Archiv der Pharmazie最新文献_第5页

A simplified optimization approach for sample preparation workflow in LC-MS-based quantitative proteomic analysis: Biological samples to peptides

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-04 DOI: 10.1002/ardp.202400911

Surendra Fartade, Tarang Jadav, Niraj Rajput, Pinaki Sengupta

{"title":"A simplified optimization approach for sample preparation workflow in LC-MS-based quantitative proteomic analysis: Biological samples to peptides","authors":"Surendra Fartade, Tarang Jadav, Niraj Rajput, Pinaki Sengupta","doi":"10.1002/ardp.202400911","DOIUrl":"https://doi.org/10.1002/ardp.202400911","url":null,"abstract":"Quantitative proteomics, an integral subfield within proteomics, is pivotal for elucidating complex biological processes. By integrating with other omics data, quantitative proteomics facilitates system-level analysis and significantly advances our understanding of cellular networks and disease mechanisms. The ongoing advancements in quantitative proteomics technology significantly boost its importance by improving analytical accuracy. This review focuses on quantitative proteomics employing liquid chromatography-mass spectrometry (LC-MS), a cornerstone technique renowned for its sensitivity, selectivity, accuracy, and throughput. The efficacy of LC-MS proteomics is heavily reliant on sample preparation, which encompasses protein extraction, total protein estimation, reduction, alkylation, digestion, and cleanup. For the very first time, this article provides a detailed examination of sample preparation methods offering insights and guidelines that researchers can utilize to refine their experimental protocols which were not critically evaluated before. By optimizing sample preparation workflows, researchers can enhance the robustness and reproducibility of their proteomic studies. By understanding the complexities of sample preparation in quantitative proteomics, researchers can optimize their experimental workflow to improve the robustness and reproducibility of their results. This review provides a comprehensive overview of sample preparation strategies in quantitative proteomics using LC-MS, discussing the underlying principles and key considerations for each step. By delving into the complexities of sample preparation, this article aims to aid researchers in optimizing their workflows to achieve robust and reproducible results, which ultimately drive innovations and breakthroughs in biomedical research and healthcare.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554669","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

Advances in the activity of resveratrol and its derivatives in cardiovascular diseases

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-02-16 DOI: 10.1002/ardp.202400865

Yaling Peng, Xing Zheng, Si Zhang, Zhongqin Luo, Li Song, Hongfei Chen, Xu Yao

引用次数: 0

Issue Information: Arch Pharm (2/2025) 发行信息：Arch Pharm (2/2025)

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-02-13 DOI: 10.1002/ardp.2570002

引用次数: 0

Antiviral metabolites from Passiflora edulis: An in vitro, phytochemical, and computational studies 西番莲中的抗病毒代谢物：体外、植物化学和计算研究

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-02-13 DOI: 10.1002/ardp.202400853

Abeer H. Elmaidomy, Michelle Teutsch, Jochen Bodem, Ruqaiah I. Bedaiwi, Mubarak A. Alzubaidi, Hisham A. Abou-Zied, Usama Ramadan Abdelmohsen

