Archiv der Pharmazie最新文献

Aripiprazole as an Inhibitor of the EGFR/PI3K/AKT Signaling Pathway and Sensitizer of MPA Suppressed Progestin-Resistant Endometrial Cancer Cells 阿立哌唑作为EGFR/PI3K/AKT信号通路抑制剂和MPA抑制孕激素抵抗子宫内膜癌细胞的增敏剂

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-25 DOI: 10.1002/ardp.70017

Wen Gan, Xinyu Liu, Yikang Zhou, Wei Gu, Xiaohu Liu, Lingyi Song, Jian Li, Yudong Wang, Fei Mao

{"title":"Aripiprazole as an Inhibitor of the EGFR/PI3K/AKT Signaling Pathway and Sensitizer of MPA Suppressed Progestin-Resistant Endometrial Cancer Cells","authors":"Wen Gan, Xinyu Liu, Yikang Zhou, Wei Gu, Xiaohu Liu, Lingyi Song, Jian Li, Yudong Wang, Fei Mao","doi":"10.1002/ardp.70017","DOIUrl":"https://doi.org/10.1002/ardp.70017","url":null,"abstract":"<div>\u0000 \u0000 <p>Drug repurposing, which involves applying existing pharmaceuticals to new therapeutic areas, offers several advantages, including increased efficiency, reduced costs, and lower risks. The research aimed to investigate the molecular mechanisms underlying the new application of the antipsychotic drug aripiprazole (APZ) in the treatment of endometrial cancer (EC), as well as its synergistic efficacy when used in combination with progestin. The cell viability assay and proliferation assay demonstrated that APZ exerted a significant inhibitory effect on the proliferation of ISK and KLE cells. Moreover, APZ was found to induce cell apoptosis prominently by flow cytometry. Network pharmacology analysis indicated that the anti-EC effects of APZ were mediated via the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which was subsequently confirmed by Western blot analysis. Furthermore, APZ significantly enhanced the proliferation inhibitory effect of medroxyprogesterone acetate (MPA) against progestin-resistant KLE cells, displaying remarkable synergistic activity. These findings position APZ as a promising therapeutic candidate for EC, with potential utility both as a monotherapy and in combination with MPA, offering new avenues for EC treatment strategies.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135640","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

Synthesis, Characterization and Evaluation of Antioxidant and Antimicrobial Activities of Novel Isatin Derivatives 新型Isatin衍生物的合成、表征及抗氧化抗菌活性评价

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-25 DOI: 10.1002/ardp.70014

Komal Rathi, Divya Kumari, Priyanka Yadav, Varun Rawat, Pracheta Janmeda, Ved Prakash Verma

{"title":"Synthesis, Characterization and Evaluation of Antioxidant and Antimicrobial Activities of Novel Isatin Derivatives","authors":"Komal Rathi, Divya Kumari, Priyanka Yadav, Varun Rawat, Pracheta Janmeda, Ved Prakash Verma","doi":"10.1002/ardp.70014","DOIUrl":"https://doi.org/10.1002/ardp.70014","url":null,"abstract":"<div>\u0000 \u0000 <p>The pursuit of multifunctional therapeutic agents remains crucial in combating oxidative stress and microbial resistance. In this study, we synthesized and characterized a diverse series of novel isatin-based derivatives (<b>12a–z</b>), exploring their antioxidant and antimicrobial potential. Notably, compound <b>12c</b> demonstrated remarkable antioxidant efficacy among all isatin-based derivatives, with an IC₅₀ value of 9.79 ± 0.168 µg/mL in the DPPH radical scavenging assay, positioning it as a potent radical scavenger comparable to the standard (ascorbic acid). Furthermore, antimicrobial screening identified compounds <b>12a</b> and <b>12b</b> as standout candidates, showcasing strong antibacterial and antifungal properties through disc-diffusion and broth dilution methods. These promising bioactivities underscore the potential of <b>12a</b>, <b>12b</b> and <b>12c</b> as therapeutic agents, meriting further investigation for their application in oxidative stress-related conditions and infectious disease management. This study lays the groundwork for future development of isatin derivatives as pharmacologically relevant molecules in both antioxidant and antimicrobial domains.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135663","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

The Quest for Ligands Against Kinesin Motor Protein Eg5 寻找对抗运动蛋白Eg5的配体

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-22 DOI: 10.1002/ardp.70010

Ahmet Fatih Sahin, Simone Carradori, Alessia Ricci, Muhammad Rashad, Atilla Akdemir

