Molecular Diversity最新文献

{"title":"CPA-catalyzed enantioselective synthesis of α,α-bisindoles-assembled triarylmethanes between 3-indolyl[1,4]thiazepines and indoles via ring-opening/friedel-crafts reaction.","authors":"Teng Liu, Airong She, Fei Wang, Kaiquan Liu, Feixiang Cheng","doi":"10.1007/s11030-026-11617-z","DOIUrl":"10.1007/s11030-026-11617-z","url":null,"abstract":"<p><p>We describe that a type of new and flexible 3-indolyl[1,4]thiazepines can be efficiently merged with substituted indoles catalyzed by chiral phosphoric acid (CPA), providing a range of structurally diverse α,α-bisindoles-assembled triarylmethanes in excellent diastereomeric and enantiomeric excess (up to 92% de, > 99% ee), excellent yields, and 100% atom economy. These reactions harness the ability of 3-indolyl[1,4]thiazepines to form active species via a ring-opening process involving the cleavage of C-N bond that are subsequently trapped by nucleophilic indoles via Friedel-Crafts reaction. The late-stage modification, and identification of partial products exhibiting good anticancer activities highlights the utility of this methodology.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"7467-7474"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148209779","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":"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":"8087-8104"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","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":"Design, synthesis, anticancer estimation, and computational studies of novel benzochromenoimidazopyrimidines as CDK-2 inhibitors and apoptosis stimulators.","authors":"Fatma G Abdulrahman, Marwa T Sarg, Yasmin S Sheta, Eman S Nossier, Ebtehal M Husseiny","doi":"10.1007/s11030-026-11578-3","DOIUrl":"10.1007/s11030-026-11578-3","url":null,"abstract":"<p><p>Adopting both molecular hybridization and substituent variation strategies, a novel set of benzochromenoimidazopyrimidines with expected cyclin-dependent kinase 2 (CDK-2) inhibition potential was designed and synthesized. The NCI evaluated all novel hybrids in the 60 cell line panel, where five derivatives 6b, 6d, 6e, 6f, and 6 g showed superior activity. The most active hybrids were assessed for the five-dose cytotoxicity toward the most sensitive NCI cancer cells EKVX, UACC-62, and HS 578 T in addition to healthy cells (WI-38). Among the tested analogs, 6e, 6f, and 6 g exerted promising cytotoxicity toward HS 578 T cells where compound 6f exhibited significant antiproliferative activity with an IC₅₀ of 3.06 µM, exceeding that of Lapatinib by 7.6 fold. It also displayed a superior selectivity index (8.49) toward HS 578 T cells that is greater than that of Lapatinib by 7.08 fold. Additional tests have been done on these hybrids to ascertain their precise mechanism of action. Hence, CDK-2 inhibition, apoptosis assay, and cell cycle analysis for the superior analogs were estimated. The findings illustrated that analog 6f exerted the most potent CDK-2 inhibition with an IC₅₀ equal to 0.277 µM, which is approximately threefold the activity of Roscovitine (0.833 µM). As well, compound 6f arrested HS 578 T cell cycle at both S and G2/M phases and stimulated apoptosis by increasing Bax and Caspase-3 expression with a concurrent decline in the expression of Bcl-2. Additionally, ADMET prediction and the binding interaction of the most active derivatives with CDK-2 have been studied in silico to evaluate their potential as important antitumor agents.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8335-8354"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969581","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":"Differential response of HER2 - and HER2 + breast cancer cells to quinazoline and triazole derivatives: advancing receptor subtype-specific phytochemical targeting.","authors":"Jitender Singh, Pramod K Avti, Krishan L Khanduja, Divya Dahiya","doi":"10.1007/s11030-026-11561-y","DOIUrl":"10.1007/s11030-026-11561-y","url":null,"abstract":"<p><p>The current targeted therapies have limitations in treating HER2 - and HER2 + breast cancer subtypes, and investigating molecular pathways offers new avenues for effective treatment strategies. This study integrates the computational and biological assays to evaluate the differential anticancer potential of Quinazoline and Triazole derivatives for receptor-specific (HER2- and HER2 +) mechanisms in breast cancer. The predicted binding energies and interaction profiles, obtained from molecular docking and dynamic simulation studies, suggested distinct affinity patterns: F0922-0471 (ER > PR > HER2) and F2865-0609 (HER2 > ER = PR). Furthermore, these compounds exhibit receptor-ligand interaction patterns similar to those of FDA-approved drugs. ADMET profiling revealed the favorable drug-like properties and low toxicity, suggesting a non-carcinogenic and acceptable safety profile. In vitro studies demonstrated that both compounds caused significant cell death in HER2 - (MCF-7) and HER2 + (SKBR3) breast cancer cells, though through distinct cell cycle and ROS responses. The HER2 - cells showed a greater reduction in ER expression with the quinazoline derivative (F0922-0471) than with the triazole derivative, which significantly reduced HER2 expression in HER2 + cells, underscoring their receptor-specific effects. This study concludes that Quinazoline (F0922-0471) and Triazole derivatives (F2865-0609) show potential as receptor-specific, multi-targeted anticancer agents for distinct breast cancer subtypes, warranting further preclinical and clinical evaluations.