{"title":"Antiviral metabolites from Passiflora edulis: An in vitro, phytochemical, and computational studies","authors":"Abeer H. Elmaidomy, Michelle Teutsch, Jochen Bodem, Ruqaiah I. Bedaiwi, Mubarak A. Alzubaidi, Hisham A. Abou-Zied, Usama Ramadan Abdelmohsen","doi":"10.1002/ardp.202400853","DOIUrl":"https://doi.org/10.1002/ardp.202400853","url":null,"abstract":"Yellow fever (YF) is a mosquito-borne virus with high mortality rates, affecting regions in South America and Africa. Despite the effectiveness of YF vaccines, increased global demand and reports of rare, severe side effects have spurred the search for safer therapeutic alternatives. Current treatments lack specific antiviral drugs approved for YF, underscoring the need for new, effective therapies. This study investigated the potential of Passiflora edulis f. edulis leaf and stem extracts as antiviral agents against the yellow fever virus (YFV). In vitro tests showed that the extracts significantly reduced YFV viral loads by twofold in Huh-7 cells and 1.5-fold in Vero-h-Slam cells at a concentration of 50 µg/mL, with a smaller reduction at 25 µg/mL and no cytotoxic effects on either cell line. Phytochemical analysis identified a new C-deoxyhexosyl flavone, luteolin-8-(1-C-β-boivinopyranosyl)-4′1-O-β-d-glucopyranoside, along with several known compounds. Protein–protein interaction (PPI) network analysis using the STRING database and Cytoscape software revealed key hub genes, including IFNA1, IL7R, CD19, IL2RA, and IFNG, crucial in antiviral defense. Molecular docking studies further evaluated how these compounds interact with the YFV NS2B-NS3 protease, essential for viral replication. Molecular dynamics (MD) simulations confirmed the stability of these interactions over a 120-nanosecond period, supporting the compounds’ antiviral potential. This study demonstrates the promise of Passiflora edulis metabolites as a foundation for developing novel YFV therapies by combining computational and experimental insights.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting the isoprenoid pathway in choleste biosynthesis: An approach to identify isoprenoid biosynthesis inhibitors 以胆固醇生物合成中的异戊二烯途径为目标：鉴定异戊二烯生物合成抑制剂的方法

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-02-13 DOI: 10.1002/ardp.202400807

Maximilian Liebl, Florian Olander, Christoph Müller

{"title":"Targeting the isoprenoid pathway in choleste biosynthesis: An approach to identify isoprenoid biosynthesis inhibitors","authors":"Maximilian Liebl, Florian Olander, Christoph Müller","doi":"10.1002/ardp.202400807","DOIUrl":"https://doi.org/10.1002/ardp.202400807","url":null,"abstract":"The development of novel cholesterol biosynthesis inhibitors is a task of major concern due to the diverse roles of cholesterol and its precursors in physiological processes. Therefore, appropriate screening assays are required, which can be used to identify and quantify specific inhibitors targeting the desired enzyme. Here, we developed a whole-cell screening assay based on a HL60 cell line, which can be used to characterize inhibitors interacting with enzymes of the isoprenoid part of cholesterol biosynthesis. Due to the change of the isoprenoid pattern under enzyme inhibition, an identification of the targeted enzyme is possible. With the described assay, we can distinguish between free and pyrophosphorylated isoprenoids after enzymatic cleavage in cellular and extracellular matrices. The approach was validated in line with the European Medicines Agency guideline on bioanalytical method validation. As proof of concept, literature-described inhibitors of the isoprenoid pathway were tested. We characterized the effect of 11 isoprenoid biosynthesis inhibitors, and we identified 6-fluoromevalonate as an isopentenyl pyrophosphate isomerase inhibitor, a biological activity that was previously unknown. Furthermore, isoprenoid patterns revealed that, independent of the analyzed matrix, the predominant form of the detected isoprenoids were dephosphorylated isoprenoids and only small amounts were present as pyrophosphates.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202400807","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396845","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

Natural products against tau hyperphosphorylation-induced aggregates: Potential therapies for Alzheimer's disease

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-01-30 DOI: 10.1002/ardp.202400721

Gustavo Basurto-Islas, Maximiliano Caye Diaz, Lizeth M. Zavala Ocampo, Melchor Martínez-Herrera, Perla Y. López-Camacho

