Archiv der Pharmazie最新文献

{"title":"Novel Kojic Acid-Thiadiazole-Urea Hybrids: Potent Tyrosinase Inhibitors With Enhanced Anti-Melanogenic Activity","authors":"Ayyub Mojaddami,&nbsp;Mojtaba Hamzi,&nbsp;Mehdi Khoshneviszadeh,&nbsp;Maryam Kabiri,&nbsp;Mahshid Attarroshan,&nbsp;Alireza Foroumadi,&nbsp;Mahsa Toolabi","doi":"10.1002/ardp.70147","DOIUrl":"https://doi.org/10.1002/ardp.70147","url":null,"abstract":"<div>\u0000 \u0000 <p>A new class of kojic acid–derived tyrosinase inhibitors was rationally designed through the incorporation of a thiadiazole-urea framework. Accordingly, a series of 1-(aryl)-3-(5-{[(5-hydroxy-4-oxo-4<i>H</i>-pyran-2-yl)methyl]thio}-1,3,4-thiadiazol-2-yl)urea derivatives was synthesized starting from thiosemicarbazide. Through this approach, 13 new compounds were prepared with good yields via a straightforward procedure. The strategy involved substituting the hydroxymethyl group with a thiadiazol-urea pharmacophore, leading to the discovery of compounds that exhibited significantly enhanced inhibitory activity (IC₅₀ range: 0.02–0.96 µM) compared to kojic acid (IC₅₀ = 64.32 µM) against tyrosinase. Further kinetic, antioxidant, and docking studies, along with melanin content assays, were conducted to elucidate the mechanism of action for the most active compounds.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619350","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":"Reevaluating 1,3-Thiazolidinone Reports: Deciphering the Authentic 1,3-Thiazolidinone Frameworks via Synthetic and Spectroscopic Insights","authors":"Roghayeh Hosseininia,&nbsp;Farough Nasiri","doi":"10.1002/ardp.70157","DOIUrl":"https://doi.org/10.1002/ardp.70157","url":null,"abstract":"<div>\u0000 \u0000 <p>Accurate structural determination of heterocyclic scaffolds is essential for medicinal chemistry and drug discovery. In this study, products obtained from three-component reactions of aryl isothiocyanates, dialkyl acetylenedicarboxylates, and hydrazine hydrate, as well as four-component reactions incorporating aldehydes, were carefully re-examined. Previous studies had described these compounds as thiazine derivatives; however, our comprehensive synthetic and spectroscopic investigations demonstrate that they actually correspond to thiazolidinone frameworks. Key evidence was provided by gradient-selected heteronuclear multiple bond correlation (HMBC) and gated ¹³C NMR spectroscopy, which enabled the determination of regioselectivity and stereochemical features. Comparative analysis with reported X-ray crystallographic data further supported our revised assignments. These results resolve inconsistencies in earlier reports and highlight the critical importance of rigorous characterization in multicomponent heterocyclic synthesis. The findings establish a reliable framework for the identification of related heterocycles, thereby offering valuable guidance for future applications in drug-oriented synthesis and the design of bioactive molecules.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626413","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":"Mechanistic Insights into the Anticancer Potential of Echinacoside: Therapeutic Applications and Future Directions","authors":"Anju Sheokand,&nbsp;Dolly Koli,&nbsp;Karan Wadhwa,&nbsp;Gulshan Sharma,&nbsp;Rakesh Pahwa,&nbsp;Hardeep Singh Tuli","doi":"10.1002/ardp.70153","DOIUrl":"https://doi.org/10.1002/ardp.70153","url":null,"abstract":"<div>\u0000 \u0000 <p>Echinacoside, a naturally occurring phenylethanoid glycoside, primarily derived from medicinal plants such as <i>Cistanche tubulosa</i> and <i>Echinacea angustifolia</i>, has long been valued in traditional medicine for its diverse pharmacological activities, including antidiabetic, anti-inflammatory, antifatigue, anti-allergic, antiaging, wound healing, and aphrodisiac effects. Recent research has steadily highlighted echinacoside's promising role as a multi-targeted oncotherapeutic agent due to its potent anticancer properties. Its antineoplastic efficacy is mediated through multiple mechanisms, including induction of apoptosis, inhibition of metastasis and angiogenesis, and modulation of key oncogenic signaling pathways such as PI3K/Akt/mTOR and MAPK/ERK. Additionally, echinacoside has significant synergistic potential with traditional chemotherapeutics, enhancing cytotoxicity while mitigating systemic toxicity and overcoming