Molecular Diversity最新文献

{"title":"Structural insights into TNF-α inhibition by bioactive compounds found in plants of North East India: in vitro validation and in silico investigations using QSAR, molecular docking, and dynamics simulations.","authors":"Sarbani Dey Ray, Supratim Ray, Bibhas Pandit, Subham Ghosh, Anjali Murmu, Partha Pratim Roy, Jagadish Singh","doi":"10.1007/s11030-026-11574-7","DOIUrl":"https://doi.org/10.1007/s11030-026-11574-7","url":null,"abstract":"<p><p>Medicinal plants from the Eastern Himalayas of Northeast India are integral to traditional therapies for inflammation. This study evaluated the anti-inflammatory potential of 23 reported phytochemicals isolated from this region by targeting TNF-α, a critical mediator of autoimmune disorders. TNF-α production was induced in human peripheral blood mononuclear cells using 100 ng/mL lipopolysaccharide for 24 h and quantified using ELISA. The IC₅₀ was calculated by probit regression, with methotrexate as the reference standard (IC₅₀ = 1.96 µM; 94% inhibition at 3.5 µM). Rutin emerged as the most potent inhibitor (IC₅₀ = 2.15 µM; 93% inhibition at 4 µM), followed by myricitrin and quercetin-3-O-glucoside (IC₅₀ < 10 µM). Conversely, anthocyanins and punicic acid were the least effective (> 300 µM). QSAR modelling indicated that bioactivity correlates with small, planar, polyhydroxylated structures, specifically 3-O-glycosylated flavonols and ellagitannin-like polyphenols, whereas steric bulk in larger molecules diminished efficacy. Molecular docking against TNF-α (PDB: 2AZ5; Glide XP) revealed strong binding affinities for rutin (- 10.352 kcal/mol), myricitrin (- 10.020 kcal/mol), and quercetin-3-O-glucoside (- 10.011 kcal/mol), driven by hydrogen bonding (TYR151, SER60, LEU120, and GLY121) and π-π stacking (TYR119). However, 100 ns Molecular Dynamics simulations and MM-GBSA analyses identified myricitrin as the most thermodynamically stable complex, characterized by tight pocket occupancy, sustained hydrogen bonding, and reduced RMSD fluctuations. Taken together, these results imply that rutin and myricitrin are promising scaffolds for the development of anti-inflammatory drugs.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832216","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":"Retraction Note: A new Cu(II)-containing coordination polymer: protective effect and mechanism exploration on elderly osteoporotic hip fractures via regulating the wnt signaling pathway.","authors":"Kai Yu, Jie Yang, Shangding Xie, Bingqin Ma, Liangzhi Wang","doi":"10.1007/s11030-026-11581-8","DOIUrl":"https://doi.org/10.1007/s11030-026-11581-8","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832095","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":"Integrated in vitro and in silico evaluation of rutin as a potential modulator of wound healing pathways.","authors":"Ghanshyam Parmar, Jay Mukesh Chudasama, Ashish Shah, Chintan Aundhia, Ashish Patel, Damiki Laloo, Ravi Bansal","doi":"10.1007/s11030-026-11572-9","DOIUrl":"https://doi.org/10.1007/s11030-026-11572-9","url":null,"abstract":"<p><p>Wound healing is a multifactorial biological process that requires the coordinated regulation of inflammation, cell migration, angiogenesis, growth, and extracellular matrix remodeling. These drawbacks of existing wound care treatments prompt the need to seek safe and cost-effective agents and multi-target agents. This was demonstrated in a study that investigated the wound-healing capacity of a natural flavonoid glycoside, rutin, using an integrated in vitro-in silico methodology. An MTT assay was used to determine the cytocompatibility of rutin in L929 fibroblast cells, and the results showed that cell viability was high at a wide range of concentrations. A scratch wound healing assay showed enhanced fibroblast migration and wound closure in a concentration-dependent manner, and wound contraction was nearly complete within 72 h at optimum concentrations. To understand the molecular mechanisms underlying these effects, network pharmacological analysis revealed 94 common targets between rutin-associated wound healing and rutin-associated genes. Protein-protein interaction analysis identified key regulatory nodes, such as PIK3R1, PRKCA, and EGFR, which are central to the pathways that regulate cell proliferation, migration, angiogenesis, and inflammatory regulation. Enrichment analysis of gene ontology and KEGG pathways revealed that the PI3K-Akt, MAPK, VEGF, and AGE-RAGE signaling pathways were highly involved. Molecular docking showed good binding affinities of rutin to PIK3R1, PRKCA, and EGFR, which was also confirmed by 100 ns molecular dynamics simulations that revealed complex stability and favorable conformational behavior. Density functional theory analysis showed that the electronic characteristics were in line with the antioxidant activity and the strong intermolecular interactions. Together, these results demonstrate that rutin is a promising multifunctional topical wound-healing agent and provide mechanistic evidence for its use in topical therapeutic applications.