Molecular Diversity最新文献

{"title":"Integrated LC-Orbitrap-MS and network pharmacology decipher the pharmacological basis of Eucommiae folium in treating rheumatoid arthritis.","authors":"Yasi Deng, Ling Liang, Haokai Lin, Xinyang Shen, Hao Zheng, Ying Deng, Xing Tian, Juan Huang, Ye Zhang, Bin Li, Huanghe Yu, Wei Wang","doi":"10.1007/s11030-026-11495-5","DOIUrl":"https://doi.org/10.1007/s11030-026-11495-5","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353269","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 biological evaluation of novel Kojic acid-cinnamic acid hybrids as tyrosinase inhibitors.","authors":"Yaxin Wen, Qingqing Yu, Fang Yang, Jianping Li, Ming Lang, Jia-Lei Yan, Xuetao Xu","doi":"10.1007/s11030-026-11487-5","DOIUrl":"https://doi.org/10.1007/s11030-026-11487-5","url":null,"abstract":"<p><p>Tyrosinase is the key rate limiting enzyme that controls melanin production. A series of novel kojic acid-cinnamic acid hybrids (JP1~26) were synthesized as tyrosinase inhibitors. All compounds displayed potential anti-tyrosinase activity with IC₅₀ values of 0.51~1.53 µM, ~ 10-30 folds stronger than control kojic acid. Among them, the strongest inhibitor JP5 inhibited tyrosinase in a mixed-type. Fluorescence quenching, 3D fluorescence, and CD spectra revealed the binding characteristic of JP5 with tyrosinase. Molecular docking displayed their binding detail with catalytic site residues. In addition, JP5 also could inhibit intracellular tyrosinase activity, thence, inhibiting melanin production in B16 cells. Therefore, kojic acid-cinnamic acid hybrids could service as potential tyrosinase inhibitors.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324090","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":"Orexin 2 receptor crosstalk with GLP1-R reveals dual therapy for improvement of sleep deprivation-induced obesity: an integrated network pharmacology, molecular docking and molecular dynamics simulation approach.","authors":"Vishal Chhabra, Shubham Singh Bartwal, Saqib Hameed, Nitesh Kumar","doi":"10.1007/s11030-026-11497-3","DOIUrl":"https://doi.org/10.1007/s11030-026-11497-3","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324147","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":"Exploring molecular frameworks for modulating NLRP3-driven neuroinflammation in Alzheimer's disease.","authors":"Chandrasekaran Sahana Reddy, Amarjith Thiyyar Kandy, Giridharan Sivakumar, Anand Vijayakumar","doi":"10.1007/s11030-026-11498-2","DOIUrl":"https://doi.org/10.1007/s11030-026-11498-2","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324105","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":"Advancement in peptide-based therapeutics for the treatment of type 2 diabetes mellitus: current progress and future prospects.","authors":"Md Fahim Shahriar, Janisa Kabir, Yi Kong","doi":"10.1007/s11030-025-11455-5","DOIUrl":"https://doi.org/10.1007/s11030-025-11455-5","url":null,"abstract":"<p><p>Diabetes is a chronic medical disorder caused by insufficient production of the hormone insulin by the pancreas. Although there are various treatment options available for controlling diabetes, including non-peptide-based medications, the majority of these have adverse effects and are limited in comparison to peptide-based drugs. Protein drugs offer numerous benefits, including weight loss, significant reductions in blood glucose levels, and an extremely low risk of hypoglycemia. This article discusses treatment modalities, presents existing therapies, provides an in-depth comparison of peptide-based and other drugs, examines current development and barriers, offers some recommendations, and outlines future research directions for peptide drugs in the treatment of T2DM. In recent days, several computational tools and AI models, including ESMFold, ProteinMPNN, Schrödinger, and AutoDock Vina, have played an essential role in peptide-based drug discovery. Therefore, this article also highlights the significance of AI drug discovery, diverse AI models, and other computational tools to enhance peptide-based drug discovery and development.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147288860","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":"Total synthesis of marine cyclopeptide largamides B and H, and tiglicamide B.","authors":"Youzhi Li, Yuzhao Chen, Shuo Liang, Shiwei Qu, Jia-Lei Yan, Tao Ye, Zhongliang Dai","doi":"10.1007/s11030-026-11488-4","DOIUrl":"https://doi.org/10.1007/s11030-026-11488-4","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281660","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":"Phthalazine scaffolds in medicinal chemistry: a review of their synthesis, versatility, and pharmacological significance.","authors":"Bharvi Lakkad, Riddham Hadavani, Vicky Jain, Yashwantsinh Jadeja","doi":"10.1007/s11030-026-11489-3","DOIUrl":"https://doi.org/10.1007/s11030-026-11489-3","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281641","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":"Integrative computational and experimental identification of marine bacterial acetylcholinesterase inhibitors against alzheimer's disease.","authors":"Mohammed H Alqarni, Talha Jawaid, Saif Ahmed, Aftab Alam","doi":"10.1007/s11030-026-11493-7","DOIUrl":"https://doi.org/10.1007/s11030-026-11493-7","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a powerful neurodegenerative disease characterized by cholinergic deficiency, where the inhibition of acetylcholinesterase (AChE) remains a clinically validated strategy. In our current work, a virtual screening platform supported by machine learning identified new inhibitors of AChE out of a structurally diverse collection of 2,895 marine bacterial natural products. Following a curation based on a structure-based strategy, a robust regression model was constructed from the physicochemical and structural characteristics of the reported inhibitors of AChE in an attempt to predict the inhibitory strength (pIC₅₀) of the top-scored ligands. The model had high predictive fidelity and led to the selection of twenty prospective candidates, out of which three (CMNPD25858, CMNPD28646, and CMNPD28412) were shortlisted according to activity profiles and drug-likeness filters. The shortlisted compounds were prepared for quantum-level refinement through density functional theory in order to improve electronic and structural precision. These optimised ligands were then evaluated under physiological conditions in terms of binding