Archiv der Pharmazie最新文献_第7页

A Proteochemometric Model for Ligands of the SLC5 Transporter Family SLC5转运蛋白家族配体的蛋白质化学计量学模型。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-01-16 DOI: 10.1002/ardp.70183

Martin Juhás, Gerhard Ecker

引用次数: 0

Deciphering Anticoagulant Active Substances and Mechanisms in Guanxinjing Formula Through Phenotype-Anchored Hierarchical Strategy and Topological Network Analysis 通过表型锚定层次策略和拓扑网络分析解读冠心静方抗凝血活性物质及其作用机制。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-01-10 DOI: 10.1002/ardp.70181

Yuanlin Luo, Xiaozhuan Jia, Hai Ren, Yue Zhu, Can Ren, Jiao Zhao, Heng Xu, Yi Wang, Lu Zhao, Zhenzhong Yang

{"title":"Deciphering Anticoagulant Active Substances and Mechanisms in Guanxinjing Formula Through Phenotype-Anchored Hierarchical Strategy and Topological Network Analysis","authors":"Yuanlin Luo, Xiaozhuan Jia, Hai Ren, Yue Zhu, Can Ren, Jiao Zhao, Heng Xu, Yi Wang, Lu Zhao, Zhenzhong Yang","doi":"10.1002/ardp.70181","DOIUrl":"10.1002/ardp.70181","url":null,"abstract":"<div>\u0000 \u0000 <p>Anticoagulation is the cornerstone for preventing thrombosis in coronary heart disease patients with atrial fibrillation or a mechanical heart valve. Guanxinjing formula (GXJF) demonstrates anticoagulant effects, while its anticoagulant substances and mechanisms remain unclear. In this study, the chemical composition of GXJF was identified, establishing a chemical basis for the discovery of anticoagulant substances. Then, a phenotype-anchored hierarchical strategy (the formula, the medicinal materials, and the representative compounds) was developed to reveal active substances, especially synergy. Meanwhile, phenotype-based topological network analysis was employed to delineate the pivotal targets. Dynamic blood flow imaging analysis in zebrafish was used to evaluate the effect of active substances in vivo. This approach enables rapid identification of active substances by hierarchically eliminating interference from inactive components, uncovers potential synergistic effects, and accelerates target identification by focusing on phenotype-relevant protein networks. Pentagalloylglucose, (+)-catechin, senkyunolide A, and lithospermic acid were considered as the anticoagulant substances of GXJF. Notably, synergy between hydroxysafflor yellow A and anhydrosafflor yellow B were discovered. Topological network analysis and enzyme activity assays suggested that they exert anticoagulant effects by inhibiting coagulation factors Xa and Ⅱa. These findings provide support for the clinical application of GXJF and establish a foundation for its quality control.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948182","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}

引用次数: 0

New Quinoline Kinase Inhibitors With Good Selectivity for NAK Kinases and Anti-Tumor Activity Against Ewing Sarcoma 新型喹啉激酶抑制剂对NAK激酶具有良好的选择性和抗尤文氏肉瘤的肿瘤活性。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-01-10 DOI: 10.1002/ardp.70184

Caroline de Bem Gentz, Thais Helena Maciel Fernandes, Marcela Silva Lopes, Lewis Elson, Andreas Krämer, Lucas Rodrigo de Souza, Isadora Serraglio Fortes, Geórgia Silva Pinto, Martha Cestari Silva Martins, Henrique Barros de Lima, André da Silva Santiago, Lauro José Gregianin, Katlin Brauer Massirer, Mário Henrique Bengtson, Rafael Roesler, Stefan Knapp, Stefan A. Laufer, Saulo Fernandes de Andrade

{"title":"New Quinoline Kinase Inhibitors With Good Selectivity for NAK Kinases and Anti-Tumor Activity Against Ewing Sarcoma","authors":"Caroline de Bem Gentz, Thais Helena Maciel Fernandes, Marcela Silva Lopes, Lewis Elson, Andreas Krämer, Lucas Rodrigo de Souza, Isadora Serraglio Fortes, Geórgia Silva Pinto, Martha Cestari Silva Martins, Henrique Barros de Lima, André da Silva Santiago, Lauro José Gregianin, Katlin Brauer Massirer, Mário Henrique Bengtson, Rafael Roesler, Stefan Knapp, Stefan A. Laufer, Saulo Fernandes de Andrade","doi":"10.1002/ardp.70184","DOIUrl":"10.1002/ardp.70184","url":null,"abstract":"<p>In the past few years, several novel anticancer agents targeting protein kinases have been discovered expanding the available therapeutic arsenal. However, few new therapeutic approaches have been developed for the treatment of childhood cancer. To this end, we have been making efforts to contribute to this important field. Herein, we identified a series of new 4,6-disubstituted quinoline derivatives from our in-house quinoline chemical library that showed promising anti-proliferative activity against Ewing Sarcoma (ES). This interesting observation engaged us to further investigate these derivatives since this type of cancer is among the most common bone cancers in children. Evaluation of the quinoline derivatives against a panel of kinases demonstrated generally narrow selectivity profiles of this compound class. Interestingly, the main kinases that were inhibited belonged to the NAK family of kinases, in particular, the family member cyclin G-associated kinase (GAK) which was inhibited at nanomolar range in enzyme kinetic assays.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948249","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}

