Archiv der Pharmazie最新文献

{"title":"The Potential of Resveratrol as an Anticancer Agent: Updated Overview of Mechanisms, Applications, and Perspectives","authors":"Md Rezaul Islam,&nbsp;Rahaf Ajaj,&nbsp;Abdur Rauf,&nbsp;Sanzida Sharmin Shanta,&nbsp;Md Ibrahim Khalil Al-Imran,&nbsp;Md Naeem Hossain Fakir,&nbsp;Alessandra Gianoncelli,&nbsp;Giovanni Ribaudo","doi":"10.1002/ardp.70109","DOIUrl":"10.1002/ardp.70109","url":null,"abstract":"<div>\u0000 \u0000 <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></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-29","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":"Targeting JNK1/2 and P38 Mitogen-Activated Protein Kinases With Pazopanib Mitigates Bleomycin-Induced Lung Fibrosis","authors":"Rasha Abdelhady,&nbsp;Rabab H. Sayed,&nbsp;Nancy S. Younis,&nbsp;Omaima Ali,&nbsp;Mai Abdallah Elhemely,&nbsp;Ahmed M. Ashour,&nbsp;Shuruq E. Alsufyani,&nbsp;Hany H. Arab,&nbsp;Mohammed S. Abdel-Hamid","doi":"10.1002/ardp.70105","DOIUrl":"10.1002/ardp.70105","url":null,"abstract":"<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 (<i>n</i> = 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":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-28","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 Role of the AMY1 Receptor Signaling Cascade in the Protective Effect of Sulforaphane Against Nitroglycerin-Induced Migraine in Mice","authors":"Luejine A. Elbendary,&nbsp;Ghada A. Abdel-Latif,&nbsp;Mohamed A. Khattab,&nbsp;Ayman E. El-Sahar,&nbsp;Rabab H. Sayed","doi":"10.1002/ardp.70107","DOIUrl":"10.1002/ardp.70107","url":null,"abstract":"<div>\u0000 \u0000 <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></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-28","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,&nbsp;Hazem Elkady,&nbsp;Hazem A. Mahdy,&nbsp;Bshra A. Alsfouk,&nbsp;Dalal Z. Husein,&nbsp;Fatma G. Amin,&nbsp;Abdelrahman A. Abuelkhir,&nbsp;Eslam B. Elkaeed,&nbsp;Ahmed M. Metwaly,&nbsp;Ibrahim H. Eissa","doi":"10.1002/ardp.70097","DOIUrl":"10.1002/ardp.70097","url":null,"abstract":"<div>\u0000 \u0000 <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, <b>7b</b> 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 <b>7b</b>, featuring a unique structural assembly of a 2,3-dihydro-1,3,4-thiadiazole core, a <i>para</i>-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 <b>7b</b> induces G1-phase cell-cycle arrest and promotes apoptosis through the upregulation of BAX, caspases-8/9, and downregulation of Bcl-2. Compound <b>7b</b> also inhibited cell migration in wound-healing assays. Structure–activity relationship (SAR) analysis indicated that <i>para</i>-substituted electron-donating groups enhanced cytotoxic potency. Molecular docking and molecular dynamics simulations confirmed the stable binding of <b>7b</b> 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 <b>7b</b> is a promising lead for further development as a selective dual kinase inhibitor for breast cancer therapy.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-28","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,&nbsp;Shireen Mona Dutt,&nbsp;Suraj N. Mali,&nbsp;Erica Vigiani,&nbsp;Julie Pelletier,&nbsp;Jean Sévigny,&nbsp;Shailesh S. Gurav,&nbsp;Rahul D. Jawarkar,&nbsp;Abdulraheem SA Almalki,&nbsp;Muhammad Safwan Akram,&nbsp;Zahra Batool,&nbsp;Silvia Schenone,&nbsp;Jamshed Iqbal,&nbsp;Zahid Shafiq","doi":"10.1002/ardp.70098","DOIUrl":"10.1002/ardp.70098","url":null,"abstract":"<div>\u0000 \u0000 <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 <b>7(a–s)</b>. 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></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-28","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,&nbsp;Kseniya N. Sedenkova,&nbsp;Polina А. Kovaleva,&nbsp;Anton S. Shakhov,&nbsp;Anatoly A. Kotlobay,&nbsp;Elena B. Averina,&nbsp;Irina B. Alieva","doi":"10.1002/ardp.70104","DOIUrl":"10.1002/ardp.70104","url":null,"abstract":"<div>\u0000 \u0000 <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></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-28","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}