{"title":"Natural products against tau hyperphosphorylation-induced aggregates: Potential therapies for Alzheimer's disease","authors":"Gustavo Basurto-Islas, Maximiliano Caye Diaz, Lizeth M. Zavala Ocampo, Melchor Martínez-Herrera, Perla Y. López-Camacho","doi":"10.1002/ardp.202400721","DOIUrl":"10.1002/ardp.202400721","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory impairments and is considered the most prevalent form of dementia. Among the contributing factors to AD lies the hyperphosphorylation of the microtubule-associated protein tau. Phosphorylated tau reduces its affinity for microtubules and triggers other posttranslational modifications that result in its aggregation and assembly into filaments. These structures progressively accumulate within neurons leading to neurodegeneration. While current AD medications often involve undesirable side effects, the exploration of natural products as a potential therapeutic alternative has gained considerable attention. Numerous compounds have shown potential capacity for reducing tau pathology through different mechanisms, such as inhibiting kinases to reduce tau hyperphosphorylation, enhancing phosphatase activity, and blocking fibril formation. Since tau hyperphosphorylation-induced aggregation is pivotal in AD onset, this review aims to elucidate the potential of natural products in modulating this crucial molecular mechanism.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062241","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

Synthesis and biological investigation of peptidomimetic SARS-CoV-2 main protease inhibitors bearing quinoline-based heterocycles at P3

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-01-28 DOI: 10.1002/ardp.202400812

Sara Rossi, Graziano Deidda, Lia Fiaschi, Roberta Ibba, Mariachiara Pieroni, Maria Dichiara, Gabriele Carullo, Stefania Butini, Anna Ramunno, Simone Brogi, Marco Lolicato, Cristina Arrigoni, Noemi Cabella, Laura Bavagnoli, Giovanni Maga, Ilenia Varasi, Camilla Biba, Ilaria Vicenti, Sandra Gemma, Emmanuele Crespan, Maurizio Zazzi, Giuseppe Campiani

{"title":"Synthesis and biological investigation of peptidomimetic SARS-CoV-2 main protease inhibitors bearing quinoline-based heterocycles at P3","authors":"Sara Rossi, Graziano Deidda, Lia Fiaschi, Roberta Ibba, Mariachiara Pieroni, Maria Dichiara, Gabriele Carullo, Stefania Butini, Anna Ramunno, Simone Brogi, Marco Lolicato, Cristina Arrigoni, Noemi Cabella, Laura Bavagnoli, Giovanni Maga, Ilenia Varasi, Camilla Biba, Ilaria Vicenti, Sandra Gemma, Emmanuele Crespan, Maurizio Zazzi, Giuseppe Campiani","doi":"10.1002/ardp.202400812","DOIUrl":"10.1002/ardp.202400812","url":null,"abstract":"In the last few years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the cause of a worldwide pandemic, highlighting the need for novel antiviral agents. The main protease (Mpro) of SARS-CoV-2 was immediately identified as a crucial enzyme for viral replication and has been validated as a drug target. Here, we present the design and synthesis of peptidomimetic Mpro covalent inhibitors characterized by quinoline-based P3 moieties. Structure–activity relationships (SARs) were also investigated at P1 and P2, as well as for different warheads. The binding modes of the designed inhibitors were assessed using X-ray crystallographic and molecular docking studies. The identified Mpro inhibitors were tested for their antiviral activities in cell-based assays, and the results were encouraging. The SAR studies presented here can contribute to the future design of improved inhibitors by addressing some of the current or prospective issues regarding Mpro inhibitors currently used in therapy.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051113","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

FDA-approved drugs featuring macrocycles or medium-sized rings

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-01-25 DOI: 10.1002/ardp.202400890

Youlong Du, Anas Semghouli, Qian Wang, Haibo Mei, Loránd Kiss, Daniel Baecker, Vadim A. Soloshonok, Jianlin Han

引用次数: 0

Synthesis of new dihydropyrimidine derivatives and investigation of their antimicrobial and DNA gyrase inhibitory activities 新型二氢嘧啶衍生物的合成及其抑菌和抑制DNA旋切酶活性的研究。

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-01-21 DOI: 10.1002/ardp.202400795

Asaf Evrim Evren, Demokrat Nuha, Sam Dawbaa, Uğur Kayış, Ülküye Dudu Gül, Leyla Yurttaş

