Molecular Diversity最新文献

{"title":"Molecularly diverse lonazolac-inspired pyrazole-cyanopyridin-2-one conjugates: design, synthesis, in vitro, in vivo and in silico studies as multi-target anti-inflammatory agents.","authors":"Marwa A Aziz, Azizah M Malebari, Tarek S Ibrahim, Mohamed F Radwan, Deiaa E Elsayed Abouzed, Rasha M Allam, Majed Alharbi, Ahdab N Khayyat, Gamal El-Din A Abuo-Rahma, Mamdouh F A Mohamed","doi":"10.1007/s11030-026-11558-7","DOIUrl":"10.1007/s11030-026-11558-7","url":null,"abstract":"<p><p>New pyrazole/3-cyanopyridin-2-one conjugates 4a-f and 5a-h were designed and synthesized; their anti-inflammatory activities were evaluated in vitro and in vivo. In the LPS-induced RAW 264.7 cell line, nitric oxide (NO) inhibitory activity revealed that 4b, 4e, and 5c were the most powerful NO inhibitors, with % inhibition of 64.97, 71.45 and 73.61, respectively, compared with indomethacin (60.97). Hybrids 4f (IC₅₀ = 2.64 µM) and 5e (IC₅₀ = 0.34 µM) were the most potent COX-2 inhibitors with selectivity indexes of 8.1 and 12.6, respectively, compared with Celecoxib (IC₅₀ = 1.33 µM, SI = 4.8), while 4e and 5c were the most potent 5-LOX inhibitors, with IC₅₀ values of 2.75 and 0.71 µM, respectively, compared to the zileuton (IC₅₀ = 0.45 µM). Treatment of carrageenan-induced paw inflammation rats, with hybrids 4b, 4e, 4f, 5c, and 5e resulted in outstanding anti-inflammatory activity with significant inhibition of paw inflammation, reduction in PGE2, and proinflammatory cytokines (TNF-α, and IL-1β levels). Moreover, the in vivo ulcerogenic study in rats suggested the safety of the tested hybrids when administered at high concentrations on gastric mucosa. Molecular docking using GNINA v1.3, validated by redocking against the native 3LN1-celecoxib and 6N2W-30Z complexes, together with molecular dynamics simulations, produced binding poses and interaction networks that are consistent with the recorded potency and selectivity, particularly for 5e in COX-2 and 5c in 5-LOX. In parallel, ligand-based 3D-QSAR (CoMFA/CoMSIA) and quantum-chemical descriptors established a coherent structure-activity relationship across the series and delineated the steric and electronic features governing anti-inflammatory activity. It could be preliminarily suggested that conjugates 4e and 5c could be considered as NO/5-LOX inhibitor, while conjugate 4f is a selective COX-2/5-LOX inhibitor, and 5e is a selective COX-2 inhibitor. These results indicate that 4e, 5c, and 4f are promising multitarget anti-inflammatory candidates that require further optimization.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8253-8276"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863359","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":"Electrochemical thioester synthesis enabled by phosphine promotion from carboxylic acids and disulfides.","authors":"Hong Zeng, Ming-Qiu-Hao Fu, Zhi Guan, Yan-Hong He","doi":"10.1007/s11030-026-11598-z","DOIUrl":"10.1007/s11030-026-11598-z","url":null,"abstract":"<p><p>Thioesters serve as important pharmacophores and synthetic intermediates, yet their conventional synthesis typically requires high temperatures, transition metal catalysts, or toxic and malodorous thiols. Herein, we present a simple and green electrochemical approach for the thioesterification of carboxylic acids with aromatic disulfides as direct sulfur surrogates, promoted by triphenylphosphine. The reaction proceeds under mild conditions without requiring transition metals, external reducing agents, or inert atmosphere. A broad scope of aromatic, aliphatic, and heterocyclic carboxylic acids, along with diversely substituted aromatic disulfides, are well tolerated, affording the corresponding thioesters in moderate to excellent yields. Gram‑scale synthesis and downstream derivatization demonstrate the practical utility of this protocol. Mechanistic studies support a radical-radical cross‑coupling pathway. This work offers a scalable and environmentally benign alternative for thioester synthesis.