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8277-8296"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863394","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, radiolabelling and preliminary evaluation of [⁶⁸Ga]Ga-DOTA-linked cyanuric chloride-glu-ureido scaffold for PSMA PET imaging.","authors":"Mohd Faheem, Vaibhav Pandey, Anjali Pal, Pradeep Kumar Sharma, Manisha Prasad, Manish Dixit","doi":"10.1007/s11030-026-11540-3","DOIUrl":"10.1007/s11030-026-11540-3","url":null,"abstract":"<p><p>Cyanuric chloride is a highly reactive, widely recognized compound in medicinal chemistry, enabling rapid and selective nucleophilic substitution reactions at its three chlorine positions. In the present study, explore the structural advantages of cyanuric chloride to develop a new DOTA-linked triazine-based scaffold for PSMA. Two scaffolds, abbreviated as PSMA-C1D and PSMA-C2D, were successfully synthesized with good yields and evaluated their properties through molecular docking, in vitro studies, radiolabelling, physicochemical properties, and internalization studies. The initial screening revealed that, the PSMA-C1D had greater potential as a PSMA-targeted imaging agent than PSMA-C2D. In vitro cytotoxicity assays further indicated good biocompatibility at imaging-relevant concentrations. The molecular docking demonstrated strong site-specific binding of PSMA-C1D to the PSMA active pocket (ΔG = - 10.2 kcal/mol), with interactions closely resembling the co-crystallized ligand. The radiolabelling of PSMA-C1D with Ga-68 shows high yield with > 95% radiochemical purity, excellent stability in multiple biological media, and high apparent molar activity (508 GBq/µmol). The tracer shows hydrophilicity (logD_7.4 = - 2.76 ± 0.02), low %PPB (18 ± 5.4), and has a nanomolar affinity (K_d = 0.38 nM), with the percentage of bound internalization in LNCaP cells was 15 ± 2.9% incubation for 1 h. The study highlights the value of cyanuric chloride as a modular chemical hub for the design and linking of radiopharmaceuticals. It identifies [⁶⁸Ga]Ga-PSMA-C1D as a promising, efficiently synthesizable, and highly PSMA-specific PET radiotracer for imaging prostate cancer.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"8119-8134"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809413","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":"BACE-1 inhibitors as potential drug candidates for treatment of Alzheimer's disease: a systematic review.","authors":"Navneet Kaur, Saurabh Gupta, Gulshan Bansal, Yogita Bansal","doi":"10.1007/s11030-026-11546-x","DOIUrl":"10.1007/s11030-026-11546-x","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"7583-7621"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662080","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":"TCM-based natural products in type 2 diabetes: a comprehensive review of bioactive compounds and molecular mechanisms.","authors":"Yifeng Ge, Yanzhong Zhang, Shuo Liu, Ruilun Chen, Hongyan Xiang, Feiyan Wu","doi":"10.1007/s11030-026-11608-0","DOIUrl":"10.1007/s11030-026-11608-0","url":null,"abstract":"<p><p>Type 2 Diabetes Mellitus (T2DM) is a complex metabolic disorder. It is marked not just by high blood sugar levels but also by insulin resistance, oxidative stress, chronic inflammation, issues with lipids, problems in mitochondria, and ongoing injury to β-cells. Because of this varied set of causes, natural products from Traditional Chinese Medicine (TCM) have gained interest as potential treatments that target multiple areas. This review compares three major TCM-derived classes of plant chemicals that have strong evidence supporting their effectiveness against diabetes: the alkaloid berberine, the polyphenol curcumin, and the saponin ginsenosides. We conducted a structured narrative review using databases like PubMed/MEDLINE, Web of Science, ScienceDirect, Scopus, Google Scholar, and CNKI. We focused on mechanistic in vitro studies, animal experiments, clinical evidence, and practical relevance. The evidence indicates that these compounds help regulate glucose and lipid levels through both common and unique mechanisms. Berberine is mainly linked to activating AMP-activated protein kinase, promoting glucose transport, reducing liver glucose production, and changing gut bacteria. Curcumin shows anti-inflammatory, antioxidant, anti-fibrotic, and protective effects, involving pathways like nuclear factor kappa B, c-Jun N-terminal kinase, transforming growth factor beta/Smad, and protein kinase B/glycogen synthase kinase-3 beta. Ginsenosides are more associated with insulin signaling through phosphoinositide 3-kinase/protein kinase B, protecting β-cells, and reducing kidney damage, while also affecting gut bacteria. Despite strong support from mechanistic and preclinical studies, wider clinical use is limited by issues like poor absorption, differences in formulations, varying doses, and inconsistent human studies. Overall, these compounds should be seen as promising additional treatments for T2DM, rather than primary therapies. Future advancements will hinge on better drug absorption, consistent formulations, and larger long-term clinical trials.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"7795-7809"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154823","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":"10.1007/s11030-026-11557-8","url":null,"abstract":"","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"7953-7965"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","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":"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":"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":"8181-8198"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","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":"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":"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":"8199-8223"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","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}