drug resistance. Despite compelling evidence for its multi-targeted anticancer mechanisms, its clinical translation is restricted by various pharmacokinetic challenges, including limited absorption and fast metabolic clearance. Although few reviews have addressed the general pharmacological activities of echinacoside, this article provides a novel and forward-looking perspective by critically bridging the gap between its multi-targeted anticancer mechanisms and its translational potential. This manuscript also comprehensively integrates the latest preclinical findings, particularly highlighting emerging nanotechnological and synergistic strategies designed to overcome its bioavailability and stability barrier, thereby uniquely outlining a strategic roadmap for future research to facilitate the clinical application of echinacoside into precision oncology.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626466","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 of Promising Biguanide Derivatives Bearing Urea/Thiourea as Type II Antidiabetic Agents","authors":"Wahid M. Basyouni,&nbsp;Samir Y. Abbas,&nbsp;Eman A. Younis,&nbsp;Hanan F. Aly","doi":"10.1002/ardp.70150","DOIUrl":"https://doi.org/10.1002/ardp.70150","url":null,"abstract":"<div>\u0000 \u0000 <p>Novel biguanide hydrochloride salts were synthesized through the reaction of <i>N</i>-substituted-semi(thiosemi)carbazides with cyanoguanidine in an acidic medium. Antidiabetic properties of the synthesized biguanides were evaluated for their antidiabetic properties. All biguanide compounds showed promising effects, which revealed a significant decrease in the elevated glucose in comparison with metformin on oral treatment of hyperglycemic rats with the synthesized biguanide derivatives. The monosubstituted thiourea showed an improvement by about 1.48-fold of metformin. The effect of the synthesized biguanides on liver function enzyme activities, lipid profiles, and renal functions was investigated and discussed as compared with normal control rats; some urea derivatives showed improvement results that were nearly equal to those of metformin. Regarding lipid profile, the <i>N</i>-phenylurea moiety showed improved results higher than metformin. Regarding the effect on kidney function markers, some urea derivatives showed results that were higher than those of metformin. Also, antioxidant biomarkers and inflammatory markers were detected in diabetic rats and discussed; the results of all tested derivatives were equal to twofold of the results of metformin. Moreover, the histopathological examination of hepatic, kidney, and pancreatic tissues reveals that all of the tested compounds showed significant, promising activity.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619275","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":"Bruceantin and Brusatol: Molecular Insights and Therapeutic Promise of Quassinoids in Cancer Drug Discovery","authors":"Shumaila Ijaz,&nbsp;Javed Iqbal,&nbsp;Banzeer Ahsan Abbasi,&nbsp;Farishta Zarshan,&nbsp;Tabassum Yaseen,&nbsp;Zakir Ullah,&nbsp;Siraj Uddin,&nbsp;Sobia Kanwal,&nbsp;Tariq Mahmood,&nbsp;William N. Setzer,&nbsp;Javad Sharifi-Rad,&nbsp;Daniela Calina","doi":"10.1002/ardp.70142","DOIUrl":"https://doi.org/10.1002/ardp.70142","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer remains a leading cause of mortality worldwide, with treatment resistance posing a major obstacle to effective therapies. Natural compounds, including quassinoids such as bruceantin and brusatol, derived from <i>Brucea javanica</i> (L.) Merr., have demonstrated potential as novel cancer chemopreventive agents. Bruceantin exhibits cytotoxic effects against diverse cancer cell lines, including leukemia, lymphoma, and myeloma, primarily through inhibition of protein synthesis and induction of apoptosis via caspase and mitochondrial pathways. Similarly, brusatol has shown broad-spectrum anticancer activities by modulating cellular processes such as apoptosis, cell-cycle arrest, autophagy, and attenuation of epithelial–mesenchymal transition. Mechanistically, it targets key oncogenic signaling pathways, including PI3K/AKT/mTOR and Keap1/NRF2, and enhances chemosensitivity and radiosensitivity. This review evaluates preclinical findings on the pharmacological properties, mechanisms of action, and anticancer efficacy of bruceantin and brusatol. Their structural