Archiv der Pharmazie最新文献_第2页

Discovery of C2: A Novel Lead Compound for the Treatment of Gout and Hyperuricemia via Multi-Pathway Inhibition 发现C2：一种通过多途径抑制治疗痛风和高尿酸血症的新型先导化合物。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-04-08 DOI: 10.1002/ardp.70234

Lina Jing, Ruoyang Miao, Chunli Zhang, Chunxia Liu

{"title":"Discovery of C2: A Novel Lead Compound for the Treatment of Gout and Hyperuricemia via Multi-Pathway Inhibition","authors":"Lina Jing, Ruoyang Miao, Chunli Zhang, Chunxia Liu","doi":"10.1002/ardp.70234","DOIUrl":"10.1002/ardp.70234","url":null,"abstract":"<div>\u0000 \u0000 Gout and hyperuricemia, prevalent metabolic disorders, are driven by elevated serum uric acid (UA) levels and subsequent monosodium urate crystal deposition, which provoke inflammatory responses and joint damage. Current therapeutic options remain unsatisfactory, underscoring the urgent need for novel agents with improved efficacy and safety profiles. In this study, we aimed to discover a new lead compound capable of concurrently addressing both hyperuricemia and associated inflammatory pain. Two novel compounds were designed and synthesized, among which C2 was identified as a promising candidate. In vitro, C2 exhibited potent dual inhibitory activity against transient receptor potential vanilloid 1 (TRPV1)—a key mediator of inflammatory pain signaling—and urate transporter 1 (URAT1), which regulated renal UA reabsorption, with IC₅₀ values of 78.52 ± 14.50 nM and 598.6 ± 115.5 nM, respectively. In vivo, oral administration of C2 (20 mg/kg) significantly reduced serum UA levels in a hyperuricemic mouse model, demonstrating efficacy comparable to dotinurad. Furthermore, in a formalin-induced inflammatory pain model, C2 produced dose-dependent antinociceptive effects. Mechanistic investigations revealed that C2 suppressed NLRP3 inflammasome activation in THP-1 cells, as indicated by reduced IL-1β secretion. Additionally, C2 ameliorated dextran sulfate sodium-induced colitis in mice, accompanied by improved histopathological scores. Collectively, these results establish C2 as a multi-target lead compound that acts simultaneously on UA transport, nociceptive signaling, and the NLRP3 inflammasome pathway, providing a strong rationale for its further development as a novel therapeutic strategy for gout and hyperuricemia.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637308","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

Beyond the Shadow of Indole: Medicinal Chemistry of Indolizines and Isoindolinones in the Fight Against Infectious Diseases 在吲哚的阴影之外：吲哚嘧啶和异吲哚酮在对抗传染病中的药物化学。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-04-08 DOI: 10.1002/ardp.70233

Mirko Pineschi, Sara Rossi, Stefania Butini, Sandra Gemma, Gabriele Carullo, Giuseppe Campiani

{"title":"Beyond the Shadow of Indole: Medicinal Chemistry of Indolizines and Isoindolinones in the Fight Against Infectious Diseases","authors":"Mirko Pineschi, Sara Rossi, Stefania Butini, Sandra Gemma, Gabriele Carullo, Giuseppe Campiani","doi":"10.1002/ardp.70233","DOIUrl":"10.1002/ardp.70233","url":null,"abstract":"<div>\u0000 \u0000 Infectious diseases remain a major global health challenge, accounting for millions of deaths annually and placing an increasing burden on healthcare systems worldwide. The rapid emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacterial strains, together with recurrent outbreaks of viral infections such as SARS-CoV-2, Ebola, Zika, Monkeypox, and influenza, underscores the urgent need for novel therapeutic agents with diverse mechanisms of action. In this context, indolizines, isoindoles, and isoindolinones represent promising scaffolds in anti-infective drug discovery due to their unique structural features, versatile reactivity, and ability to engage multiple biological targets. This review provides an updated overview of the medicinal chemistry of indolizine and isoindoles, with particular emphasis on compounds demonstrating activities against infectious pathogens. Representative examples are highlighted to illustrate structure–activity relationships (SARs), scaffold-based optimization strategies, and emerging mechanistic insights. Relevant synthetic methodologies are discussed only in the context of biologically active compounds to provide a framework for rational design. Collectively, this review underscores the therapeutic potential of indolizine- and isoindole-derived scaffolds as versatile frameworks for anti-infective drug development and highlights opportunities for further chemical and biological exploration.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637371","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

