Archiv der Pharmazie最新文献_第2页

The Current Landscape of 1,2,3-triazole Hybrids With Anticancer Therapeutic Potential: Part II 具有抗癌治疗潜力的1,2,3-三唑化合物的现状：第二部分

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-01 DOI: 10.1002/ardp.202500031

Zhi Xu, Junna Liu

引用次数: 0

Exploration of Aromatic Hydrazides as Inhibitors of Human Carbonic Anhydrases 芳香酰肼作为人碳酸酐酶抑制剂的研究

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-01 DOI: 10.1002/ardp.202400963

German Benito Menendez, Simone Giovannuzzi, Alessandro Bonardi, Alessio Nocentini, Paola Gratteri, Claudiu T. Supuran

{"title":"Exploration of Aromatic Hydrazides as Inhibitors of Human Carbonic Anhydrases","authors":"German Benito Menendez, Simone Giovannuzzi, Alessandro Bonardi, Alessio Nocentini, Paola Gratteri, Claudiu T. Supuran","doi":"10.1002/ardp.202400963","DOIUrl":"https://doi.org/10.1002/ardp.202400963","url":null,"abstract":"A large set of hydrazide-based derivatives were explored as inhibitors of the human (h) carbonic anhydrase (CA) isoforms I, II, IV, IX, and XII. A wide series of compounds were synthesized and then assessed for their CA inhibitory activity using a CO2 hydrase stopped-flow assay. Generally, these inhibitors demonstrated micromolar activity against the evaluated hCAs. Specifically, some derivatives bearing a ureido-linker exhibited the highest inhibitory potency, showing inhibition constants (KIs) in the low-micromolar range against hCAs IV, XI, and XII. Moreover, two of them were detected as submicromolar inhibitors of isoform IV (KIs: 0.8–0.96 µM). Molecular modeling was carried out to investigate the binding mode of the most selective and potent compounds and reinforce the experimental results. The latter suggests that hydrazide compounds act as zinc binders, being bidentate ligands, and can be developed as an alternative to classic CA inhibitors.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202400963","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143740938","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

Trimetazidine mitigates methotrexate-induced liver damage: Insights From biochemical, histological, and in silico analyses 曲美他嗪减轻甲氨蝶呤引起的肝损伤：从生化，组织学和计算机分析的见解

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-01 DOI: 10.1002/ardp.202400726

Maha R. A. Abdollah, Mohamed H. Aly, Maha E. Wally, Nada K. Sedky, Ahmed H. Saadawy, Eman Badr, Mai F. Tolba

{"title":"Trimetazidine mitigates methotrexate-induced liver damage: Insights From biochemical, histological, and in silico analyses","authors":"Maha R. A. Abdollah, Mohamed H. Aly, Maha E. Wally, Nada K. Sedky, Ahmed H. Saadawy, Eman Badr, Mai F. Tolba","doi":"10.1002/ardp.202400726","DOIUrl":"https://doi.org/10.1002/ardp.202400726","url":null,"abstract":"This study aimed at generating preliminary evidence for the potential utility of repurposing the clinically approved anti-ischemic drug trimetazidine (TMZ) against methotrexate (MTX)-induced hepatotoxicity. In this study, rats received MTX (30 mg/kg) with or without TMZ pretreatment (20 mg/kg). MTX caused a 2.7–3.6-fold increase in serum transaminases, while TMZ pretreatment caused a 37%–40% reduction. Regarding oxidative markers, MTX significantly suppressed the antioxidant glutathione (GSH) levels by 37% and elevated malondialdehyde (MDA) levels by 29%, while TMZ boosted GSH levels by 40% and reduced MDA levels by 20%. Next, we assessed nuclear factor kappa B (NF-κB) (p-65), nuclear factor erythroid 2-related factor 2 (Nrf2) and hemoxygenase-1 (HO-1) to find that MTX significantly elevated the levels of the proinflammatory nuclear factor kappa B (NF-κB) (p65) by 2.4-fold, while TMZ pretreatment reduced its levels by 48%. Conversely, MTX decreased the levels of Nrf2, HO-1, and adenosine triphosphate (ATP) by 55%–71%, while TMZ led to a threefold increase in their levels. Regarding apoptosis, MTX caused a five to sixfold elevation in B-cell lymphoma 2 associated X (Bax)/B-cell lymphoma 2 (BCL2) ratio and caspase-3, while TMZ pretreatment caused a threefold reduction in their levels. An in silico analysis of TMZ protein target-prediction revealed statistically enriched pathways related to oxidative stress, inflammation, and apoptosis. In conclusion, pretreatment with TMZ successfully ameliorated MTX-induced alterations in serum aminotransferases, liver histology, oxidative stress, and apoptosis. Pathway enrichment analysis (PEA) showed that TMZ is involved in multiple signaling and immune-related pathways that might be, at least partly, implicated in its cytoprotective effects.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143740941","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 potent N-hydroxycinnamamide-based histone deacetylase inhibitors suppress proliferation and trigger apoptosis in THP-1 leukaemia cells 新的有效的n -羟基肉桂酰胺基组蛋白去乙酰化酶抑制剂抑制THP-1白血病细胞的增殖并引发细胞凋亡