modifications, safety profiles, and challenges such as poor bioavailability and systemic toxicity are also explored. Advances in semi-synthetic derivatives and drug delivery systems are discussed as strategies to enhance therapeutic potential. Comprehensive insights are provided into the molecular and cellular mechanisms underlying their anticancer effects, supported by in vitro and in vivo evidence. Collectively, these findings highlight the promise of bruceantin and brusatol as therapeutic agents and underscore the need for further translational research to optimize their clinical utility. These quassinoids represent a compelling avenue for the development of targeted and adjunctive cancer therapies, potentially overcoming limitations of conventional treatments.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619266","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":"Indole Hybrids With Therapeutic Potential Against Drug-Resistant Cancers: An Update (2021–2025)","authors":"Xiaoyu Li,&nbsp;Feng Wang,&nbsp;Lin Xie","doi":"10.1002/ardp.70156","DOIUrl":"10.1002/ardp.70156","url":null,"abstract":"<div>\u0000 \u0000 <p>Drug-resistant cancer is a major obstacle to effective treatment, causing poor clinical outcomes, financial pressure, and healthcare burdens, highlighting the urgent need for new chemotherapeutics. Indole derivatives are valuable anticancer scaffolds with multitargeted effects. Indole hybrids, in particular, exert multitargeted actions that address drug resistance mechanisms, offering unique advantages for overcoming resistant cancers. The present manuscript aims to summarize the current landscape of indole hybrids, with therapeutic potential against drug-resistant cancers, covering literature published since 2021. Additionally, the structure–activity relationships and mechanisms of action are addressed to inform the further rational design of novel candidates.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601392","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":"Microwave-Enhanced Synthesis of 2-Styrylquinoline-4-Carboxamides With Promising Anti-Lymphoma Activity","authors":"Ignazio Sardo,&nbsp;Lorenzo Manfreda,&nbsp;Giulia Maria Titone,&nbsp;Marilia Barreca,&nbsp;Roberta Bivacqua,&nbsp;Virginia Spanò,&nbsp;Sara Amata,&nbsp;Arianna Zanolli,&nbsp;Roberta Bortolozzi,&nbsp;Maria Valeria Raimondi,&nbsp;Giampietro Viola,&nbsp;Paola Barraja,&nbsp;Alessandra Montalbano","doi":"10.1002/ardp.70148","DOIUrl":"10.1002/ardp.70148","url":null,"abstract":"<p>Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, characterized by significant clinical and molecular heterogeneity. Here, we report the design and synthesis of a novel series of 2-styrylquinoline-4-carboxamides via an efficient microwave-assisted organic synthesis (MAOS) approach. This strategy enabled the rapid and high-yielding isolation of derivatives <b>4a–z</b> and <b>4aa–ah</b> in three steps from commercially available isatin. Among the 34 compounds synthesized, 24 showed antiproliferative activity in vitro, with compound <b>4i</b> displaying sub-micromolar IC₅₀ values across multiple lymphoma cell lines, including SU-DHL-8 and TOLEDO. Mechanism of action studies demonstrated that <b>4i</b> was able to induce G₂/M cell-cycle arrest and DNA synthesis suppression, coupled with mitochondrial membrane depolarization and reactive oxygen species (ROS) accumulation, suggesting activation of the intrinsic apoptotic pathway. Importantly, active derivatives were nontoxic to healthy peripheral blood mononuclear cells (PBMCs), indicating a favorable therapeutic window. These results validate the quinoline scaffold as a promising chemotype, highlighting the utility of MAOS for the sustainable synthesis of bioactive heterocycles.