引用次数: 0

Exploring Sulfonamides: Biological Activities and Structure–Activity Relationships 探索磺胺类：生物活性和构效关系。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-01-08 DOI: 10.1002/ardp.70180

Souad Zerbib, Natália Cruz-Martins, Latifa Bouissane

引用次数: 0

Erratum: Support Vector Machine Identification of Small Molecule Binders to an Understudied Allosteric Site of SARS-CoV-2 Mpro for Next-Generation PROTAC-Based Therapeutics 支持向量机识别新一代基于protac的治疗方法中未充分研究的SARS-CoV-2 Mpro变结构位点的小分子结合物。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-01-07 DOI: 10.1002/ardp.70182

引用次数: 0

Issue Information: Arch Pharm (1/2026) 发行资料：Arch Pharm （1/2026）

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-01-01 DOI: 10.1002/ardp.70185

引用次数: 0

Current Scenario of Hydroxamic Acid Derivatives With In Vivo Antitumor Therapeutic Potential 具有体内抗肿瘤治疗潜力的羟肟酸衍生物的现状。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-12-28 DOI: 10.1002/ardp.70178

Zhi Xu, Junna Liu

{"title":"Current Scenario of Hydroxamic Acid Derivatives With In Vivo Antitumor Therapeutic Potential","authors":"Zhi Xu, Junna Liu","doi":"10.1002/ardp.70178","DOIUrl":"10.1002/ardp.70178","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer, as a fatal metastatic disease, exerts a deep-seated and extensive influence on human health, impacting not just the physical condition of patients but also their psychological state and social lives. Hydroxamic acid derivatives, as exceptional histone deacetylase (HDAC) inhibitors, could regulate diverse cellular pathways, cause cell cycle arrest, and promote programmed cell death. Consequently, hydroxamic acid derivatives demonstrate significant efficacy in combating a wide range of cancers, including hematological malignancies and solid tumors. Moreover, diverse hydroxamic acid derivatives have already been applied in clinics or are currently undergoing clinical trials for cancer therapy, revealing that hydroxamic acid derivatives hold great promise as scaffolds for exploring novel anticancer agents. This review aims to comprehensively summarize the current scenario of hydroxamic acid derivatives with in vivo antitumor therapeutic potential, along with their metabolic profiles, pharmacokinetic properties, toxicity, and mechanisms of action, developed since 2020, to facilitate further rational design of safer and more potent candidates.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848424","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}

引用次数: 0

Carboline Hybrids as Potential Multitarget-Directed Anti-Alzheimer's Disease Agents: A Comprehensive Analysis of Design Strategies and Structure–Activity Relationships Carboline杂种作为潜在的多靶点定向抗阿尔茨海默病药物：设计策略和构效关系的综合分析。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-12-28 DOI: 10.1002/ardp.70166

Sandipan Dash, Arghya Kusum Dhar

{"title":"Carboline Hybrids as Potential Multitarget-Directed Anti-Alzheimer's Disease Agents: A Comprehensive Analysis of Design Strategies and Structure–Activity Relationships","authors":"Sandipan Dash, Arghya Kusum Dhar","doi":"10.1002/ardp.70166","DOIUrl":"10.1002/ardp.70166","url":null,"abstract":"<div>\u0000 \u0000 <p>The β-carboline hybrids represent innovative therapeutics for Alzheimer's disease (AD) as multitarget-directed ligands (MTDLs), addressing cholinergic deficits through AChE/BuChE inhibition, amyloid-β (Aβ) aggregation, tau hyperphosphorylation via GSK-3β/DYRK1A suppression, neuroinflammation and oxidative stress. Structure–activity relationships (SARs) indicate that fluorine enhances BuChE selectivity through Tyr128 hydrogen bonding, hydrophobic extensions (α-naphthyl substituted β-carboline) optimise Aβ disaggregation and C4-8 spacers (piperazine-linked bivalent β-carboline) facilitate dual-target engagement without compromising blood–brain barrier permeability. Validated pharmacophore models prioritise planar cores for π–stacking, cationic centres for AChE/NMDA targeting and flexible linkers, positioning these hybrids as clinically translatable, disease-modifying candidates. In this extensive review, we summarised the derivatives and hybrids of carboline over the past decade for managing AD. We focus on their design, pharmacological activity and SAR analysis, as well as an exclusive pharmacophore model for both single- and multitarget carboline derivatives. We hope this review enhances the reader's understanding of future exploratory options for carboline hybrids in AD management.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848514","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}