stability, conformational study, and intermolecular interaction through all-atom molecular dynamics simulation. CMNPD25858 demonstrated outstanding structural retention, stable persistent hydrogen bonding, and negligible displacement in the catalytic site. Principal component analysis and free energy landscape mapping revealed a highly confined, energetically favorable conformational basin. Structural overlays of post-simulation minima with initial docking poses confirmed minimal divergence. MM-GBSA free energy calculations substantiated the superior binding affinities of CMNPD25858 (-87.90 kcal/mol) and CMNPD28646 (-83.44 kcal/mol) relative to the reference compound. In vitro AChE inhibition assays revealed that compound CMNPD25858 demonstrated the highest inhibition (75%) at 1 mg/ml, followed by CMNPD28646 (64%) and CMNPD28412 (57.81%), consistent with in silico predictions when compared to the standard Donepezil (95.27%). Therefore, these integrative studies highlight the strategic utility of machine learning in accelerating structure-activity prediction and rational hit selection, and identifies marine-derived CMNPD25858 and CMNPD28646 as potent, dynamically stable AChE inhibitors with high potential for anti-Alzheimer's therapeutic development.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281662","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":"Structure-based computational investigation of potential TarA inhibitors in Staphylococcus aureus.","authors":"Boggarapu Ganesh, Lalitha Guruprasad","doi":"10.1007/s11030-026-11496-4","DOIUrl":"https://doi.org/10.1007/s11030-026-11496-4","url":null,"abstract":"<p><p>Staphylococcus aureus, a spherical Gram-positive bacterium commonly found to coinhabit humans, can also cause minor skin infections to life-threatening conditions such as pneumonia in individuals with weakened immune systems. The bacterium has developed resistance against conventional antibiotics. This underscores the urgent need for novel therapeutic strategies that act on the cell structure and therefore integrity of the bacterium. Wall teichoic acids (WTAs) are essential anionic glycopolymers covalently anchored to the peptidoglycan layer of Gram-positive bacteria, including S. aureus and are crucial for bacterial survival. The biosynthesis of WTA occurs by a multi-step process in the cytoplasm and proceeds through membrane translocation and incorporation into the cell wall. The earliest and most essential step in this pathway is catalyzed by TarA, which transfers N-acetylglucosamine (GlcNAc) to undecaprenyl phosphate, forming the WTA precursor lipid I. TarA catalyzes the reaction that serves as the first committed step in WTA biosynthesis, without which the entire WTA polymer cannot be constructed or transported. The TarA protein domain has emerged as a promising target for drug development due to its pivotal role in cell wall biosynthesis. We obtained the S. aureus TarA three-dimensional structure from AlphaFold2, performed virtual screening on diverse compound libraries so as to establish their binding to the target protein, which led to the identification of hit compounds with good binding affinity towards TarA domain and involvement of key amino acid residue interactions. This was followed by molecular docking studies, assessment of drug likeness properties of hit compounds and molecular dynamics (MD) simulations of S. aureus TarA-hit molecule complexes using Amber18 bio-simulations package. MD trajectory analysis; root mean square deviation, root mean square fluctuation, hydrogen bonding analysis, solvent accessible surface area, principal component analysis, secondary structure analysis, clustering analysis, free energy landscape, interactive hydrogen bond matrix, binding free energies of the simulated complexes and steered MD simulations were studied. This study resulted in the identification of new hit molecules with a potential to reduce the risk of the S. aureus infections.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281657","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":"Medicinal chemistry perspective of chalcone derivatives as anticancer agents: synthetic strategy, biological activity, and structure-activity relationship.","authors":"Aryadipto Dasgupta, R Rajesh, Pronoy Kanti Das, Gurubasavaraja Swamy Puravarga Matada, Prasad Sanjay Dhiwar, Arghya Paik","doi":"10.1007/s11030-025-11434-w","DOIUrl":"https://doi.org/10.1007/s11030-025-11434-w","url":null,"abstract":"<p><p>Chalcones are a subclass of flavonoids characterized by the presence of an α, β-unsaturated carbonyl system, and they have emerged as important scaffolds in medicinal chemistry because of their structural simplicity, ease of synthesis, and wide spectrum of pharmacological activities. They occur abundantly in nature and are reported to exhibit antioxidant, anti-inflammatory, antimicrobial, and particularly anticancer effects, making them attractive leads for therapeutic development. This review specifically highlights the most recent advances in chalcone-based anticancer research, with a focus on the structural features directly linked to enhanced cytotoxicity activity. Naturally occurring chalcones and their general pharmacological significance are briefly summarized to provide fundamental context. Classical methods, such as the Claisen-Schmidt condensation, remain the most widely used due to their simplicity and high yields, while modern catalytic, solvent-free, and green methodologies have expanded the diversity and efficiency of chalcone libraries. In parallel, structure-activity relationship (SAR) analyses are highlighted to illustrate how substituent effects, heterocyclic incorporation, and linker modifications influence activity profiles. Selected studies are discussed to demonstrate the relationship between structural design and cytotoxic responses across different cancer models. In the selected studies, aim to demonstrate how structural modifications can modulate cellular interactions, enhance therapeutic efficacy, and impact treatment outcomes across various cancer models. By integrating advances in synthesis with biological evaluation, this review emphasizes the versatility of chalcones and provides an updated framework for guiding rational design. The collective evidence underscores their promise as adaptable scaffolds for the development of next-generation anticancer agents.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281675","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}