Archiv der Pharmazie最新文献

{"title":"Design and Synthesis of Ketoconazole Derivatives as Innovative Anti-Infective Agents","authors":"Gioele Renzi,&nbsp;Andrea Angeli,&nbsp;Silvia Selleri,&nbsp;Costanza Spadini,&nbsp;Nicolo’ Mezzasalma,&nbsp;Marcus T. Hull,&nbsp;Steven L. Kelly,&nbsp;Clemente Capasso,&nbsp;Clotilde S. Cabassi,&nbsp;Fabrizio Carta,&nbsp;Claudiu T. Supuran","doi":"10.1002/ardp.70062","DOIUrl":"https://doi.org/10.1002/ardp.70062","url":null,"abstract":"<p>A novel series of compounds was designed and synthesized by combining the distal piperazine nitrogen of the antifungal ketoconazole (KTZ) with primary arylsulfonamides. The aim of this study is to present the basis for a new generation of <i>Malassezia</i> antifungal agents able to inhibit the enzyme lanosterol-14α-demethylase (CYP51; EC 1.14.13.70) as well as a newly emergent therapeutic target: carbonic anhydrases (CAs; EC 4.2.1.1). The final compounds showed effective interactions with the intended targets in vitro, as well as KTZ comparable minimum inhibitory concentrations on yeast strains of the <i>Malassezia</i> genus: <i>Malassezia furfur</i> ATCC 14521; <i>Malassezia globosa</i> ATCC MYA 4612; and <i>Malassezia pachydermatis</i> DSM 6172. Overall, the data obtained account for the reported compounds as promising antifungal candidates with high safety profiles for the management of fungal infections.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promising Antimycobacterial Agents: Salicylidenehydrazines","authors":"Oya Unsal Tan,&nbsp;Sıva Krıshna Vagolu,&nbsp;Tone Tønjum,&nbsp;Ozan Kaplan,&nbsp;Rahime Simsek","doi":"10.1002/ardp.70065","DOIUrl":"https://doi.org/10.1002/ardp.70065","url":null,"abstract":"<div>\u0000 \u0000 <p>Tuberculosis (TB) remains a major global health challenge, underscoring the urgent need for new therapeutic options. In this study, a series of salicylidenehydrazine derivatives were synthesized and characterized using spectroscopic techniques. Their antimycobacterial activity was assessed against <i>Mycobacterium tuberculosis</i> H37Rv. Among the 35 synthesized compounds, nine demonstrated significant inhibitory activity, with MIC values ranging from 0.78 to 50 μM. These active molecules were further evaluated against clinical isoniazid-resistant (bearing <i>inhA</i> promoter and/or <i>katG</i> mutations) and multidrug-resistant (MDR) <i>M. tuberculosis</i> strains. A particularly potent compound derived from 2-bromo-4-nitrosalicylaldehyde exhibited an MIC of 0.78 μM against H37Rv and demonstrated low MIC values of 6.25, 1.56, and 1.56 μM against the <i>inhA</i> + , <i>katG</i> + , and MDR strains, respectively. Molecular docking studies were also conducted to investigate the interaction of active compounds with the target enzyme InhA. Overall, the results indicate that salicylidenehydrazine derivatives represent promising lead structures for the development of new anti-TB agents effective against both drug-sensitive and drug-resistant <i>M. tuberculosis</i> strains.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing a Gold Mine of Bioactive Compounds From Natural Sources Using In Vitro, In Silico, and Network Pharmacology: A Case Study on Cachrys cristata","authors":"Inci Kurt-Celep,&nbsp;Shakeel Ahmed,&nbsp;Mehmet Veysi Cetiz,&nbsp;Abdullahi Ibrahim Uba,&nbsp;Gunes Ak,&nbsp;Selami Selvi,&nbsp;Ahmet Emir,&nbsp;Stefano Dall'Acqua,&nbsp;Gokhan Zengin","doi":"10.1002/ardp.70057","DOIUrl":"https://doi.org/10.1002/ardp.70057","url":null,"abstract":"<div>\u0000 \u0000 <p>The study aimed to explore the chemical composition and assess the wide-ranging biological effects of <i>Cachrys cristata</i> extracts, including ethyl acetate, ethanol, ethanol/water (70%), and water. We evaluated the bioactive potential of these extracts by different chemical techniques such as radical scavenging, reducing power, and metal chelation assays. Additionally, we conducted enzyme inhibition assays to target cholinesterase, tyrosinase, amylase, glucosidase, elastase, collagenase, and hyaluronidase. In the profile analysis, we determined that the main components are phenolic acids, mainly caffeic acid with the highest concentrations. The water extract of the plant showed the highest concentration of phytochemicals and superior antioxidant activity. In addition, the ethanol and ethyl acetate extracts showed the greatest level of inhibition of most of the evaluated enzymes. On the other hand, its potential protective effects against UV-induced oxidative stress, genotoxicity, and extracellular