{"title":"Ultra-Fast Green UPLC-MS/MS Method for the Quantification of Cediranib in the Human Liver Microsome Matrix: In Vitro and In Silico Metabolic Stability Assessment","authors":"Mohamed W. Attwa,&nbsp;Ali S. Abdelhameed,&nbsp;Adnan A. Kadi","doi":"10.1002/ardp.70111","DOIUrl":"https://doi.org/10.1002/ardp.70111","url":null,"abstract":"<div>\u0000 \u0000 <p>Cediranib (AZD2171; CDB) is an oral pan-VEGF receptor tyrosine kinase inhibitor and a potent antiangiogenic agent. This study sought to develop a precise, rapid, dependable, and sustainable UPLC-MS/MS approach for measuring CDB in the human liver microsome (HLM) matrix, utilized for assessing the CDB metabolic stability inside this matrix. The validation processes for the UPLC-MS/MS system adhered to US-FDA rules for bioanalytical technique validation. The validated method utilized the HLM matrix throughout a level range of 1–4000 ng/mL with a duration of 1 min on UPLC-MS/MS instrumentation. The precision (%RSD) and accuracy (%E) rates for intraday and interday measurements varied from −1.41% to 8.0% and from −2.75% to 9.67%, respectively. The StarDrop software employed P450 and DEREK modules to evaluate metabolic lability and to characterize CDB structural warnings, respectively. The in vitro <i>t</i>_1/2 was determined to be 25.48 min, and the CDB intrinsic clearance was determined to be 31.82 mL/min/kg. In silico assessments indicate that slight structural modifications to the pyrrolidine moiety (61%), methyl group (32%), and the propyl group (7%) in drug design could increase the CDB metabolic stability. The assessment of in silico CDB ADME characteristics and metabolic stability is fundamental for progressing innovative drug research focused on augmenting metabolic stability.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146859","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":"Loading of Dicarboxylatoplatinum(II)-NHC Complexes in Bacterial Ghosts as an Advanced Development in Cancer Therapy","authors":"Amelie Scherfler,&nbsp;Klaus Wurst,&nbsp;Stefan Schwaiger,&nbsp;Francesco Baschieri,&nbsp;Martin Hermann,&nbsp;Daniel Baecker,&nbsp;Irena Pashkunova-Martic,&nbsp;Brigitte Kircher,&nbsp;Hristo P. Varbanov","doi":"10.1002/ardp.70108","DOIUrl":"https://doi.org/10.1002/ardp.70108","url":null,"abstract":"<p>This study aimed to improve the drug-like properties of benzimidazole-based Pt(II)-N-heterocyclic carbene (NHC) complexes, particularly by enhancing their water solubility and delivery to cancer cells. Accordingly, four new Pt(II) complexes of the benzimidazol-2-ylidene type, featuring monodentate carboxylato ligands, were prepared and their structures confirmed through a combination of spectroscopic and crystallographic techniques. Their stability in aqueous solution and cell culture medium was investigated by ¹H NMR spectroscopy and HPLC-MS analysis. Cytotoxicity was assessed using the MTT assay in ovarian cancer cell lines (A2780wt (cisplatin sensitive) and A2780cis (cisplatin resistant)) and a noncancerous bone marrow stromal cell line (HS-5). Most complexes exhibited cytotoxicity comparable to or exceeding that of carboplatin, with preferential activity toward cancer cells. Loading of all four Pt(II) complexes into bacterial ghost cells (BGs) derived from two different nonpathogenic bacterial strains, <i>Escherichia coli (E. coli)</i> Nissle 1917 and <i>E. coli</i> NM522 notably enhanced the intracellular accumulation and cytotoxicity. Furthermore, mechanistic studies demonstrated that all tested compounds, regardless of formulation, induced apoptosis. Their potential to trigger immunogenic cell death was also evaluated, though only a modest effect was observed on selected hallmarks. Collectively, these findings highlight the potential of dicarboxylatoplatinum(II)-NHC complexes, particularly loaded into BG-based formulations, as promising anticancer drug candidates.