Archiv der Pharmazie最新文献

{"title":"Exploration of Fluorinated Peptoid-Based Histone Deacetylase Inhibitors as Dual-Stage Antiplasmodial Agents","authors":"Nina Reßing,&nbsp;Daniel Stopper,&nbsp;Thomas Martin Schäfer,&nbsp;Lais Pessanha de Carvalho,&nbsp;Elizabeth A. Winzeler,&nbsp;Jana Held,&nbsp;Finn K. Hansen","doi":"10.1002/ardp.70071","DOIUrl":"https://doi.org/10.1002/ardp.70071","url":null,"abstract":"<p>The antiplasmodial properties of a series of fluorinated peptoid-capped histone deacetylase inhibitors (HDACi) were investigated against asexual blood stages of the drug-sensitive 3D7 and drug-resistant Dd2 strains of <i>Plasmodium falciparum</i>, as well as the exo-erythrocytic liver stages and mature gametocytes. Among the series, compound <b>1h</b> emerged as the most potent derivative, showing strong activity against both <i>P. falciparum</i> strains (<i>Pf</i> 3D7 and Dd2 IC₅₀: 0.010 μM) and <i>Plasmodium berghei</i> liver stages (<i>Pb</i> EEF IC₅₀: 0.74 μM), while lacking activity against mature gametocytes. Compound <b>1b</b> was identified as a second hit compound with slightly lower activity against asexual blood and liver stages (<i>Pf</i> 3D7 IC₅₀: 0.019 μM; <i>Pf</i> Dd2 IC₅₀: 0.023 μM; <i>Pb</i> EEF IC₅₀: 2.25 μM) but showed excellent parasite selectivity (SI^HepG2/3D7: 2389; SI^HepG2/Dd2: 1973) and low single-digit micromolar activity against mature gametocytes (IC₅₀: 1.70 μM). Compared to our previous hit compound MAHA-022, both <b>1b</b> and <b>1h</b> exhibited improved activity against asexual blood stages and enhanced parasite selectivity, albeit with reduced activity against liver stage parasites. Taken together, compounds <b>1b</b> and <b>1h</b> represent promising multi-stage antiplasmodial HDACi scaffolds for further development and optimization.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810943","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":"Hydroxamic Acid Hybrids for Lung Cancer Therapy","authors":"Donghong Wang,&nbsp;Yanjing Cheng,&nbsp;Aimei Liu,&nbsp;Yafei Zhuang","doi":"10.1002/ardp.70067","DOIUrl":"https://doi.org/10.1002/ardp.70067","url":null,"abstract":"<div>\u0000 \u0000 <p>Lung cancer is one of the most common and deadly cancers across the world nowadays, and the morbidity and mortality of lung cancer will continue to increase for a long period. Chemotherapy, which can kill cancer cells, shrink tumors, and improve patient survival and quality of life, plays a crucial role in lung cancer therapy. However, chemotherapy has several disadvantages, mainly manifested in severe side effects, limited efficacy, and the tendency to develop drug resistance. Histone deacetylase (HDAC) inhibitors, which work by inhibiting the activity of HDACs, can help to re-express tumor-suppressor genes that have been silenced due to epigenetic changes, thus inhibiting the growth and proliferation of lung cancer cells. Hydroxamic acid hybrids as potent HDAC inhibitors exhibited robust in vitro and in vivo efficacy against drug-sensitive and drug-resistant lung cancers, representing crucial templates in creating innovative anti-lung cancer agents. This article will introduce the latest research progress on hydroxamic acid hybrids with anti-lung cancer activity developed since 2020. The structure–activity relationships will be summarized, and the mechanisms of action will be discussed to provide references for future research.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810942","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":"Issue Information: Arch Pharm (8/2025)","authors":"","doi":"10.1002/ardp.70051","DOIUrl":"https://doi.org/10.1002/ardp.70051","url":null,"abstract":"","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773926","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":"Rational Design of 6-Amino-2-Piperazinylpyridine-Based ROCK2 Inhibitors With Anti-Breast Cancer Metastatic Efficiency.","authors":"Haoran Chen, Shuqi Wang, Shanbao Bu, Zhi Cao, Xue Fan, Nan Jiang, Xin Zhai","doi":"10.1002/ardp.70068","DOIUrl":"https://doi.org/10.1002/ardp.70068","url":null,"abstract":"<p><p>Rho-associated coiled coil kinase (ROCK) plays a pivotal role in regulating actin cytoskeleton remodeling and cellular motility, establishing it as a promising therapeutic target for metastatic breast cancer. Guided by the lead compound belumosudil, a novel series of ROCK2 inhibitors based on a 6-amino-2-piperazine