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832099","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":"Chemistry, pharmacology and spotlight on the clinical trials of remibrutinib: a first in class, oral Bruton's tyrosine kinase (BTK) inhibitor for chronic spontaneous urticaria.","authors":"Shah Alam Khan, Abdul Qadir, Aqsa Khan, Simran Kour, Asif Husain","doi":"10.1007/s11030-026-11577-4","DOIUrl":"https://doi.org/10.1007/s11030-026-11577-4","url":null,"abstract":"<p><p>Remibrutinib (Rhapsido^®), is an innovative oral Bruton's tyrosine kinase (BTK) inhibitor discovered and developed by Novartis for the treatment of chronic spontaneous urticaria (CSU), an autoimmune disease. It is a covalent, irreversible inhibitor that targets BTK, a key signalling node in the FcεRI pathway of mast cells and basophils, thereby suppressing the release of histamine and other inflammatory mediators. In September 2025, remibrutinib received its first US FDA approval for the treatment of CSU for adult patients who remain symptomatic despite H1 antihistamine treatment. This approval marks a significant advancement in CSU care that targets mast cell and basophil activation, two key contributors involved in hive formation and itching. This article reviews the development journey, scientific rationale, chemistry, pharmacological properties (pharmacokinetic, pharmacodynamics and safety profile), clinical trials, and granted patents that led to first FDA approval of an oral treatment for adult patients with CSU.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832102","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":"The architecture of computational antiviralism: a multi-scale framework from molecular targeting to viral ecosystem engineering.","authors":"Ahmed I Foudah, Mohammed H Alqarni, Akil Ahmad, Aftab Alam","doi":"10.1007/s11030-026-11553-y","DOIUrl":"https://doi.org/10.1007/s11030-026-11553-y","url":null,"abstract":"<p><p>The recurrent outbreak of viral pathogens and the possibility of the new pandemics demand the transition to the predictive and integrative computational frameworks instead of reactive one. This review describes computational antiviralism as an integrated approach that uses artificial intelligence (AI), virtual screening, and molecular design tools to identify antiviral targets at the molecular level. We compare deep learning-based structure models with physics-based molecular dynamics (MD) with network pharmacology to describe virus-host interactome dynamics. We also evaluate systems virology strategies that combine the transcriptomic, proteomic, and metabolomic data in order to solve infection-induced cellular reprogramming. The framework is not confined to the molecular, but includes evolutionary phylogenomics, epidemiological modelling of the zoonotic spillover, and climate-guided forecasting of cross-species transmission of viruses. We consider such key issues as assay heterogeneity, interpretability of models, and management of autonomous laboratory systems. Importantly, we explicitly acknowledge that no true end-to-end validated multi-scale antiviral pipeline currently exists; the framework is presented as a forward-looking research agenda with clearly defined open challenges. Collectively, this synthesis will bring computational antiviralism as an anticipatory field of study that can catalyze the broad-spectrum antiviral discovery, as well as providing preemptive countermeasures to emergent viral challenges through coordinated molecular, cellular and ecosystem-level interventions.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809469","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":"Deep learning architectures achieve state-of-the-art (SOTA) accuracy in protein secondary structure prediction.","authors":"Zahra Nikfarjam, Majid Jafari, Farshid Zargari","doi":"10.1007/s11030-026-11570-x","DOIUrl":"https://doi.org/10.1007/s11030-026-11570-x","url":null,"abstract":"<p><p>Protein secondary structure prediction represents an important intermediate step between a protein's linear amino acid sequence and its three-dimensional structure, with broad implications for synthetic biology, drug development, and disease research. Although experimental techniques such as X-ray crystallography provide highly accurate structural information, they are labor-intensive, time-consuming, and costly, which has motivated the development of computational alternatives. Early machine-learning