Archiv der Pharmazie最新文献

{"title":"Development of 1,2,3-Triazoles as Dual Enzyme Inhibitors Targeting α-Amylase and α-Glucosidase for Type 2 Diabetes Intervention","authors":"K. Sruthi,&nbsp;S. L. Manju","doi":"10.1002/ardp.70088","DOIUrl":"https://doi.org/10.1002/ardp.70088","url":null,"abstract":"<div>\u0000 \u0000 <p>A series of fifteen 1,2,3-triazole derivatives <b>6(a–o)</b> were developed and evaluated for their inhibitory effects on carbohydrate-hydrolyzing enzymes implicated in Type 2 diabetes management. The compounds were assessed through in silico studies (including molecular docking and ADME predictions) and in vitro assays such as α-amylase, α-glucosidase, and antioxidant activities. Notably, the compounds <b>6a</b>, <b>6d</b>, <b>6g</b>, <b>6h</b>, <b>6k</b>, <b>6l</b>, and <b>6n</b> exhibited dual inhibition against both enzymes. Among them, compound <b>6a</b> exhibited the most potent α-glucosidase inhibition (IC₅₀ = 22.15 ± 0.75 µM), comparable to the reference drug acarbose (IC₅₀ = 21.07 ± 0.05 µM). Meanwhile, compound <b>6h</b> demonstrated strong α-amylase inhibition (IC₅₀ = 84.46 ± 1.14 µM) compared with standard acarbose (IC₅₀ = 87.62 ± 0.47 µM). Cytotoxicity studies of the most active compounds <b>6a</b> and <b>6h</b> indicated moderate cytotoxicity, with IC₅₀ values of 32.87 ± 1.2 µM and 32.42 ± 1.5 µM, respectively, suggesting a reasonable safety margin compatible with continued drug development. The DPPH assay revealed moderate to good activity for all compounds <b>6(a–o)</b>, with IC₅₀ values ranging from 39.60 ± 0.15 to 99.45 ± 0.12 µM. These findings support the therapeutic potential of these compounds as antidiabetic agents.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929635","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":"Synthesis, Identification, and Characterization of a Novel 1,2,5-Selenadiazole Derivative as a Microtubule Targeting Agent That Overcomes Multidrug Resistance","authors":"Farhat Firdous,&nbsp;Syed Usama Bin Farrukh,&nbsp;Muhammad Furqan,&nbsp;Sana Shaukat,&nbsp;Salman Fozail,&nbsp;Sebastian Öther-Gee Pohl,&nbsp;Aslıhan Bastem Akan,&nbsp;Kevin B. Myant,&nbsp;Fatimah Alahmari,&nbsp;Abdul-Hamid Emwas,&nbsp;Mariusz Jaremko,&nbsp;Ghayoor Abbas,&nbsp;Rahman Shah Zaib Saleem,&nbsp;Amir Faisal","doi":"10.1002/ardp.70087","DOIUrl":"https://doi.org/10.1002/ardp.70087","url":null,"abstract":"<div>\u0000 \u0000 <p>Microtubules are crucial for various cellular processes, including cell division, where they form highly dynamic spindle fibers for chromosomal alignment and segregation. Interference with microtubule dynamics through microtubule targeting agents (MTAs) blocks progression through mitosis, ultimately resulting in apoptosis. Although MTAs have been effectively used as a frontline treatment for various cancers, multidrug resistance (MDR) often limits their effectiveness. This study focuses on selenadiazoles, a group of organic selenium compounds with anticancer activities. Eighteen novel 1,2,5-selenadiazole derivatives were synthesized, three of which (<b>9d</b>, <b>9f</b>, and <b>9i</b>) showed potent antiproliferative activity in HCT116 colorectal cancer cells. Treatment of cells with <b>9f</b> (SSE1706), one of the most potent compounds (GI₅₀ value of 1.89 ± 0.99 µM), disrupted mitotic spindle formation, leading to G2/M arrest. <b>9f</b> inhibited microtubule polymerization in cell-based assays, and long-term treatment with <b>9f</b> stabilized p53 and induced apoptosis. Moreover, <b>9f</b> effectively inhibited the growth of mouse and human colon cancer-derived organoids. Finally, <b>9f</b> exhibited potent antiproliferative activity against MDR-1 overexpressing KB-V1 cells, highlighting its potential to overcome MDR. These findings suggest <b>9f</b> as a lead compound for further optimization studies, particularly targeting MDR.