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-01 DOI: 10.1002/ardp.202400889

Magdalena Onuscakova, Tereza Kauerova, Eva Fialova, Hana Pizova, Vladimir Garaj, Miroslav Kemka, Vladimir Frecer, Peter Kollar, Pavel Bobal

{"title":"New potent N-hydroxycinnamamide-based histone deacetylase inhibitors suppress proliferation and trigger apoptosis in THP-1 leukaemia cells","authors":"Magdalena Onuscakova, Tereza Kauerova, Eva Fialova, Hana Pizova, Vladimir Garaj, Miroslav Kemka, Vladimir Frecer, Peter Kollar, Pavel Bobal","doi":"10.1002/ardp.202400889","DOIUrl":"https://doi.org/10.1002/ardp.202400889","url":null,"abstract":"A new group of potent histone deacetylase inhibitors (HDACis) capable of inhibiting cell growth and affecting cell-cycle progression in Tohoku Hospital Pediatrics-1 (THP-1) monocytic leukaemia cells was synthesized. The inhibitors belong to a series of hydroxamic acid derivatives. We designed and synthesized a series of 22 N-hydroxycinnamamide derivatives, out of which 20 are new compounds. These compounds contain various substituted anilides as the surface recognition moiety (SRM), a p-hydroxycinnamate linker, and hydroxamic acids as the zinc-binding group (ZBG). The whole series of synthesized hydroxamic acids inhibited THP-1 cell proliferation. Compounds 7d and 7p, which belong to the category of derivatives with the most potent antiproliferative properties, exert a similar effect on cell-cycle progression as vorinostat and induce apoptosis in THP-1 cells. Furthermore, compounds 7d and 7p were demonstrated to inhibit HDAC class I and II in THP-1 cells with comparable potency to vorinostat and increase acetylation of histones H2a, H2b, H3, and H4. Molecular modelling was used to predict the probable binding mode of the studied HDACis in class I and II histone deacetylases in terms of Zn2+ ion chelation by the hydroxamate group.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202400889","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143740936","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

Enhancing Polyacrylonitrile Nanofibers Antiviral Activity Using Greenly Synthesized Silver Nanoparticles 绿色合成纳米银增强聚丙烯腈纳米纤维抗病毒活性

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-01 DOI: 10.1002/ardp.202400943

Merna H. Emam, Reham S. Elezaby, Shady A. Swidan, Samah A. Loutfy, Rania M. Hathout