approaches to this problem were limited in their ability to capture complex sequence-structure relationships. The introduction of convolutional and recurrent neural networks improved hierarchical feature extraction, and predictive performance advanced further with transformer-based architectures such as AlphaFold2. This review outlines recent advances in hybrid model design, benchmark datasets, and evaluation metrics for protein secondary structure prediction. We also discuss current methodological limitations, including data dependency and dataset bias, and outline future directions such as cross-species validation, uncertainty-aware modeling, and the still-emerging potential of incorporating heterogeneous biological data into next-generation PSSP frameworks.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809409","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":"Integrating AI into next-generation PROTAC Engineering: a comprehensive toolkit for rational PROTAC design.","authors":"Pitam Ghosh, Ryena Dhir, Dinki Sharma, Vivek Asati","doi":"10.1007/s11030-026-11567-6","DOIUrl":"https://doi.org/10.1007/s11030-026-11567-6","url":null,"abstract":"<p><p>PROTACs, also called proximity-inducing agents, are chimeric molecules composed of a ligand for protein of interest (POI), an E3 ligase ligand and a linker connecting them. PROTACs have transformed the therapeutic landscape by enabling an event-driven strategy to degrade disease-associated proteins previously regarded as undruggable. The unique event-driven mechanism of PROTACs allows selective protein degradation with greater potency and lower drug resistance than conventional occupancy-based inhibitors. Despite their advantages, challenges such as high molecular weight, low permeability, poor pharmacokinetic properties restrict their clinical applications. To overcome these limitations, AI-driven technologies are being utilised to generate novel, chemically valid PROTACs. This review highlights the drawbacks of conventional computational methods and explores emerging AI-driven tools applied to multiple areas of PROTAC research, such as target (POI) selection (DeepUSI, DrugnomeAI), linker generation (AIMLinker, DiffLinker), activity prediction (AI-DPAPT, DeepPROTAC), POI degradability assessment (PrePROTAC, MAPD), ternary complex modelling (ProFlow), PROTAC generation (PROTAC-RL), and ADME property estimation (MT-GNN). It also outlines current challenges such as data scarcity, reproducibility issues, inadequate model generalizability, emphasizing the need for hybrid models or integrated AI techniques to mitigate these limitations.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809344","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":"Design, synthesis, in silico and in vitro anti-breast cancer evaluation of novel indole-isoxazole/isoxazoline hybrids as ERα inhibitors.","authors":"Agnidipta Das, Vishakha, Tushar Midha, Mayank, Somesh Baranwal, Bhim Singh, Akhilesh Gangwar, Vikas Jaitak","doi":"10.1007/s11030-026-11565-8","DOIUrl":"https://doi.org/10.1007/s11030-026-11565-8","url":null,"abstract":"<p><p>Breast cancer (BC) remains the foremost cause of cancer mortality in women, with ER + subtypes accounting for over 70% of cases. Disease progression is driven by aberrant receptor signaling, marked by elevated ERα and diminished ERβ expression, underscoring the urgency of potent and targeted ERα inhibitors. Although selective estrogen receptor modulators like tamoxifen have significantly improved patient survival, their clinical utility is constrained by adverse effects like endometrial carcinoma, blood clot formation, deep vein thrombosis, hot flashes and VTE, alongside emergence of drug resistance. To overcome current limitations in ERα targeted therapy, we designed and synthesized a novel series of indole-conjugated isoxazole/ isoxazoline hybrids through a streamlined five-step synthetic route, affording moderate to high yields (70-90%). These hybrids were systematically evaluated against ERα-predominant and triple-negative BC cell lines, with promising candidates subjected to healthy cell cytotoxicity, receptor inhibition assays and comprehensive in silico validation. Among the synthesized hybrids, C04 and C06 emerged as lead candidates, demonstrating markedly superior anti-proliferative activity on ERα dominant BC cells compare to tamoxifen and bazedoxifene. Cell cycle arrest and apoptotic studies further confirmed capability of both compounds in apoptosis induction primarily through G0/G1 cell-cycle arrest. ERα inhibition assays highlighted the exceptional potency of C06, exceeding bazedoxifene by 3.3-fold and tamoxifen by 7.9-fold. C04 was identified with broad safety profile in HEK cell cytotoxicity studies. Molecular docking and dynamic simulations further validated their robust target engagement. Collectively, these findings established C04 and C06 as optimistic ERα targeted leads with superior efficacy and safety profiles than standard drug candidates.