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929956","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":"Isotretinoin as a Multifunctional Anticancer Agent: Molecular Mechanisms, Pharmacological Insights and Therapeutic Potential","authors":"Pritam Sarkar,&nbsp;Nasrin Sultana,&nbsp;Prottoy Kumar Debnath,&nbsp;Razina Rouf,&nbsp;Mohammad S. Mubarak,&nbsp;Shaikh Jamal Uddin,&nbsp;Dragoş Popa,&nbsp;Daniela Calina,&nbsp;Javad Sharifi-Rad","doi":"10.1002/ardp.70084","DOIUrl":"https://doi.org/10.1002/ardp.70084","url":null,"abstract":"<div>\u0000 \u0000 <p>Despite notable advancements in conventional cancer therapies, challenges such as drug resistance, adverse effects, and high treatment costs remain significant obstacles. This situation calls for exploring new therapeutic options. One promising approach is drug repurposing, which uses existing medications with known effects to identify new anticancer agents. Isotretinoin (13-<i>cis</i>-retinoic acid), a vitamin A derivative typically used to treat severe acne, shows considerable potential as an anticancer agent. Recent studies suggest that isotretinoin has the potential to enhance the efficacy of cancer treatment and contribute to cancer inhibition by targeting specific molecular pathways. This review explores isotretinoin's chemistry, pharmacokinetics, and toxicity, emphasizing its role in cancer treatment through clinical and preclinical studies while elucidating its anticancer mechanisms. Both preclinical and clinical studies have revealed that isotretinoin can effectively inhibit the growth of tumor cells, induce apoptosis, and help regulate cellular differentiation in a range of cancers, including neuroblastoma, glioblastoma, breast, skin, lung, ovarian, cervical, and head and neck cancers. Isotretinoin works against cancer through several mechanisms. It activates retinoic acid receptors (RARs), suppresses oncogenic signaling pathways, and influences gene transcription related to cell cycle control and apoptosis. Moreover, combining isotretinoin with other treatments, like interferon-alpha, chemotherapy drugs, or other targeted inhibitors, can create synergistic effects that improve treatment effectiveness and potentially lessen side effects. Although isotretinoin holds great promise, we still need more research to address its limitations, such as its toxicity, risks during pregnancy, and differing responses in various cancer types. Current research focuses on optimizing isotretinoin-based therapies by refining dosage regimens to maximize efficacy and enhancing formulation strategies for improved absorption and reduced side effects. Ultimately, the use of isotretinoin in cancer treatment demonstrates the potential of repurposing established drugs and paves the way for more accessible and cost-effective cancer therapies.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929957","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":"Synthesis, Characterization, and Comprehensive In Vitro and In Silico Evaluation of the Anti-Inflammatory Potential of Novel 1,2,3-Triazole–Arylidenehydrazide/Thiazolidinone Hybrids","authors":"Nihan Aktaş Pepe,&nbsp;Furkan Çakır,&nbsp;Tuğba Atalay,&nbsp;Büşra Acar,&nbsp;Gurbet Çelik Turgut,&nbsp;Alaattin Şen,&nbsp;Halil Şenol","doi":"10.1002/ardp.70081","DOIUrl":"https://doi.org/10.1002/ardp.70081","url":null,"abstract":"<div>\u0000 \u0000 <p>Five novel 1,2,3-triazole/arylidenehydrazide/thiazolidinone hybrid compounds (<b>7–11</b>) were synthesized and characterized using NMR, HRMS, IR, and HPLC purity analysis. The cytotoxicity of these compounds was evaluated on fibroblasts and THP-1 cells, showing that all compounds were nontoxic at the tested concentrations. The wound healing assay revealed that compounds <b>7</b>, <b>9</b>, and <b>10</b> significantly enhanced wound closure, with a 7.74%–32.69% improvement in treated cells. Compounds <b>8</b> and <b>11</b> showed moderate effects. Anti-inflammatory activity was assessed through qRT-PCR, demonstrating that compound <b>10</b> led to the most significant reduction in proinflammatory cytokines TNF-α, IL-1β, and NF-κB1. In addition, the expression of Iba1 protein in THP-1 cells confirmed that compound <b>8</b> showed the strongest anti-inflammatory effect, surpassing that of aspirin. Compound <b>10</b> showed the highest inhibition of NF-κB signaling and iNOS activity. Molecular docking studies revealed that compounds <b>10</b> and <b>11</b> had strong binding affinities to TNF-α and iNOS, with compound <b>11</b> showing the most stable interactions. Molecular dynamics simulations supported these findings, indicating that compound <b>11</b> demonstrated more stable binding to both targets. Overall, the results suggest that compounds <b>10</b> and <b>11</b> are promising anti-inflammatory candidates with potential for further development in therapeutic applications for inflammatory diseases.