Fully Synthetic Non-Carbohydrate Heparin Mimetics-Perspectives for Therapeutic Anticoagulation and Beyond? 全合成非碳水化合物肝素模拟物-治疗抗凝及其应用前景？

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-04-01 DOI: 10.1002/ardp.70239

Katrin Nekipelov, Vito Ferro, Gerd Bendas

{"title":"Fully Synthetic Non-Carbohydrate Heparin Mimetics-Perspectives for Therapeutic Anticoagulation and Beyond?","authors":"Katrin Nekipelov, Vito Ferro, Gerd Bendas","doi":"10.1002/ardp.70239","DOIUrl":"10.1002/ardp.70239","url":null,"abstract":"Heparin is one of the oldest drugs on the market. Although clinically well established as an anticoagulant for decades, owing to its natural origin and heterogeneous glycosaminoglycan polysaccharide structure, ensuring consistent quality and reproducible biological activity remains challenging. While these facts argue against future applications of heparin in clinical routine, an increasing number of studies reveal additional potential therapeutic applications of heparin beyond its anticoagulant efficacy, that is, as an antiviral strategy or as a multi-targeted approach in oncology. Therefore, heparin appears to be a structural template for pleiotropic compounds. To combine the beneficial pleiotropic properties of heparin with improved reproducibility and safety, fully synthetic heparin mimetic substances have increasingly become a focus of scientific research. These studies enable more detailed structure-activity relationships of heparin in its interaction with proteins or diseases to be elucidated, thereby facilitating the development of novel compounds for potential therapeutic use. This review focuses in particular on fully synthetic non-carbohydrate heparin mimetic polymers with anticoagulant activities, as well as their properties beyond anticoagulation. Advances in the development of such mimetics, especially over the past decade, allow increasingly robust conclusions to be drawn regarding their efficacy and contribute to a deeper understanding of this class of compounds.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 4","pages":"e70239"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147696932","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

Design, Synthesis and Evaluation of Anticancer Potential of Novel Pyrrolopyrazines Against Glioblastoma: Mechanistic Details and In Vivo Safety Analysis. 新型吡咯吡嗪类药物抗胶质母细胞瘤抗癌潜力的设计、合成和评价：机制细节和体内安全性分析。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-04-01 DOI: 10.1002/ardp.70241

Ayşe Usta, Burak Kuzu, Meltem Tan-Uygun, Veysel Yüksek, M Edip Akyol, Nurettin Menges

{"title":"Design, Synthesis and Evaluation of Anticancer Potential of Novel Pyrrolopyrazines Against Glioblastoma: Mechanistic Details and In Vivo Safety Analysis.","authors":"Ayşe Usta, Burak Kuzu, Meltem Tan-Uygun, Veysel Yüksek, M Edip Akyol, Nurettin Menges","doi":"10.1002/ardp.70241","DOIUrl":"10.1002/ardp.70241","url":null,"abstract":"A protocol through propargyl moiety on pyrrole ring cyclization with ammonium acetate was demonstrated. With this protocol, 11 pyrrolo[1,2-a]pyrazine derivatives were synthesized, and their antiproliferative activity against the U87MG glioblastoma cell line was evaluated. Among the synthesized compounds, a naphthyl-substituted derivative (3g) exhibited the most potent in vitro activity with an IC50 value of 60 µM, and showed no antiproliferative effect against human dermal fibroblast (HDF) cells up to 100 μM. Gene expression analysis of U87MG cells treated with 3g revealed a significant upregulation of key genes involved in apoptosis (CASP8, CASP9, CASP3, BAX, BCL2), autophagy (ATG3, ATG5), necroptosis (RIPK1), and DNA damage repair (PARP1) suggesting a multifaceted cell death mechanism. Furthermore, the in vivo safety profile of compound 3g was assessed in an animal model by evaluating renal (BUN, creatinine) and hepatic (AST, ALT, ALP) biochemical parameters. No significant adverse effects on renal function were observed across the tested doses (IC50, IC50 × 2, and IC50 × 3). While AST and ALT levels remained stable, ALP levels showed a dose-dependent modulation. These findings highlight the potential of 3g as a promising anticancer agent for glioblastoma, warranting further investigation into its detailed mechanisms of action and long-term safety.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 4","pages":"e70241"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147696938","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