{"title":"Enhancing Polyacrylonitrile Nanofibers Antiviral Activity Using Greenly Synthesized Silver Nanoparticles","authors":"Merna H. Emam, Reham S. Elezaby, Shady A. Swidan, Samah A. Loutfy, Rania M. Hathout","doi":"10.1002/ardp.202400943","DOIUrl":"https://doi.org/10.1002/ardp.202400943","url":null,"abstract":"<div>\u0000 \u0000 Developing efficient antiviral protectives is a new approach against respiratory emerging viruses. This study aims to synthesize silver nanoparticles (Ag NPs) via a green technique using crocin to provide a virucidal effect and to enhance the protection of polyacrylonitrile (PAN) nanofibrous face masks or respirators against viruses. The influence of formulation and process variables on the particle size (PS) of Ag NPs was studied using d-optimal response surface design. The selected NPs were loaded into PAN nanofibers (NFs). MTT colorimetric assay was performed to determine the safety of the prepared NPs and NFs on Vero cells. Further, an immunofluorescent assay was performed to determine the composite's ability to inhibit the ACE2-SARS-CoV-2 spike protein interaction and prevent viral infection. The selected NPs possessed a small PS of 23.21 ± 0.86 nm, a PDI of 0.23 ± 0.019, and a ZP of –21.8 ± 1.82 mV. The optimum NF composite was fabricated with a PAN concentration of 8% w/v loaded with 0.25% w/w Ag NPs, with a feeding rate of 0.7 mL/h and an applied voltage of 23.5 kV. The resultant NFs displayed an acceptable morphology and a mean diameter of 378.88 ± 91.12 nm. In vitro cytotoxicity studies on Vero cells revealed the biocompatibility of crocin and Ag NPs. Moreover, Ag-PAN NFs were proven biologically safe. The immunofluorescent assay showed that Ag-PAN NFs demonstrated the least IC50 value of 10.99 µg/mL, indicating their potent effect on inhibiting SARS-CoV-2 infection. Ag-PAN NFs are a promising safe antiviral composite that has the potential to be used in face masks.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741049","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

Exosomal lncRNAs in the Tumor Angiogenesis: As Therapeutic Targets in Cancer Treatment 肿瘤血管生成中的外泌体lncRNAs：作为肿瘤治疗的治疗靶点

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-01 DOI: 10.1002/ardp.202400940

Chou-Yi Hsu, Farag M. A. Altalbawy, Enwa Felix Oghenemaro, Subasini Uthirapathy, Muktesh Chandra, Deepak Nathiya, Parjinder Kaur, M. Ravi Kumar, Abed J. Kadhim, Muthena Kariem

{"title":"Exosomal lncRNAs in the Tumor Angiogenesis: As Therapeutic Targets in Cancer Treatment","authors":"Chou-Yi Hsu, Farag M. A. Altalbawy, Enwa Felix Oghenemaro, Subasini Uthirapathy, Muktesh Chandra, Deepak Nathiya, Parjinder Kaur, M. Ravi Kumar, Abed J. Kadhim, Muthena Kariem","doi":"10.1002/ardp.202400940","DOIUrl":"https://doi.org/10.1002/ardp.202400940","url":null,"abstract":"Exosomes, as mediators of intercellular communication, can be released from different types of cells and regulate the function of the target cell by transferring cargo, such as proteins, DNA, and RNA. Recent investigations have revealed a preponderance of long noncoding RNAs (lncRNAs), a subclass of noncoding RNAs, within exosomes, where they exhibit notable stability and are implicated in the development and progression of neoplastic processes, such as tumor angiogenesis. Angiogenesis, as a hallmark of cancer, provides diffusible nutrients and oxygen to the distant cells and guarantees tumorigenesis and metastasis. Exosomal lncRNAs, including MALAT1, OIP5-AS1, PART1, SNHG family, FAM225A, ATB, RAMP2-AS1, UCA1, TRPM2-AS, FGD5-AS1, and LINC0016, could modulate tumor angiogenesis by activating signaling cascades and mediators within the target cells, such as microRNAs (miRNAs). Regulation of tumor angiogenesis through modulation of exosomal lncRNAs could be a reliable strategy for cancer therapy. In this review, we discuss the characteristics and biogenesis of exosomes and lncRNAs and how exosomal lncRNAs are involved in various processes of tumorigenesis. Our primary focus is on exosomal lncRNAs, their impact on tumor angiogenesis, and their potential as novel diagnostic markers and therapeutic targets for various cancers.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143740939","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

Issue Information: Arch Pharm (4/2025) 发行资讯：大药房（4/2025）

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-01 DOI: 10.1002/ardp.2570004

引用次数: 0

Implication of Central β2 Adrenergic Receptor for the Development of Novel Drugs Against Alzheimer's Disease 中枢β2肾上腺素能受体在阿尔茨海默病新药开发中的意义

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-04-01 DOI: 10.1002/ardp.202400750