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929979","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":"Targeting JNK1/2 and P38 Mitogen-Activated Protein Kinases With Pazopanib Mitigates Bleomycin-Induced Lung Fibrosis.","authors":"Rasha Abdelhady, Rabab H Sayed, Nancy S Younis, Omaima Ali, Mai Abdallah Elhemely, Ahmed M Ashour, Shuruq E Alsufyani, Hany H Arab, Mohammed S Abdel-Hamid","doi":"10.1002/ardp.70105","DOIUrl":"10.1002/ardp.70105","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis is considered the most common type of interstitial lung disease. The principal aim of our research was to investigate the potential role of pazopanib treatment in alleviating bleomycin-elicited pulmonary fibrosis and elucidate the underlying molecular mechanisms. Twenty-four male mice were allocated into four groups (n = 6): control animals (received saline intraperitoneally (i.p.)), bleomycin group received bleomycin (40 U/kg, i.p.) on 5 days, 0, 3, 7, 10, and 14, and bleomycin and pazopanib-treated group received bleomycin on the specified days and then received pazopanib (10 mg/kg, i.p.) once daily starting on Day 15 to Day 28, plus pazopanib-treated group, which received pazopanib only in the previously specified dose and duration. Our results demonstrated the promising role of pazopanib in mitigating pulmonary fibrosis, as reflected by the remarkable improvement in body weight loss and pulmonary histopathological features. This finding was primarily ascribed to the documented suppression of mitogen-activated protein kinase kinase kinase 2 (MEKK2) and MEKK3 mRNA expressions, which subsequently repressed p-c-Jun N-terminal kinase (p-JNK1/2) and p-P38 group of protein kinases (p-P38) protein expressions. Moreover, pazopanib administration to bleomycin-treated mice remarkably adjusted the bleomycin-mediated dysregulation of the levels of examined cytokines, including interleukin (IL)-1β, IL-13, IL-33, tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-B (NF-κB) P65. Remarkably, pazopanib treatment reversed the bleomycin-induced elevation in transforming growth factor-beta-1 (TGF-β1) and α-smooth muscle actin (α-SMA) levels. Our research highlighted the beneficial role of pazopanib in attenuating bleomycin-elicited lung fibrosis through the suppression of MEKK2 and MEKK3 and the modulation of JNK and P38 cascades.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":"e70105"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184239","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":"The Potential of Resveratrol as an Anticancer Agent: Updated Overview of Mechanisms, Applications, and Perspectives.","authors":"Md Rezaul Islam, Rahaf Ajaj, Abdur Rauf, Sanzida Sharmin Shanta, Md Ibrahim Khalil Al-Imran, Md Naeem Hossain Fakir, Alessandra Gianoncelli, Giovanni Ribaudo","doi":"10.1002/ardp.70109","DOIUrl":"https://doi.org/10.1002/ardp.70109","url":null,"abstract":"<p><p>The natural polyphenol resveratrol, found in several plants, has garnered significant interest due to its beneficial effects on health and for its potential anticancer properties. Studies have demonstrated that it can alter various signaling pathways linked to cancer development and that it inhibits tumor development and spread by exerting several antiproliferative, proapoptotic, anti-inflammatory, and antiangiogenic mechanisms. Its role in regulating oxidative stress and epigenetic modifications further enhances its therapeutic potential. Nevertheless, despite promising preclinical results, clinical translation is to some extent limited by bioavailability, metabolism, and dosage. This updated review explores the mechanisms, also from a structural point of view, behind the anticancer properties of resveratrol, focusing on its impact on crucial signaling networks in different cancer models. Additionally, it overviews the current limitations of resveratrol-based treatments and suggests potential improvements through innovative delivery methods, drug combination approaches, and development of new derivatives. This review was conceived as an update with respect to contributions already present in the literature, thus particular attention has been dedicated to the contribution reported in the literature within the last 5 years and to these studies reporting in vivo data.