Effects of Supramolecular Interactions on E/Z-Isomerizations in Water and Their Importance for Biological Applications. 超分子相互作用对水中E/ z异构化的影响及其在生物应用中的重要性。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-04-01 DOI: 10.1002/ardp.70242

Doğan Akbulut, Gianna Pölderl, Line Næsborg

引用次数: 0

Ecofriendly Synthesis of New Azo Compounds as Antibacterial Agents: In Vitro Screening and Preliminary In Vivo Evaluation Using ¹³¹I-Radiolabeling. 新型偶氮抗菌化合物的生态合成：体外筛选及131i放射性标记的初步体内评价。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-04-01 DOI: 10.1002/ardp.70245

Kurls E Anwer, Basma M Essa, Adli A Selim, Galal H Sayed, Safaa S Shaban

{"title":"Ecofriendly Synthesis of New Azo Compounds as Antibacterial Agents: In Vitro Screening and Preliminary In Vivo Evaluation Using 131I-Radiolabeling.","authors":"Kurls E Anwer, Basma M Essa, Adli A Selim, Galal H Sayed, Safaa S Shaban","doi":"10.1002/ardp.70245","DOIUrl":"https://doi.org/10.1002/ardp.70245","url":null,"abstract":"This work is designed to establish sustainable routes for the synthesis of new variable azo heterocyclic derivatives via the reaction of 2-[(dicyanomethyl)diazinyl]benzoic acid 2 with different nucleophilic agents, including hydrazine derivatives (such as phenyl hydrazine and 2,4-dinitrophenylhydrazine), acylhydrazines (e.g., benzoylhydrazine), nitrogen-based nucleophiles (semicarbazide and thiosemicarbazide), oxygen-containing reagents (hydroxylamine), as well as urea, thiourea, guanidine hydrochloride, and o-phenylenediamine. Both conventional heating and microwave approaches were used to furnish the desired heterocycles. The compounds exhibited potent antibacterial activity against Gram-positive and Gram-negative pathogens, outperforming fluconazole. The lead compound was successfully radiolabeled with 131I in high yield (87.72% RCY). In vivo evaluation in an infection model demonstrated excellent pharmacokinetics, with specific uptake in infected tissue (13.7% ID/g at 1 h) and a high target-to-non-target ratio (6.31). These findings underscore the theranostic potential of these azo compounds, positioning them as both antimicrobial agents and candidate radiotherapeutics for infection.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 4","pages":"e70245"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721236","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

Indoles-A Targeting the PI3K/Akt/mTOR Pathway: Recent Advances in Strategic Design, Mechanism, and Future Perspectives. 靶向PI3K/Akt/mTOR通路的吲哚- a：策略设计、机制和未来展望的最新进展。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-04-01 DOI: 10.1002/ardp.70244

Harish Chandra Vishwakarma, Jayalakshmi Bahuleyan, Mohamed A Abdelgawad, Izzeddin Alsalahat, Mohammed Elmowafy, Ayman Salama, Sunil Kumar, Bijo Mathew

{"title":"Indoles-A Targeting the PI3K/Akt/mTOR Pathway: Recent Advances in Strategic Design, Mechanism, and Future Perspectives.","authors":"Harish Chandra Vishwakarma, Jayalakshmi Bahuleyan, Mohamed A Abdelgawad, Izzeddin Alsalahat, Mohammed Elmowafy, Ayman Salama, Sunil Kumar, Bijo Mathew","doi":"10.1002/ardp.70244","DOIUrl":"https://doi.org/10.1002/ardp.70244","url":null,"abstract":"Indole derivatives are known to be a diverse group of compounds that are potentially useful in the quest for new anticancer agents, especially because of their ability to regulate important cellular signaling pathways involved in cancer development. Of these, the PI3K/Akt/mTOR pathway is a dominant regulator of cell growth, proliferation, metabolism, and survival. Their dysregulation is seen in a broad range of cancers. The structural features of the indole scaffold make it possible to design potent derivatives. These are selective for the PI3K/Akt/mTOR pathway, with potential for greater specificity and lower toxicity than traditional treatments. This review critically assesses recent developments in the design, synthesis, and biological activity of indole-derived molecules as anticancer drugs, focusing on their modes of action, such as kinase inhibition and induction of apoptosis. Emphasizing natural and synthetic indole derivatives, the report covers their cytotoxic activity on different cancer cell lines and describes structure-activity relationships for further drug development. This review presents both traditional and novel synthetic approaches that demonstrate the chemical flexibility of the indole unit. Together, these results point out the advantages of indole derivatives as multitarget drugs for the treatment of cancer, in part through disruption of the PI3K/Akt/mTOR pathway, and suggest directions for future investigation as precision drugs in cancer therapy.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 4","pages":"e70244"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758090","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