Alice Wang, Marc Since, Patrick Dallemagne, Christophe Rochais

引用次数: 0

A decade of research effort in synthesis, biological activity assessments, and mechanistic investigations of sulfamethazine-incorporating molecules 在合成、生物活性评估和结合磺胺乙胺分子的机理研究方面的十年努力

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-24 DOI: 10.1002/ardp.202500033

Hamada S. Abulkhair, Khaled El-Adl

{"title":"A decade of research effort in synthesis, biological activity assessments, and mechanistic investigations of sulfamethazine-incorporating molecules","authors":"Hamada S. Abulkhair, Khaled El-Adl","doi":"10.1002/ardp.202500033","DOIUrl":"https://doi.org/10.1002/ardp.202500033","url":null,"abstract":"Because of its importance in medicinal chemistry, scientific researchers have been interested in incorporating sulfamethazine in developing biologically active candidates. To achieve this, several synthetic approaches have been adopted. The adopted approaches included condensation with electrophilic reactants, coupling with nucleophilic aromatics and active methylene compounds, Knoevenagel condensation, Doebner Miller reaction, microwave-assisted click cycloaddition, green reaction routes, and multicomponent reaction. Linking this molecular scaffold to a variety of heterocycles in the last 10 years furnished a set of potential anti-inflammatory, antiviral, anticancer, antiparkinsonian, neuroprotective, and antidiabetic candidates targeting H5N1 NA, epidermal growth factor receptor, acetylcholinesterase (AChE), butylcholinesterase (BChE), human carbonic anhydrase (hCA), α-amylase, and α-glucosidase. This review reports all the adopted synthetic approaches, the biological activities studied, structure-activity relationship analyses, and the mechanistic investigations of the reported organic sulfamethazine-incorporating molecules throughout 2015–2024, based on information retrieved from three search engines: Scopus, PubMed, and Google Scholar.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690157","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

Dual inhibition of carbonic anhydrases VA and VII by silychristin and isosilybin A from Silybum marianum: A potential antiobesity strategy 水飞蓟中的水飞蓟素和异水飞蓟素A对VA和VII碳酸酐酶的双重抑制：一种潜在的抗肥胖策略

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-24 DOI: 10.1002/ardp.202400966

Emanuele Liborio Citriniti, Roberta Rocca, Giosuè Costa, Gioele Renzi, Fabrizio Carta, Claudiu T. Supuran, Stefano Alcaro, Francesco Ortuso

{"title":"Dual inhibition of carbonic anhydrases VA and VII by silychristin and isosilybin A from Silybum marianum: A potential antiobesity strategy","authors":"Emanuele Liborio Citriniti, Roberta Rocca, Giosuè Costa, Gioele Renzi, Fabrizio Carta, Claudiu T. Supuran, Stefano Alcaro, Francesco Ortuso","doi":"10.1002/ardp.202400966","DOIUrl":"https://doi.org/10.1002/ardp.202400966","url":null,"abstract":"Obesity is a global health crisis linked to chronic diseases like cardiovascular disease and type 2 diabetes. Its prevalence, even in low-income countries, highlights the failure of traditional interventions. Safer pharmacological treatments are urgently needed, as many existing antiobesity drugs have been withdrawn due to severe side effects, leaving a critical therapeutic gap. A promising target in this context is human carbonic anhydrase V (hCA V), a mitochondrial enzyme that plays a key role in glucose homeostasis. Inhibiting hCA V has been shown to reduce lipogenesis and improve metabolic conditions. Natural plant extracts, such as silymarin from milk thistle, have demonstrated potential in managing obesity-related metabolic syndromes by lowering triglycerides, reducing cholesterol levels, and improving liver function. Our computational studies have identified active compounds in silymarin that effectively inhibit hCA V, shedding light on a potential mechanism for its antiobesity effects. Building on these findings, our research further reveals that these compounds also inhibit carbonic anhydrase VII (hCA VII), enhancing their therapeutic potential. This dual inhibitory action addresses both metabolic dysregulation and oxidative stress. Notably, the antioxidant properties of hCA VII provide additional protection against obesity-related complications by mitigating oxidative stress, a key contributor to the development of metabolic syndrome.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202400966","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689850","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