pyridine scaffold was designed and synthesized. The Kinase-Glo assay identified compound 14r as the most potent analog, showing an IC₅₀ value of 82.6 nM, which represented a 1.2-fold improvement over belumosudil. Furthermore, the morphology of MDA-MB-231 cells treated with 14r was significantly changed in immunofluorescent staining analysis. Simultaneously, cell scratch experiments showed that 14r inhibited the migration of MDA-MB-231 cells in a dose-dependent manner. Additionally, molecular docking studies elucidated the binding mode of 14r within the ROCK2 ATP pocket, corroborating its nanomolar-level inhibitory activity. In conclusion, 14r showed great potential for further optimization to suppress breast cancer metastasis.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":"e70068"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793029","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":"Antimicrobial and Antioxidant Electrospun Membrane Incorporating Silver and Copper Complexes of Phenylboronic Acid-Functionalized 4,5-Diazafluorene Ligand.","authors":"Seçil Kaya, Caner Cebeci, Hande Hançer, Buşra Akgül, Ibrahim Erden, Tülin Özbek, Emrah Şefik Abamor, Serap Acar","doi":"10.1002/ardp.70072","DOIUrl":"https://doi.org/10.1002/ardp.70072","url":null,"abstract":"<p><p>Thermally crosslinked polyacrylic acid (PAA)-polyvinyl alcohol (PVA) nanofibrous (NFC) membranes were developed via electrospinning for potential wound dressing applications with antioxidant and antimicrobial properties. Silver and copper complexes (AgSK and CuSK) of a phenylboronic acid-functionalized 4,5-diazafluorene ligand (SK) were synthesized, characterized, and incorporated into the membranes. SEM imaging revealed uniform, bead-free nanofibers with an average diameter of 725.35 ± 173.79 nm. FTIR analysis confirmed the successful incorporation of compounds through characteristic C═N stretching bands at 1620-1630 cm^-1. DPPH assay showed that SK, AgSK, and CuSK exhibited antioxidant activities of 54.6 ± 2.5%, 88.4 ± 3.5%, and 79.6 ± 3.4% at 90 min, respectively. Incorporation into the nanofibers did not significantly alter antioxidant performance. Antimicrobial activity was assessed against Escherichia coli, Staphylococcus aureus, and Candida albicans. AgSK showed the strongest inhibition, with MIC values of 62.5, 31.25, and 125 µg/mL, respectively. AgSK-loaded membranes (AgSK-NFC) demonstrate antimicrobial activity with > 98% reduction in all tested strains. Biocompatibility tests with L929 fibroblasts showed improved cell viability upon membrane incorporation. The membranes also exhibited high swelling capacity, good water resistance, and sustained release over 7 days. With this study, for the first time, the use of 4,5-diazafluorene and its metal complexes in nanofibrous membranes has been demonstrated. Thus, an interdisciplinary approach combining materials science and coordination chemistry is established, broadening the scope for future developments in nanofiber-based technologies.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":"e70072"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797714","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":"Current Landscape of Hydroxamic Acid Derivatives With Antileukemia Activity","authors":"Yao Qu,&nbsp;Chang-Jin Yuan","doi":"10.1002/ardp.70056","DOIUrl":"https://doi.org/10.1002/ardp.70056","url":null,"abstract":"<div>\u0000 \u0000 <p>Leukemia, as the second most prevalent hematological malignancy, could disrupt the production of healthy blood cells in the bone marrow, leading to anemia, neutropenia, and thrombocytopenia, and constitutes a significant global health burden. Chemotherapy remains a cornerstone of leukemia treatment, but drug resistance and severe adverse effects are the main culprits for its failure in treating leukemia, thereby creating an urgent imperative to develop innovative anti-leukemia agents. Hydroxamic acid derivatives, recognized as prominent histone deacetylase (HDAC) inhibitors, represent a promising class of agents in leukemia therapy, leveraging epigenetic modulation, multi-target activity, and synergistic potential to address unmet drug resistance and toxicity needs. This review summarizes the latest advancements in hydroxamic acid derivatives, including hydroxamic acid-azole hybrids, hydroxamic acid-indole hybrids, hydroxamic acid-pyridine/quinoline hybrids, and hydroxamic acid-(fused) pyrimidine hybrids, with therapeutic potential against leukemia, covering articles published from 2020 to the present. The structure–activity relationships and the mechanisms of action are also discussed to guide the rational design and development of more effective and less toxic therapeutic candidates.