{"title":"Synthesis of new dihydropyrimidine derivatives and investigation of their antimicrobial and DNA gyrase inhibitory activities","authors":"Asaf Evrim Evren, Demokrat Nuha, Sam Dawbaa, Uğur Kayış, Ülküye Dudu Gül, Leyla Yurttaş","doi":"10.1002/ardp.202400795","DOIUrl":"10.1002/ardp.202400795","url":null,"abstract":"Quinolone antibiotics are known for their antibacterial activity by inhibiting the enzyme DNA gyrase. Inspired by their mechanism, new compounds combining 1,4-dihydropyrimidine, a quinolone isostere, with pyridine/pyrimidine rings were synthesized. These derivatives showed antibacterial effects, likely through DNA gyrase inhibition, as supported by molecular docking and dynamics simulations. The synthesized compounds, 2-[(5-cyano-6-oxo-6-(pyridin-4-yl)-1,6-dihydropyrimidin-2-yl]-N-(benzothiazol-2-yl)-acetamide (5a–5g) and 2-[(5-cyano-6-oxo-6-(pyridin-4-yl)-1,6-dihydropyrimidin-2-yl)thio]-N-(thiazol-2-yl)acetamide (6a–6f), were evaluated for antibacterial activity. Compounds 5a, 6b, and 6c demonstrated significant bactericidal effects. Against Escherichia coli, compounds 6b and 6c exhibited minimum inhibitory concentration (MIC) values of 1.95 and 0.97 µg/mL, respectively, comparable to the standard drug. Compound 5a also showed strong activity against Escherichia faecalis. DNA gyrase inhibition studies confirmed that 5a, 6b, and 6c inhibit the enzyme, as no supercoiled DNA band was observed. These findings highlight the potential of these compounds as antibacterial agents. Future development could focus on optimizing these structures for enhanced activity, similar to quinolone antibiotics.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996784","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

Pyrimidine scaffold dual-target kinase inhibitors for cancer diseases: A review on design strategies, synthetic approaches, and structure–activity relationship (2018‒2023) 嘧啶支架双靶点激酶抑制剂治疗癌症：设计策略、合成方法和构效关系综述（2018-2023）。

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-01-19 DOI: 10.1002/ardp.202400163

Moeun Song, Ahmed Elkamhawy, Woojeong Noh, Ahmed Z. Abdelazem, Younggeun Park, Aneesh Sivaraman, Arailym Bertleuova, Dalia Atef, Kyeong Lee

{"title":"Pyrimidine scaffold dual-target kinase inhibitors for cancer diseases: A review on design strategies, synthetic approaches, and structure–activity relationship (2018‒2023)","authors":"Moeun Song, Ahmed Elkamhawy, Woojeong Noh, Ahmed Z. Abdelazem, Younggeun Park, Aneesh Sivaraman, Arailym Bertleuova, Dalia Atef, Kyeong Lee","doi":"10.1002/ardp.202400163","DOIUrl":"10.1002/ardp.202400163","url":null,"abstract":"Cancer, the second leading cause of death globally, causes a significant threat to life. Despite advancements in the treatment of cancer, persistent challenges include severe side effects and the emergence of acquired drug resistance. Additionally, many traditional chemotherapy drugs show restricted efficacy and high toxicity, primarily attributed to their lack of selectivity. Thus, the development of drugs targeting protein kinases has emerged as a noteworthy priority for addressing human cancers. Medicinal chemists have shown considerable interest in the development of dual drug candidates as a strategy to create medicines that are safer, more efficient, and cost-effective. Furthermore, the Food and Drug Administration (FDA) has approved several dual-target drugs for anticancer treatment, emphasizing their lower risks of drug interactions and improved pharmacokinetics and safety profiles. This review focuses on the synthetic efforts, design strategies, and structure–activity relationship of the pyrimidine scaffold-based dual kinase inhibitors developed with anticancer potential within the recent 6 years (2018‒2023). Collectively, these strategies are expected to offer fresh perspectives on the future directions of pyrimidine-based dual-target kinase drug design, potentially advancing cancer therapeutics.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996781","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