Indole-Based Curcumin Analogs With Antioxidant and Antitumor Activities: Synthesis, Molecular Docking 具有抗氧化和抗肿瘤活性的吲哚基姜黄素类似物：合成、分子对接。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-03-24 DOI: 10.1002/ardp.70228

Zhipeng Huang, Shuzhao Wang, Rongming Yu, Zhicheng Li, Gangchun Sun

{"title":"Indole-Based Curcumin Analogs With Antioxidant and Antitumor Activities: Synthesis, Molecular Docking","authors":"Zhipeng Huang, Shuzhao Wang, Rongming Yu, Zhicheng Li, Gangchun Sun","doi":"10.1002/ardp.70228","DOIUrl":"10.1002/ardp.70228","url":null,"abstract":"<div>\u0000 \u0000 Curcumin, a natural compound with broad pharmacological effects, suffers from low bioavailability due to its unstable β-diketone structure. To address this, we designed novel indole-based curcumin analogs via molecular hybridization, replacing the β-diketone with a monocarbonyl bridge to enhance stability. A series of symmetric (1a and 1b) and asymmetric (3a–3i) compounds were synthesized. The antioxidant assays (DPPH method) revealed a concentration-dependent radical scavenging effect, with compound 3e exhibiting 23.1% inhibition at 64 μM. In vitro antitumor screening using the MTT assay across four human cancer cell lines (Eca109, SMMC7721, A549, and MGC803) revealed promising inhibitory effects. Among them, compound 1a displayed the most potent activity against Eca109 cells, with an IC50 value of 6.84 μM, being markedly lower than those of curcumin (29.5 μM) and cisplatin (10.4 μM), indicating superior cytotoxicity. Molecular docking analysis of 1a predicted strong binding to EGFR (–10.9 kcal/mol) and CDK6 (–11.2 kcal/mol), stabilized by hydrogen bonds and hydrophobic interactions. These results validate the novelty of indole modification and correlate in vitro activity with in silico mechanisms.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508185","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

Ferroptosis-Driven Anticancer Activity of 1,3,4-Oxadiazole–Benzimidazole/Acetamide Hybrids: Design, Synthesis, and Biological Profiling 1,3,4-恶二唑-苯并咪唑/乙酰胺杂合体的抗癌活性：设计、合成和生物学分析。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-03-24 DOI: 10.1002/ardp.70229

Fatma Fouad Hagar, Amer Ali Abd El-Hafeez, Samar H. Abbas, Ahmed M. Sayed, Asim Abdelfattah, Heba S. Abd-Ellah, Dalia Abdelhamid, Mohamed Abdel-Aziz