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725526","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":"Current Landscape of Hydroxamic Acid Hybrids With Anti-Colorectal Cancer Potential","authors":"Yanjing Cheng,&nbsp;Yafei Zhuang,&nbsp;Ni Zhu,&nbsp;You Yu,&nbsp;Meichun Hu","doi":"10.1002/ardp.70066","DOIUrl":"https://doi.org/10.1002/ardp.70066","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer, also referred to as colon cancer, is a malignant tumor originating from the inner lining of the rectum or colon, the longest segment of the large intestine. As one of the most prevalent digestive system cancers globally, colorectal cancer ranks third among all cancers worldwide, comprising approximately 10% of all new cancer cases, and poses a serious threat to human life and health. Hydroxamic acid hybrids as potential histone deacetylase (HDAC) inhibitors could exert anti-colorectal cancer effects through multiple interconnected pathways, primarily targeting key molecular and cellular processes involved in tumor growth, progression, and metastasis. Moreover, hydroxamic acid hybrids can simultaneously target two or more distinct cancer sites, thereby potentially enhancing therapeutic efficacy, overcoming drug resistance, improving pharmacokinetic properties, and minimizing side effects. This review outlines the current landscape of hydroxamic acid hybrids with potential anti-colorectal cancer properties, developed from 2020 to the present, aiming to open new avenues for exploring novel candidates.</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":"144716999","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":"Structure-Driven Mechanisms and Synergistic Approaches of Polyphyllin VII in Breast Cancer Therapy","authors":"Alaa O. Hamouda,&nbsp;Nadin H. Sarg,&nbsp;Sara I. Ibrahim,&nbsp;Rania Hamdy,&nbsp;Sameh S. M. Soliman,&nbsp;Hany A. Omar","doi":"10.1002/ardp.70064","DOIUrl":"https://doi.org/10.1002/ardp.70064","url":null,"abstract":"<div>\u0000 \u0000 <p>Polyphyllin VII (PP7), a natural saponin derived from the rhizomes of <i>Paris polyphylla</i> (family: Melanthiaceae), possesses a unique steroidal furostane structure that contributes to its versatile pharmacological profile. It is traditionally used in Chinese medicine for treating pain, insect bites, and bleeding. PP7's unique pharmacophoric features and optimal lipophilic–hydrophilic balance underlie its diverse anticancer therapeutic actions, including cell cycle arrest, apoptosis, ferroptosis, and autophagy activation, alongside metastasis and angiogenesis inhibition. PP7 has gained attention for its potent bioactivity in breast cancer and other pathological conditions. In breast cancer, PP7 demonstrates remarkable efficacy, addressing not only tumor growth but also associated complications such as inflammation and osteoporosis. Additionally, PP7 exhibits synergistic effects with chemotherapeutic agents like cisplatin, bortezomib, and gefitinib, enhancing cancer cell apoptosis and mitigating drug resistance. Beyond its anticancer properties, PP7 also displays broad pharmacological activities, including anti-inflammatory, hepatoprotective, and antimicrobial effects. Thus, PP7 holds significant potential for therapeutic application across breast cancer patients with comorbidities. However, further research is necessary to clarify its specific role in breast cancer subtypes, ensure its safety in clinical applications, and optimize its broad-scale biosynthesis. This review highlights the structure-driven mechanisms underlying PP7 actions and its therapeutic potential as a standalone agent or adjunct in breast cancer therapy.