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809347","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":"Phytochemical targeting of SASP2-mediated DNA protection to impair spore resilience in Bacillus cereus: A Computational Investigation.","authors":"Rajaram Abhirami, Chandrabose Selvaraj, Sanjeev Kumar Singh","doi":"10.1007/s11030-026-11538-x","DOIUrl":"https://doi.org/10.1007/s11030-026-11538-x","url":null,"abstract":"<p><p>Spore-forming bacteria such as Bacillus cereus pose a significant public health challenge due to their ability to survive harsh environmental conditions, resist conventional decontamination strategies, and cause recurrent infections in clinical and food-associated environments. This persistence is primarily associated with sporulation, a tightly regulated developmental process in which long-term survival depends on maintaining genome integrity while cellular metabolism remains largely inactive. DNA-binding proteins are therefore central to sporulation, as effective DNA condensation and protection are essential for sporulation progression and cyst wall maturation. Among these, α/β-class small acid-soluble proteins (SASPs), particularly SASP2, bind to the DNA minor groove and stabilize the genome during dormancy. In this study, a structural model of the B. cereus SASP2-DNA complex was constructed and analyzed through an integrated computational approach to identify compounds targeting this interaction. Phytochemicals derived from Garcinia mangostana, Garcinia cowa, Ficus exasperata, and Entada abyssinica, previously reported for antimicrobial activity, were evaluated for their potential to interact with the SASP2-DNA interface, a mechanism not previously explored. Several compounds showed strong binding affinity at the SASP2-DNA minor-groove interface and were predicted to influence key interactions under simulated stress conditions, leading to DNA compaction stability and stress tolerance, which may subsequently affect cyst wall formation and spore viability. Notably, the identification of plant-derived compounds capable of targeting the SASP2-DNA interface represents a novel observation. Overall, these findings provide a promising computational basis for exploring strategies to limit the persistence and transmission of B. cereus infections.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809416","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":"Improving aptamer binding affinity for HN protein of newcastle disease virus: molecular dynamics simulations and MM/GBSA calculations studies.","authors":"Shuang Jiang, Xu Wen, Xiaoling Zheng, Xue Wang, Xianlu Lei, Yong Xie, Tao Le","doi":"10.1007/s11030-026-11573-8","DOIUrl":"https://doi.org/10.1007/s11030-026-11573-8","url":null,"abstract":"<p><p>Aptamers, as single-stranded DNA (ssDNA) or RNA oligonucleotides, are pivotal in biosensing due to their high affinity. However, excessive lengths of these nucleic acid probes can impair their binding affinity and target recognition efficiency. Traditional optimization methods, such as static structural modeling, fail to capture the dynamic interactions between aptamers and biological macromolecules. Therefore, optimizing aptamer length to enhance affinity while maintaining effective target recognition is crucial. Here, we employed 600ns molecular dynamics (MD) simulations using the amberff14sb and parmbsc1 force fields, alongside molecular mechanics/generalized Born surface area (MM/GBSA) free energy calculations to optimize the binding affinity of a ssDNA aptamer targeting the hemagglutinin-neuraminidase (HN) protein-a critical surface receptor of Newcastle disease virus (NDV) responsible for viral attachment and entry. By systematically truncating the aptamer sequence guided by normalized criteria to eliminate length bias, we identified a 10-nucleotide variant (fqh-2) that exhibited a hydrogen bond efficiency ratio (HBER) of 1.055 and a binding free energy efficiency ratio (BFEER) of -5.124 kcal/mol, reflecting enhanced interactions with the HN protein. Furthermore, a graphene oxide (GO)-based fluorescence quenching assay confirmed a threefold increase in binding affinity for the optimized aptamer, aligning with computational predictions. This study not only provides a dynamic structure-guided framework for aptamer optimization but also lays a theoretical foundation for further advancements in optimizing and tailoring aptamers for specific applications.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809341","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}