, Zhichao Zhou, Zhan Si, Liying Shi","doi":"10.1007/s11030-026-11549-8","DOIUrl":"https://doi.org/10.1007/s11030-026-11549-8","url":null,"abstract":"<p><p>Histamine H1 receptor antagonists are widely used to treat allergic conditions. As some synthetic drugs in this class are associated with adverse effects, discovering new antagonists from natural sources remains an active pursuit. Efficient screening methods that evaluate receptor function in a physiologically relevant, integrated manner are still needed. In this study, we developed a label-free, cell-based assay to screen for H1 receptor antagonists by monitoring dynamic mass redistribution (DMR) in A431 cells, which endogenously express H1 receptor. After validating the system with reference agonists and antagonists, we screened a panel of 32 natural compounds and identified four initial hits, including the sesquiterpene lactone enhydrin. Enhydrin dose-dependently antagonize‌d histamine-induced DMR responses and downstream p38 MAPK (mitogen-activated protein kinase) phosphorylation, and it prevented agonist-triggered internalization of the H1 receptor. Molecular docking and dynamics simulations supported a direct mechanism, showing that enhydrin forms a stable complex within the receptor binding pocket through sustained interactions with residues including LYS191, ASN198, and TRP428. Our findings establish enhydrin as a promising therapeutic candidate for allergic inflammatory responses by antagonizing the H1 receptor. This study extends the label-free cell-based screening of H1 receptor antagonists, thereby facilitating the discovery of novel anti-allergic agents.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662112","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}