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725715","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":"5(6)-Benzoyl-Substituted Benzimidazoles and Their Benzimidazolium Salts: Design, Synthesis, Characterization, Crystal Structure, and Some Metabolic Enzymes Inhibition Properties","authors":"Aydın Aktaş,&nbsp;Eda Mehtap Özden,&nbsp;Duygu Barut Celepci,&nbsp;Tugba Taskin-Tok,&nbsp;Funda Sultan Ekti,&nbsp;İlhami Gülçin,&nbsp;Muhittin Aygün,&nbsp;Yetkin Gök,&nbsp;İlhami Çelik","doi":"10.1002/ardp.70063","DOIUrl":"https://doi.org/10.1002/ardp.70063","url":null,"abstract":"<div>\u0000 \u0000 <p>Herein, the synthesis of 1-alkyl-5(6)-benzoyl-substituted benzimidazoles and their 1,3-bisalkylbenzimidazolium halide salts are presented and evaluated for some metabolic enzyme inhibition. All compounds were characterized using various spectroscopic techniques. Single-crystal XRD analysis was performed to determine the molecular structure of two compounds. The newly synthesized compounds exhibited significant inhibitory effects against acetylcholinesterase (AChE) and human carbonic anhydrase isoforms I and II (hCA I and hCA II) enzymes. These compounds demonstrated promising inhibition profiles, with <i>K</i>_i values ranging from 12.4 ± 5.4 to 109.4 ± 49.9 nM for hCA I, 23.1 ± 11.2 to 115.0 ± 17.9 nM for hCA II, and 0.7 ± 0.3 to 4.4 ± 1.0 nM for AChE. In comparison, the reference compound acetazolamide showed <i>K</i>_i values of 30.5 ± 6.7 nM and 37.4 ± 7.8 nM against hCA I and hCA II isoenzymes, respectively. Additionally, tacrine, a known AChE inhibitor, exhibited a <i>K</i>_i value of 5.1 ± 2.7 nM. The dual inhibition of CA and AChE represents a valuable pharmacological approach with a wide range of therapeutic applications. The explanation and evaluation of the enzyme inhibition data obtained in line with the interactions of the synthesized compounds with hCA I, hCA II, and AChE enzymes were carried out by molecular docking studies. In particular, we focused on the three compounds (<b>4e</b>, <b>4f</b>, and <b>4j</b> for hCA I; <b>3g</b>, <b>4f</b>, and <b>4k</b> for hCA II; and <b>4e</b>, <b>4f</b>, <b>4j</b>, and <b>4l</b> for AChE) with the highest potential activity with each enzyme. The physicochemical, ADME, drug-likeness, medicinal chemistry, and toxicity properties of the potential ligands were then predicted so that their drug candidate suitability for further studies is revealed.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725714","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":"Recent Advances in 1,2,4-Triazole-Based Anticancer Agents: Structural Optimization, Mechanisms, and Therapeutic Potential (2022–2025)","authors":"Nafeesa Naeem,&nbsp;Ehsan Ullah Mughal,&nbsp;Amina Sadiq,&nbsp;Gehan Ahmed Othman,&nbsp;Bushra Shakoor","doi":"10.1002/ardp.70059","DOIUrl":"https://doi.org/10.1002/ardp.70059","url":null,"abstract":"<div>\u0000 \u0000 <p>The 1,2,4-triazole scaffold has emerged as a privileged heterocyclic core in the development of anticancer agents due to its unique physicochemical properties, bioavailability, and diverse biological activities. Over the past few years, significant advancements have been made in the design and structural optimization of 1,2,4-triazole-based anticancer compounds, with a strong focus on their structure–activity relationships (SARs). This review provides a comprehensive overview of the latest developments (2022–2025) in 1,2,4-triazole-containing anticancer agents, emphasizing their mechanisms of action, molecular targets, and therapeutic potential. The discussion encompasses the various modifications introduced into the 1,2,4-triazole core, exploring their impact on anticancer efficacy, selectivity, and pharmacokinetic properties. In particular, recent studies have highlighted the ability of these derivatives to inhibit key cancer-related enzymes (such as kinases, carbonic anhydrases, and topoisomerases), interfere with DNA interactions, and modulate apoptotic and autophagic pathways. This review also presents emerging SAR trends, highlighting key functional group modifications that enhance anticancer potency while minimizing off-target effects. Furthermore, recent <i>in vivo</i> studies and clinical evaluations of promising 1,2,4-triazole derivatives are discussed to assess their translational potential. Lastly, we outline future research directions and challenges in the development of next-generation triazole-based anticancer agents, aiming to bridge the gap between rational drug design and clinical application. This comprehensive analysis underscores the critical role of the 1,2,4-triazole pharmacophore in anticancer drug discovery and provides valuable insights for the design of more potent and selective anticancer therapeutics.</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":"144717000","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}