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":"e70109"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184273","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 Role of the AMY1 Receptor Signaling Cascade in the Protective Effect of Sulforaphane Against Nitroglycerin-Induced Migraine in Mice.","authors":"Luejine A Elbendary, Ghada A Abdel-Latif, Mohamed A Khattab, Ayman E El-Sahar, Rabab H Sayed","doi":"10.1002/ardp.70107","DOIUrl":"https://doi.org/10.1002/ardp.70107","url":null,"abstract":"<p><p>Migraine is a prevalent neurological disorder that is more commonly observed in women than in men. The activation of trigeminal vascular pathways and the release of calcitonin gene-related peptide (CGRP) are central to its pathogenesis. Notably, amylin and CGRP share the amylin-1 (AMY1) receptor, which is expressed in key structures implicated in migraine mechanisms. Recent research has highlighted the AMY1 receptor as a promising therapeutic target for migraine treatment. Sulforaphane, a natural compound recognized for its neuroprotective and anti-inflammatory effects, has gained interest for its potential benefits in this context. This study evaluated the protective effects of sulforaphane against nitroglycerin induced migraine in female mice, comparing its efficacy to the standard migraine medication, topiramate. Migraine was induced using nitroglycerin (10 mg/kg, i.p., administered every other day), and treatments included sulforaphane (5 mg/kg/day, i.p.) or topiramate (30 mg/kg/day, i.p.) for a duration of 9 days. Sulforaphane demonstrated significant improvements in behavioral symptoms such as photophobia, head grooming, and both mechanical and thermal allodynia. These behavioral changes were accompanied by reductions in serum levels of nitric oxide, CGRP, and pro-inflammatory cytokines. Histological analysis revealed that sulforaphane ameliorated nitroglycerin induced damage in the trigeminal ganglia and trigeminal nucleus caudalis. Additionally, sulforaphane reduced AMY1 receptor expression in the medulla and inhibited its downstream signaling components, including phosphorylated ERK1/2, P38, and c-Fos. Sulforaphane further enhanced the Nrf2/HO-1 pathway while suppressing the NF-κB/NLRP3/caspase-1 signaling cascade. The findings suggest that sulforaphane may offer a novel therapeutic approach for managing migraines by modulating AMY1 receptor-related signaling pathways.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":"e70107"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184263","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":"New 1,3,4-Thiadiazole-Based Dual B-Raf/VEGFR-2 Inhibitors With Potential Anti-Breast Activity: Design, Synthesis, In Vitro and In Silico Evaluations.","authors":"Walid E Elgammal, Hazem Elkady, Hazem A Mahdy, Bshra A Alsfouk, Dalal Z Husein, Fatma G Amin, Abdelrahman A Abuelkhir, Eslam B Elkaeed, Ahmed M Metwaly, Ibrahim H Eissa","doi":"10.1002/ardp.70097","DOIUrl":"https://doi.org/10.1002/ardp.70097","url":null,"abstract":"<p><p>This study reports the design, synthesis, and biological evaluation of a novel series of 1,3,4-thiadiazole-based derivatives as dual B-Raf and VEGFR-2 kinase inhibitors with potential anticancer activity. Among the synthesized compounds, 7b emerged as the most potent candidate, exhibiting strong cytotoxicity against the MDA-MB-231 and MCF-7 breast cancer cell lines (IC₅₀ = 9.66 and 15.83 µM, respectively), with minimal toxicity toward normal WI-38 and WISH cells, reflected by favorable selectivity indices. Compound 7b, featuring a unique structural assembly of a 2,3-dihydro-1,3,4-thiadiazole core, a para-methoxyphenyl group, and a sulfonamide-linked methylpiperidine moiety, exhibited superior dual-inhibitory activity. It showed IC₅₀ values of 0.75 µM for B-Raf and 58.13 nM for VEGFR-2. Flow cytometry and gene expression analysis revealed that 7b induces G1-phase cell-cycle arrest and promotes apoptosis through the upregulation of BAX, caspases-8/9, and downregulation of Bcl-2. Compound 7b also inhibited cell migration in wound-healing assays. Structure-activity relationship (SAR) analysis indicated that para-substituted electron-donating groups enhanced cytotoxic potency. Molecular docking and molecular dynamics simulations confirmed the stable binding of 7b to the kinase active sites, supported by favorable Glide scores (-25.47 kcal/mol for VEGFR-2 and -31.64 kcal/mol) and MM-GBSA (molecular mechanics with generalized Born and surface area solvation) binding energies. Density functional theory (DFT) calculations further validated the compound's electronic stability and reactivity. These integrated findings suggest that compound 7b is a promising lead for further development as a selective dual kinase inhibitor for breast cancer therapy.