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595465","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":"Identification and Validation of Novel Lactylation-Related Gene Signature in Dilated Cardiomyopathy","authors":"Jia Liu,&nbsp;Chong Liu,&nbsp;Jingjia Yu,&nbsp;Kai Xu","doi":"10.1002/ardp.70154","DOIUrl":"10.1002/ardp.70154","url":null,"abstract":"<div>\u0000 \u0000 <p>Dilated cardiomyopathy (DCM) is a progressive myocardial disorder with limited therapeutic options. Recent studies suggest that metabolic reprogramming, including lactate accumulation and protein lactylation, contributes to heart failure pathogenesis, but their roles in DCM remain poorly defined. We analyzed the global burden of cardiomyopathy and myocarditis using GBD data and performed transcriptomic profiling using GSE120895 and GSE5406 datasets. Weighted gene co-expression network analysis (WGCNA), differential gene expression, and known lactylation-related genes (LRGs) were integrated to identify key targets. LASSO regression was applied to construct a diagnostic model. Validation was conducted in an Lmna^E82K transgenic mouse model using qRT-PCR, Western blot analysis, immunofluorescence, and biochemical assays. Global analysis showed the rising age-standardized prevalence of cardiomyopathy and myocarditis by 2021. Bioinformatics revealed 1988 DEGs in DCM, 11 of which overlapped with LRGs and WGCNA modules. LASSO modeling identified <i>DDX39A</i>, <i>SPR</i>, and <i>HNRNPC</i> as core diagnostic biomarkers. In vivo validation confirmed upregulation of these genes in Lmna^E82K mice. Elevated lactate and protein lactylation levels were detected, alongside increased NEFA, MDA, and oxidative stress markers, implicating lactylation in metabolic dysfunction. We identify <i>DDX39A</i>, <i>SPR</i>, and <i>HNRNPC</i> as novel lactylation-associated biomarkers of DCM and reveal a pathophysiological link between lactate-driven protein lactylation, oxidative stress, and cardiac dysfunction. These findings offer new molecular targets for DCM diagnosis and intervention.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595423","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":"Erratum: Investigating the Hepatoprotective Properties of Entresto in Hepatic Ischemia-Reperfusion Injury in Rats: The Implication of TLR4/MYD88/NF-KB p-65 and PPAR-γ/Ho-1/Nrf2 Pathways","authors":"","doi":"10.1002/ardp.70160","DOIUrl":"10.1002/ardp.70160","url":null,"abstract":"<p>by Alaa Abouelhamd, Dalia H. Abu-Baih, Sara Mohamed Naguib Abdel-Hafez, Moustafa Fathy</p><p>The affiliations of Moustafa Fathy, one of the corresponding authors of the article published as <i>Arch. Pharm</i>. 2025;358:e70138, https://doi.org/10.1002/ardp.70138, were not correctly presented. The correct affiliations are:</p><p>Moustafa Fathy^4,5</p><p>⁴Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt</p><p>⁵Department of Biochemistry, Faculty of Pharmacy, Minia National University, New Minia, Egypt</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595497","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":"Investigation on LASSBio-1971 and LASSBio-1974 Cellular Cytotoxic Mechanism and Their Comparative DMPK Profile","authors":"Manoel Oliveira de Moraes Junior,&nbsp;Gisele Barbosa,&nbsp;Caroline Marques Xavier da Costa,&nbsp;Raysa Magali Pillpe-Meza,&nbsp;Wesley Leandro de Gouveia,&nbsp;Daniel Nascimento do Amaral,&nbsp;Luis Gabriel Valdivieso Gelves,&nbsp;Stefan Laufer,&nbsp;Lídia Moreira Lima","doi":"10.1002/ardp.70151","DOIUrl":"10.1002/ardp.70151","url":null,"abstract":"<p>Due to the arising of clinically relevant resistant EGFR-related phenotype through innovative mechanisms, mainly EGFR_L858R/T790M, the emergence of novel molecules with dual or multi-target affinity has presented a promising alternative to overcoming these resistance mechanisms. This study aimed to evaluate synthetic acrylamide quinoxaline derivatives against NSCLC cell lines with different overexpressed EGFR mutations and compare their DMPK profile. The biological activity of LASSBio-1971 and LASSBio-1974 was assessed through cytotoxicity (MTT and Sulforhodamine B assays), apoptosis induction, EGFR inhibition, cell cycle analysis (flow cytometry), immunofluorescence microscopy, cell membrane permeability (PAMPA assay), and metabolic stability in rat liver microsomes. LASSBio-1971 exhibited promising EGFR inhibition with favorable in vitro pharmacokinetic (PK) properties, including high gastrointestinal and blood–brain barrier permeability. LASSBio-1974 demonstrated nonselective mechanism inhibiting EGFR and mitotic machinery leading to apoptosis and cell cycle arrest at different phases. LASSBio-1971 and LASSBio-1974 emerge as EGFR inhibitors with equipotent cytotoxic effects on human NSCLC lines and different in PK profile. Further studies should be conducted with LASSBio-1974 to prove and understand its antimicrotubule action.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562029","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}