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8537-8545"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337462","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":"10.1007/s11030-026-11569-4","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8105-8118"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","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":"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":"10.1007/s11030-026-11498-2","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"7569-7582"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","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":"Naphthalene-based hydroxamate HDAC inhibitors with anti-breast tumor activity.","authors":"Hui Song, Feng-Chao Wang, Wan-Dong Liu, Quan-Hao Wei, Feifei Yang, Peipei Shan, Hua Zhang","doi":"10.1007/s11030-026-11607-1","DOIUrl":"10.1007/s11030-026-11607-1","url":null,"abstract":"<p><p>Histone deacetylases (HDACs) are attractive therapeutic targets due to their established role in tumorigenesis. In this study, a series of naphthalene-based hydroxamate derivatives were designed and synthesized as novel HDAC inhibitors. Among them, compound 6e showed excellent inhibitory activities against HDAC1 and 4T1 cancer cell line, and it also increased the levels of acetylated histones H3 and H4. Moreover, 6e induced significant cell apoptosis and cycle arrest. Importantly, 6e exhibited significant antitumor activity in the 4T1 orthotopic autograft mouse model. Collectively, these results identify the naphthalene-hydroxamate scaffold as a promising template for the development of novel HDAC-targeted anticancer agents.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"7441-7457"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051379","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":"10.1007/s11030-026-11543-0","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"7929-7952"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","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":"Correction to: 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/s11030-026-11599-y","DOIUrl":"10.1007/s11030-026-11599-y","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8177-8180"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203583","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, characterization and exploration of anti-HBV activity of matrine-adenine hybrids.","authors":"Meng-Fan Xie, Zhou-Fei Zheng, Jing-Lei Wang, Rong-Tao Li, Zhi-Jun Zhang","doi":"10.1007/s11030-026-11547-w","DOIUrl":"10.1007/s11030-026-11547-w","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"7907-7927"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662097","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":"Theoretical visualization of covalent and non-covalent interactions: molecular diversity and substituent effects governing the reactivity of Bulbophyllum bibenzyl derivatives.","authors":"Fatiha Guenfoud, Oussama Khaoua, Noura Benbellat","doi":"10.1007/s11030-026-11595-2","DOIUrl":"10.1007/s11030-026-11595-2","url":null,"abstract":"<p><p>Natural products from Bulbophyllum species were systematically investigated as potential antioxidant scaffolds using density functional theory, real-space topological analyses, pharmacokinetic and toxicity prediction, molecular docking, and 100 ns molecular dynamics simulations, in comparison with Quercetin and Resveratrol. Frontier molecular orbital analysis revealed relatively large HOMO-LUMO gaps for the derivatives (5.41-5.67 eV) compared to 3.97 eV for the reference compounds, indicating higher electronic stability. Muscatilin displayed the lowest hardness (2.70 eV) and highest softness (0.185 eV^-1), suggesting enhanced chemical reactivity. Real-space topological analyses (QTAIM, RDG/NCI, IRI, DORI, LOL, ELF) provide a molecular-level interpretation of interactions relevant to antioxidant behavior. In particular, Muscatilin exhibited a more favorable electron density distribution that may facilitate radical stabilization following hydrogen or electron transfer, thereby suggesting improved antioxidant potential. SwissADME profiling predicted favorable drug-likeness, high gastrointestinal absorption, and blood-brain barrier permeability for all compounds except Quercetin, while toxicity prediction showed high LD₅₀ values for Tristin, Muscatilin, and Gigantol (2260 mg/kg) with nephrotoxicity as a shared class and improved cardiac safety for Muscatilin and Gigantol. Molecular docking results suggested binding affinities ranging from - 7.2 to - 9.2 kcal/mol toward bovine superoxide dismutase (SOD), with Muscatilin showing the most favorable interaction. Molecular dynamics simulations further indicated stable ligand binding within the SOD active channel, supported by MM-GBSA binding energy estimates. Collectively, Muscatilin and Gigantol are predicted to exhibit promising activity-safety profiles and may serve as potential antioxidant lead compounds, warranting further experimental validation.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8423-8459"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051892","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":"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":"7891-7905"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","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}