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146861","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":"Structural Advances in Non-Sulfonamide Carbonic Anhydrase Inhibitors: Insights Into Design, Bioactivity, and Binding Mechanism","authors":"Mahmood Ahmed,&nbsp;Muhammad Zaeem Mehdi,&nbsp;Mehwish Javed,&nbsp;Mohammed H. AL Mughram,&nbsp;Masooma Irfan,&nbsp;Ahmad Saeed,&nbsp;Ali Abbas Aslam","doi":"10.1002/ardp.70090","DOIUrl":"10.1002/ardp.70090","url":null,"abstract":"<div>\u0000 \u0000 <p>Carbonic anhydrases (CAs) belong to a set of metalloenzymes that facilitate the reversible catalytic hydration of CO₂, playing crucial roles in pH regulation, respiration, and electrolyte secretion. Dysregulation of specific CA isoforms, particularly the human variants hCA I, II, IX, and XII, is implicated in multiple pathological conditions, including glaucoma, epilepsy, obesity, and various cancers. Traditionally, sulfonamide-based inhibitors have dominated the therapeutic landscape; however, their limitations, such as off-target side effects, poor selectivity for different isoforms, and allergic reactions, have galvanized interest in alternative scaffolds. This comprehensive review critically examines the burgeoning class of non-sulfonamide inhibitors targeting hCA isoforms, focusing on the chemical diversity, binding mechanisms, and structure–activity relationships of recently developed phenols, carboxylic acids, coumarins, dithiocarbamates, and polyamines. Special attention is given to the advances in X-ray crystallography and computational modeling that have illuminated binding modes distinct from classical sulfonamide interactions. By synthesizing the latest findings, this review aims to guide future efforts in the rational design of selective and efficacious non-sulfonamide CA inhibitors for clinical application.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129646","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":"Medicinal Chemistry, SAR, and Molecular Insights Into 2,4-Thiazolidinediones as Antidiabetic Agents (2020–2025)","authors":"Neeru Malik,&nbsp;Rajesh Kumar Singh","doi":"10.1002/ardp.70102","DOIUrl":"https://doi.org/10.1002/ardp.70102","url":null,"abstract":"<div>\u0000 \u0000 <p>The thiazolidinedione (TZD) scaffold has long been recognized for its pharmacological versatility, particularly in the treatment of metabolic and inflammatory disorders. Among its derivatives, 2,4-thiazolidinediones (2,4-TZDs) have emerged as a prominent class of antidiabetic agents with diverse molecular targets. While their role as peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists is well established, recent studies have revealed additional therapeutic mechanisms, including inhibition of protein tyrosine phosphatase 1B (PTP-1B), α-amylase, α-glucosidase, and aldose reductase—each contributing to improved glucose regulation and diabetes management. Moreover, the rise of dual and multitarget inhibitors highlights the evolving therapeutic potential of 2,4-TZDs beyond conventional pathways. This review presents a comprehensive analysis of recent developments (2020–2025) in the medicinal chemistry, structure–activity relationships (SARs), and antidiabetic mechanisms of 2,4-TZDs. Key structural modifications and their influence on biological activity are critically evaluated, alongside updates on recent patent disclosures and ongoing clinical trials. By integrating medicinal chemistry insights with pharmacological data, this review aims to support the rational design of next-generation 2,4-TZD-based antidiabetic therapeutics.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111337","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}