{"title":"Ferroptosis-Driven Anticancer Activity of 1,3,4-Oxadiazole–Benzimidazole/Acetamide Hybrids: Design, Synthesis, and Biological Profiling","authors":"Fatma Fouad Hagar, Amer Ali Abd El-Hafeez, Samar H. Abbas, Ahmed M. Sayed, Asim Abdelfattah, Heba S. Abd-Ellah, Dalia Abdelhamid, Mohamed Abdel-Aziz","doi":"10.1002/ardp.70229","DOIUrl":"10.1002/ardp.70229","url":null,"abstract":"<div>\u0000 \u0000 A series of 1,3,4-oxadiazole-benzimidazole/acetamide derivatives (7a–r) was designed, synthesized, and evaluated for their anticancer activity. NCI-screening results at 10 µM against the 60 human tumor cell line panel revealed a broad-spectrum of antiproliferative effects of the tested compounds. Compounds 7b, 7e, 7f, 7g, 7h, 7k, 7l, and 7r were further tested in a five-dose assay, and they exhibited half-maximal growth inhibitory (GI50) values ranging from 0.90 to 43.50 µM. Focused studies in MDA-MB-231 triple-negative breast cancer (TNBC) cells demonstrated that compounds 7b, 7g, 7h, 7k, and 7l possessed potent antiproliferative activity, with half-maximal inhibitory concentration (IC50) values between 1.92 and 3.69 µM. Mechanistic investigations using cell death pathway inhibitors indicated that compounds 7b, 7k, and 7l did not induce necrosis, apoptosis, or autophagy. Instead, these compounds significantly increased intracellular ferrous iron (Fe2+) and malondialdehyde (MDA) levels and induced lipid peroxidation in MDA-MB-231 cells. In parallel, GPX4 expression was markedly reduced at both the mRNA and protein levels, supporting ferroptosis as the primary mechanism of action. In addition, molecular docking studies and molecular dynamics simulations were performed for derivatives 7b, 7k, and 7l in order to confirm the mechanistic study. Collectively, these findings suggest that the 1,3,4-oxadiazole–benzimidazole/acetamide scaffold represents a promising chemotype for developing ferroptosis-inducing therapeutics targeting TNBC.\u0000 </div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508197","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

Evaluation of Amikacin Mediated Platelet Aggregate Dissociation in Multi-Anticoagulant-Dependent Pseudothrombocytopenia (PTCP) 多重抗凝药物依赖性假性血小板减少症（PTCP）中阿米卡星介导的血小板聚集解离的评价。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-03-23 DOI: 10.1002/ardp.70230

Bo Wang, Junwen Liu, Wenying Yao, Shulin Ruan, Yunxia Xu, Zhengrong Zhong

{"title":"Evaluation of Amikacin Mediated Platelet Aggregate Dissociation in Multi-Anticoagulant-Dependent Pseudothrombocytopenia (PTCP)","authors":"Bo Wang, Junwen Liu, Wenying Yao, Shulin Ruan, Yunxia Xu, Zhengrong Zhong","doi":"10.1002/ardp.70230","DOIUrl":"10.1002/ardp.70230","url":null,"abstract":"<div>\u0000 \u0000 Anticoagulant-dependent pseudothrombocytopenia (PTCP) is an in vitro artifact that leads to falsely low platelet counts. To evaluate the efficacy of Amikacin in reversing platelet (PLT) clumping induced by various anticoagulants, including EDTA, heparin, and sodium citrate. we collected 26 blood samples demonstrating EDTA-dependent pseudothrombocytopenia. Amikacin solution (50 μL of 50 mg/L) was added to 500 μL of whole blood from each sample. Complete blood count (CBC) analysis was performed at 5, 30, 60, 240 min, and 24 h post-treatment. Additionally, five samples exhibiting PLT aggregation dependent on multiple anticoagulants (EDTA, heparin, and sodium citrate) were treated with Amikacin, and PLT counts were compared across the different anticoagulant tubes. For the Amikacin-treated EDTA tubes, differential leukocyte counts (DLC) were analyzed and compared with untreated controls, with validation by flow cytometry. Amikacin treatment significantly increased PLT counts in EDTA-dependent samples compared with untreated controls (p < 0.001), with the maximum effect observed at 240 min. In samples with multi-anticoagulant dependency, PLT counts in heparin- and sodium citrate-anticoagulated tubes remained significantly lower than those in EDTA tubes after Amikacin treatment (p < 0.01). Furthermore, in Amikacin-treated EDTA blood, the proportions of neutrophils and basophils were significantly increased (p < 0.0001), whereas the proportions of lymphocytes and monocytes decreased (p < 0.01). Amikacin effectively reverses EDTA-dependent PLT clumping within 240 min, but only partially resolves aggregation induced by heparin or sodium citrate. Moreover, the use of Amikacin in EDTA-anticoagulated blood compromises the accuracy of CBC differential counts, rendering such samples unsuitable for routine hematological analysis.\u0000 </div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502603","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