matrix (ECM) degradation were investigated. Different extracts of the plant were evaluated in terms of their effects on DNA damage, cellular viability, ECM enzymes, and matrix metalloproteinases (MMPs). COMET analysis showed that DNA breaks and genotoxicity caused by UV rays were significantly suppressed, especially by the water extract. Furthermore, network pharmacology analyses, in conjunction with in silico molecular docking and molecular dynamics simulations, demonstrated robust ligand–protein interactions and furnished insights into the underlying mechanisms, thereby substantiating the plant's therapeutic potential. Overall, our research highlights the significant potential of <i>C. cristata</i> as a valuable reservoir of bioactive chemicals that can be utilized in the health and wellness industries.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, and Biological Evaluation of Triazole Tethered Coumarin-Indole Fused Chalcone-Isatin Derivatives as a New Class of Anti-Breast Cancer Agents","authors":"Jasreen Kaur Uppal,&nbsp;Rajiv Sharma","doi":"10.1002/ardp.70060","DOIUrl":"https://doi.org/10.1002/ardp.70060","url":null,"abstract":"<div>\u0000 \u0000 <p>Inspired by the anti-breast cancer and anti-tubulin potential of coumarin, indole, chalcone, and isatin moieties, a new series of triazole-tethered coumarin-fused chalcone and isatin hybrids were designed, synthesized, and evaluated for their anti-breast cancer activities. Among the series of hybrid compounds, JKUB2 showed the strongest activity against MCF-7 breast cancer cells with an IC₅₀ value of 1.28 µM. JKUB2 exhibited tubulin polymerization inhibition potential (IC₅₀ = 1.31 µM) and induced apoptosis in breast cancer cells by arresting the cell cycle at the G2/M phase. Apart from that, JKUB2 showed higher selectivity (selectivity index: 6.36) toward MCF-7 cells over normal skin fibroblast cells (L929). Morphological studies further confirmed the capability of JKUB2 to induce cell death via apoptotic pathways. Molecular docking and dynamics simulations studies confirmed the desired interactions of JKUB2 in the colchicine binding site of microtubules, responsible for their polymerization inhibition. Overall, the study represents JKUB2 as a potential anti-breast cancer agent that acts via tubulin polymerization inhibition and induces cell death by apoptotic pathways, and warrants further research as well as acts as an effective hit lead for further development of potent and safer anti-breast cancer agents.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substituted D-Galactose-Conjugated Thiazole-Thioureas Derivatives as Promising Antidiabetic Agents: Synthesis, In Vitro Inhibition, and Molecular Simulation for α-Amylase, α-Glucosidase, Protein Glycation, and Oxidative Stress","authors":"Nguyen Dinh Thanh,&nbsp;Vu Ngoc Toan,&nbsp;Duong Ngoc Toan,&nbsp;Vu Minh Trang","doi":"10.1002/ardp.70039","DOIUrl":"https://doi.org/10.1002/ardp.70039","url":null,"abstract":"<div>\u0000 \u0000 <p>A thiourea series (<b>7a–l</b>) containing 4-arylthiazoles and the <span>d</span>-galactose moiety were synthesized and explored for their multi-target inhibition against α<i>-</i>amylase from porcine pancreas and α<i>-</i>glucosidase from <i>Saccharomyces cerevisiae</i>. Among these thioureas, <b>7h</b> was the most potent inhibitor for α-amylase (IC₅₀ of 7.84 ± 0.14 μM) and <b>7c</b> was the most potent inhibitor for α-glucosidase (IC₅₀ of 7.15 ± 0.12 μM). These thioureas also exhibited anti-glycation and antioxidant activity. They were noncytotoxic for NIH-3T3 cells. Induced-fit molecular docking study was applied to the two most potential inhibitors <b>7c</b> and <b>7h</b>. Their active interactions with residues in the catalytic pockets of the corresponding studied enzymes, 1OSE and 3TOP, were suitable to their inhibitory potentials against each tested enzyme. The molecular dynamics simulations validated the in vitro data for these compounds whereas the pharmacokinetics profile (ADMET) revealed the druglike properties of potent inhibitors.