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":"e70097"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184224","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":"Synthesis, Biological Evaluation and Molecular Docking Studies of Novel 4-Propylsulfonylpiperazines-Based Thiosemicarbazones as Ecto-5'-Nucleotidase and NTPDase Inhibitors.","authors":"Hina Aftab, Shireen Mona Dutt, Suraj N Mali, Erica Vigiani, Julie Pelletier, Jean Sévigny, Shailesh S Gurav, Rahul D Jawarkar, Abdulraheem Sa Almalki, Muhammad Safwan Akram, Zahra Batool, Silvia Schenone, Jamshed Iqbal, Zahid Shafiq","doi":"10.1002/ardp.70098","DOIUrl":"https://doi.org/10.1002/ardp.70098","url":null,"abstract":"<p><p>Purinergic signaling is modulated by extracellular enzymes known as ectonucleotidases. Ecto-5'-nucleotidase and NTPDases are part of the ectonucleotidase family. NTPDases control ATP levels through hydrolysis, whereas ecto-5'-NT collaborates with NTPDase to break down nucleotide molecule. Due to their roles in inflammation, infection, and cancer, both enzymes present promising targets for therapeutic interventions. In this study, we present a novel and environment-friendly synthetic approach for the creation of small molecules that are not based on nucleotides, specifically substituted sulfonyl-piperazine-based thiosemicarbazone derivatives 7(a-s). We assessed their inhibitory effects on ecto-5'-nucleotidase and NTPDase1, 2, 3, and 8. Most of the compounds displayed excellent inhibition against one or more forms, while some displayed selective inhibition. To gain a deeper understanding of how the synthesized compounds interact with the isoenzymes, we conducted molecular docking studies. Additionally, ADME analyses were performed to predict the pharmacokinetic properties of these compounds. The integration of in vitro and in silico studies enabled the identification of compounds with potential inhibitory activity and favorable binding orientations. The observed results provide compelling evidence for the potency of the biologically active scaffold, sulfonylpiperazine, as a powerful and selective NTPDase inhibitor.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":"e70098"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184295","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":"In Vitro Modeling of the Antitumor Drugs Effects on the Endothelial Barrier Function.","authors":"Aleksandra S Churkina, Kseniya N Sedenkova, Polina А Kovaleva, Anton S Shakhov, Anatoly A Kotlobay, Elena B Averina, Irina B Alieva","doi":"10.1002/ardp.70104","DOIUrl":"https://doi.org/10.1002/ardp.70104","url":null,"abstract":"<p><p>Pulmonary edema and acute respiratory failure, developing due to the vascular endothelium dysfunction, are common side effects of anticancer therapy. This study is the first approach to create an in vitro model system to estimate vascular response at the drug development/improvement stage and to determine whether it is possible to select an antitumor drug dose effectively suppressing malignant cells without a pathological effect on the endothelial cells function. In this study (1) the doses of several clinically used antitumor drugs suppressing the common tumor cell proliferation were determined experimentally; (2) the endothelial cell viability after exposure to selected doses of these drugs was assessed in vitro; (3) changes in the endothelial monolayer condition, as well as cultured endothelial cell reactions and intracellular disorders accompanying the effects of selected drugs doses were studied in vitro using the intravital observations and super-resolution microscopy methods. This approach allowed to select antitumor drug concentrations inhibiting cell proliferation in selected tumor lines, but having no critical effect on the viability of endothelial cells and their cytoskeletal structures. As the result, an in vitro model system for studying the side effects of medications on vascular permeability was created.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":"e70104"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184306","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}