引用次数: 0

Targeting TXNIP With Saroglitazar Mitigates Acute Hepatic Injury in Rats Challenged With Thioacetamide: A Multistep Computational and Experimental Approach 沙格列他靶向TXNIP减轻硫乙酰胺致大鼠急性肝损伤：一种多步骤计算和实验方法

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-12-28 DOI: 10.1002/ardp.70179

Fatma Elnaghy, Sameh Saber, Eman M. Abd El-Kader, Mohammad A. Elmorsy, George S. G. Shehatou

{"title":"Targeting TXNIP With Saroglitazar Mitigates Acute Hepatic Injury in Rats Challenged With Thioacetamide: A Multistep Computational and Experimental Approach","authors":"Fatma Elnaghy, Sameh Saber, Eman M. Abd El-Kader, Mohammad A. Elmorsy, George S. G. Shehatou","doi":"10.1002/ardp.70179","DOIUrl":"10.1002/ardp.70179","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute hepatic injury (AHI) is a sudden onset of hepatic inflammation, a key contributor to the progression of diabetes and other disorders. Diabetes mellitus also increases the risk of liver illnesses associated with inflammatory disorders. According to recent studies, Saroglitazar (SAR), originally developed for the treatment of hyperglycemia and dyslipidemia, has also demonstrated notable anti-inflammatory properties. In our search for a prime therapeutic approach for inflammatory liver disorders in diabetic patients, we investigated the effects of SAR on thioacetamide (TAA)-induced AHI in rats. In order to investigate possible interactions between SAR and thioredoxin-interacting protein (TXNIP), this research utilized a multistep methodology that included prediction of computational targets, network analysis, molecular docking, and experimental verification. Findings revealed the anti-inflammatory potential of SAR, presumably ascribed to its inhibition of the NLRP3 signaling pathway by inhibiting TXNIP, an NLRP3 inflammasome upstream regulator. Furthermore, SAR inhibited the priming signal brought on by NFκB stimulation and the succeeding inflammasome components, cleaved caspase-1, GSDMD, IL-1β, and IL-18. As a result, SAR demonstrated anti-pyroptotic properties in the injured liver. Moreover, SAR exhibited potential antiapoptotic effects, as indicated by decreased Bax levels, decreased tissue expression of cleaved caspase-3, and increased BCL2 levels. Improvements in liver function, oxidative stress markers, liver histology, and the liver weight-to-body weight ratio all supported these findings. In conclusion, SAR demonstrates potential as a preventive treatment for inflammatory liver disorders. To render these preclinical findings into efficient techniques for enhancing hepatic function, more research is required, particularly in the context of diabetes.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848502","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}

引用次数: 0

Tetrazole Derivatives as Multiclass Inhibitors of Bacterial Carbonic Anhydrases 四唑衍生物作为细菌碳酸酐酶的多类抑制剂。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-12-26 DOI: 10.1002/ardp.70177

Andrea Ammara, Simone Giovannuzzi, Viviana De Luca, Clemente Capasso, Alessio Nocentini, Claudiu T. Supuran, Paola Gratteri

{"title":"Tetrazole Derivatives as Multiclass Inhibitors of Bacterial Carbonic Anhydrases","authors":"Andrea Ammara, Simone Giovannuzzi, Viviana De Luca, Clemente Capasso, Alessio Nocentini, Claudiu T. Supuran, Paola Gratteri","doi":"10.1002/ardp.70177","DOIUrl":"10.1002/ardp.70177","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigates derivatives including a tetrazole zinc-binding group as inhibitors of the α-, β-, and γ-class carbonic anhydrase (CA) isoforms from pathogenic bacteria such as <i>Vibrio cholerae</i>, <i>Escherichia coli</i>, and <i>Streptococcus mutans</i>. A library of 22 previously synthesized compounds was evaluated for their inhibitory activity against bacterial CAs using a stopped-flow CO<sub>2</sub> hydrase assay. The tetrazole-based inhibitors displayed marked activity toward bacterial α- and β-class CAs, with inhibition constants (<i>K</i><sub>I</sub>s) ranging from 0.43 to 18.7 µM. Among them, <b>2i</b> and <b>2p</b> emerged as two of the most potent inhibitors. Selectivity studies showed that only a few compounds exhibited moderate (10- to 20-fold) selectivity for bacterial β-CAs over human CA I, with limited selectivity against human CA II. Molecular modelling studies of the most representative compounds elucidated the key interactions responsible for their potency and selectivity, in agreement with experimental findings. Overall, these results highlight tetrazole derivatives as promising scaffolds for the development of novel antibacterial CA inhibitors.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831822","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}

引用次数: 0