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoxazole-Based Compounds Targeting the Taxane-Binding Site of Tubulin","authors":"Miroslav Peřina,&nbsp;Márton A. Kiss,&nbsp;Jakub Bělíček,&nbsp;Veronika Vojáčková,&nbsp;Denisa Veselá,&nbsp;Renáta Minorics,&nbsp;István Zupko,&nbsp;Éva Frank,&nbsp;Radek Jorda","doi":"10.1002/ardp.70031","DOIUrl":"https://doi.org/10.1002/ardp.70031","url":null,"abstract":"<p>Taxanes and other tubulin-targeting medications are essential for treating advanced malignancies, especially in patients undergoing less aggressive chemotherapy. However, their clinical efficacy is often limited by significant off-target toxicity and adverse side effects. In this study, the synthesis and characterisation of novel steroidal A-ring-fused isoxazoles, which were obtained through iodine-mediated oxidative cyclization of dihydrotestosterone (DHT)-derived α,β-unsaturated oximes, are reported. According to mechanistic studies, the most potent compounds induced mitotic arrest and disrupted cytoskeletal integrity at low micromolar concentrations. The lead compound, <b>2j</b>, notably increased the rate of tubulin polymerisation in vitro and stabilised polymerised tubulin in the cells, leading to a G2/M block of the cell cycle. Molecular docking studies indicated that <b>2j</b> is bound preferably to the taxane site on tubulin, forming conserved interactions. MicroScale Thermophoresis was used to further study this binding and showed a nanomolar <i>K</i>_D for <b>2j</b>. The fact that <b>2j</b> maintained its activity in docetaxel-resistant prostate cancer cells, demonstrating its ability to circumvent resistance pathways linked to existing therapies with taxane-like drugs, supports its clinical relevance. Therefore, our results encourage additional research and development for its potential therapeutic use in cancer treatment, particularly in resistant cases.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient Acyloxymethylation of Psilocin and Other Tryptamines Yielding ACOM Prodrugs for Psychedelic-Assisted Therapy","authors":"Judith Stirn,&nbsp;Christian D. Klein","doi":"10.1002/ardp.70022","DOIUrl":"https://doi.org/10.1002/ardp.70022","url":null,"abstract":"<p>Acyloxymethyl (ACOM) derivatives of tryptamines such as the psychedelic drug psilocin and the anti-migraine drug sumatriptan bear potential as prodrugs. Previous synthetic approaches suffer from insufficient chemoselectivity between the desired functionalization of the phenolic (psilocin) or sulfonamide (sumatriptan) groups versus other reactive groups in the parent drugs. We report a novel synthetic route toward ACOM prodrugs of tryptamines via the chemoselective installation of a carbamate protecting group at the indole nitrogen by means of a Heller–Sarpong reagent and final deprotection under extremely mild conditions. This enables delicate transformations such as the <i>O</i>-acyloxymethylation of psilocin or the <i>N</i>^<i>2</i>-acyloxymethylation of sumatriptan. Several novel <i>O</i>-ACOM ethers of hydroxytryptamines were obtained and evaluated in vitro for their potential as novel prodrugs for psychedelic therapy. The rate of bioactivation in human plasma may be adjusted to rapid (<i>t</i>_1/2 &lt; 1 min) or slow (<i>t</i>_1/2 &gt; 240 min) kinetics by varying the acyl residue in the ACOM promoiety. Irrespective of the acyl residue, short half-lives in human saliva will likely preclude the sublingual or buccal application of ACOM ether prodrugs of hydroxytryptamines, while other routes such as peroral, transdermal, nasal, or intravenous administration may be pursued.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green Synthetic Strategies for Pyrazole Derivatives: A Comprehensive Review","authors":"Radhika Kachhadiya,&nbsp;Drashti Shah,&nbsp;Apurva Prajapati,&nbsp;Ashish Patel","doi":"10.1002/ardp.70055","DOIUrl":"https://doi.org/10.1002/ardp.70055","url":null,"abstract":"<div>\u0000 \u0000 <p>Pyrazole derivatives have emerged as a vital class of heterocyclic compounds due to their wide range of biological activities and promising therapeutic applications. In recent years, the shift toward greener and more sustainable chemical practices has fueled interest in the eco-friendly synthesis of pyrazole-based molecules. This review presents recent advancements in the green synthesis of pyrazole scaffolds, with a special focus on methods that avoid hazardous reagents, employ green solvents, utilize renewable energy sources, and incorporate recyclable catalysts. Emphasis is placed on synthetic strategies that are not only efficient and high-yielding but also operationally simple, atom-economical, and environmentally benign. Mechanistic insights into selected reactions are also provided to illustrate functional group tolerance and reaction efficiency. Overall, this review captures the growing role of green chemistry in heterocyclic synthesis and highlights its significance in developing sustainable pathways for pyrazole derivatives, serving as a valuable reference for researchers in both academia and industry.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Molecular Mechanisms Underlying the Antineoplastic Profile of Vitexin 2″-O-α-L-Rhamnopyranoside From Cordyline australis (G.Frost.): Isolation and Constituent Profiling","authors":"Mona A. Raslan,&nbsp;Marwa M. Mounier,&nbsp;Rehab F. Taher","doi":"10.1002/ardp.70054","DOIUrl":"https://doi.org/10.1002/ardp.70054","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Cordyline australis</i> (G.Forst.) Endl. Red Star leaves have been used in traditional medicine for several disorders. This study investigated the anticancer potential of <i>C. australis</i> leaves extract and characterized its bioactive constituents. Three compounds, a steroidal saponin, fruticoside K <b>23</b>, and two flavonoids, vitexin 2″-<i>O</i>-<i>α</i>-<span>l</span>-rhamnopyranoside <b>35</b> and helichrysoside <b>68</b>, were isolated and identified from its aqueous methanolic extract (CAME) using column chromatography. Seventy-nine additional compounds were tentatively identified using high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) analysis and The Global Natural Product Social Molecular Networking (GNPS-MN), with 57 compounds reported for the first time in the <i>Cordyline</i> genus. CAME and its isolated compounds were evaluated for cytotoxicity by MTT assay against seven different cancer cell lines. Vitexin 2″-<i>O</i>-<i>α</i>-<span>l</span>-rhamnopyranoside <b>35</b> exhibited significant cytotoxicity against HCT-116 colon cancer cells. Additionally, CAME, fruticoside K <b>23</b>, and vitexin 2″-<i>O</i>-<i>α</i>-<span>l</span>-rhamnopyranoside <b>35</b> demonstrated significant cytotoxicity against osteosarcoma (HOS) cells. Afterwards, the safety profile of CAME and all the isolated compounds were examined upon human normal cells BJ-1. At 100 μg/mL, CAME and all isolated compounds showed a safe response on human normal BJ-1 cells (0.6%–8.5% cytotoxicity). Vitexin 2″-<i>O</i>-<i>α</i>-<span>l</span>-rhamnopyranoside <b>35</b> possessed the most significant selective anticancer response on osteosarcoma cells (HOS), with the least IC₅₀ value of 43.7 μg/mL. It induced apoptosis in HOS cells by modulating Bax, Bcl-2, and caspase-3 expression and caused G1 phase cell-cycle arrest. These results highlight <i>C. australis</i> as a source of potential anticancer agents, particularly vitexin 2″-<i>O</i>-<i>α</i>-<span>l</span>-rhamnopyranoside <b>35</b>, which warrants further investigation for its therapeutic potential.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, In Vitro, and In Silico Studies of 5-(Diethylamino)-2-Formylphenyl Naphthalene-2-Sulfonate Based Thiosemicarbazones as Potent Anti-Alzheimer Agents","authors":"Urva Farooq,&nbsp;Muhammad Islam,&nbsp;Zahra Batool,&nbsp;Suraj N. Mali,&nbsp;Rahul D. Jawarkar,&nbsp;Shailesh S. Gurav,&nbsp;Rima D. Alharthy,&nbsp;Halil Şenol,&nbsp;Nastaran Sadeghian,&nbsp;Parham Taslimi,&nbsp;Zahid Shafiq,&nbsp;Silvia Schenone","doi":"10.1002/ardp.70050","DOIUrl":"https://doi.org/10.1002/ardp.70050","url":null,"abstract":"<p>Alzheimer's disease (AD) is known as one of the more devastating neurodegenerative diseases diagnosed in older people. Cholinesterase inhibitors (ChEI) can be used as an effective palliative treatment for AD. An extensive range of new biologically active 4-(diethylamino) salicylaldehyde-based thiosemicarbazone derivatives <b>5(a–u)</b> was synthesized and evaluated as inhibitors of cholinesterase (ChE) and monoamine oxidase (MAO) enzymes. 2,3-Dichloro-substituted compound <b>5u</b> was the most potent inhibitor of AChE and MAO-A with IC₅₀ values of 12.89 and 96.25 nM, respectively. In contrast, the 2,3-dichlorophenyl-substituted compound <b>5a</b> was the most powerful inhibitor of BChE, with an IC₅₀ value of 124.72 nM. Structure–activity analysis revealed that the electron-withdrawing substituents on the phenyl ring play a crucial role in the inhibition potential of synthesized compounds. Compound <b>5a</b> showed the strongest binding with 4BDS (−11.3 kcal/mol) via hydrogen bonds and π-interactions. Compound <b>5u</b> exhibited high affinity with 1B41 (−8.2 kcal/mol), 2Z5X (−8.6 kcal/mol), and 2V5Z (−7.8 kcal/mol), forming key hydrogen bonds, salt bridges, and π-interactions, highlighting its multi-target potential. In silico ADME, pharmacokinetics, and drug-likeness studies were conducted and compared with the standard drugs galantamine and clorgyline.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}