{"title":"The Quest for Ligands Against Kinesin Motor Protein Eg5","authors":"Ahmet Fatih Sahin, Simone Carradori, Alessia Ricci, Muhammad Rashad, Atilla Akdemir","doi":"10.1002/ardp.70010","DOIUrl":"https://doi.org/10.1002/ardp.70010","url":null,"abstract":"<div>\u0000 \u0000 <p>The Kinesin Eg5 motor protein is essential for the formation of the mitotic spindles and chromosome segregation, which is necessary for cell division. The inhibition of Eg5 has emerged as a potential therapeutic strategy for inhibiting the uncontrolled proliferation of cancer cells. This study aims to identify inhibitors targeting the allosteric site I of Eg5. To this end, a hierarchical virtual screening was applied to screen the ZINC20-Anodyne compound library comprising approximately 11 million druglike compounds. The procedure includes a shape similarity screening, a pharmacophore screening, docking studies with subsequent re-scorings, molecular dynamics simulations, and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) binding free energy calculations and resulted in the selection of four compounds for Eg5 inhibition assays. One compound displays an IC<sub>50</sub> value of 29 µM, while the remaining three compounds show weaker inhibition of Kinesin Eg5. As such, structurally novel Kinesin Eg5 inhibitors have been obtained for further hit-to-lead optimization programs.</p>\u0000 </div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118020","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

Evernic Acid: A Low-Toxic and Selective Alternative to Chemotherapeutic Agents in the Treatment of Ovarian Cancer Evernic Acid：一种低毒和选择性替代化疗药物治疗卵巢癌

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-22 DOI: 10.1002/ardp.70015

Mine Ensoy, Damla Nur Parıltı, Ayşe Hale Alkan, Kübra Nur Kaplan İlhan, Pelin Mutlu, Bala Gür Dedeoğlu, Demet Cansaran-Duman

{"title":"Evernic Acid: A Low-Toxic and Selective Alternative to Chemotherapeutic Agents in the Treatment of Ovarian Cancer","authors":"Mine Ensoy, Damla Nur Parıltı, Ayşe Hale Alkan, Kübra Nur Kaplan İlhan, Pelin Mutlu, Bala Gür Dedeoğlu, Demet Cansaran-Duman","doi":"10.1002/ardp.70015","DOIUrl":"https://doi.org/10.1002/ardp.70015","url":null,"abstract":"<p>Evernic acid (EA) has emerged as a potential therapeutic agent with its low toxicity and anticancer properties. In this study, the anticancer effect of EA on ovarian cancer cell lines and normal ovarian surface epithelial cells (OSE) was evaluated. The antiproliferative effect of EA was evaluated by xCELLigence Real-Time Cell analysis, colony formation assay, and acridine orange and DAPI staining methods. Genotoxicity analysis was performed by comet assay. The effect of EA on cell migration was analyzed by wound healing assay. The potential of EA to induce apoptosis was also determined by evaluating the changes in gene and protein expression levels by qRT-PCR and Western blot analysis, respectively. EA was found to be a promising potential therapeutic agent for ovarian cancer without showing significant cytotoxic effect on normal cells. Furthermore, EA decreased the ability of ovarian cancer cells for migration, increased the rate of apoptosis by inhibiting BIRC5 and activating CASP3, triggered cell cycle arrest in the G2/M phase, and caused a decrease in mitochondrial membrane potential and genotoxic effects. The results have shown that EA could be an effective candidate molecule for ovarian cancer treatment.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118021","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 and Synthesis of O-Dialkylaminoalkyl Substituted Urolithin Derivatives: DNA Topoisomerase IIα Inhibition With Promising Antiproliferative Activity 邻二烷基氨基取代尿素衍生物的设计与合成：DNA拓扑异构酶ⅱα抑制与有希望的抗增殖活性

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-22 DOI: 10.1002/ardp.70009

Xintong Li, Xiaochun Zhang, Chan Yin, Chunhua Lu, Yuemao Shen

{"title":"Design and Synthesis of O-Dialkylaminoalkyl Substituted Urolithin Derivatives: DNA Topoisomerase IIα Inhibition With Promising Antiproliferative Activity","authors":"Xintong Li, Xiaochun Zhang, Chan Yin, Chunhua Lu, Yuemao Shen","doi":"10.1002/ardp.70009","DOIUrl":"https://doi.org/10.1002/ardp.70009","url":null,"abstract":"<div>\u0000 \u0000 <p>Based on the pharmacophore structural characteristics of topoisomerase II (TopoII) inhibitors: (i) planar polyaromatic skeleton; (ii) the cation core; (iii) a groove-binding side chain moiety, 16 urolithin derivatives with <i>O</i>-dialkylaminoalkyl substitutions were designed and synthesized. Most of the synthesized compounds showed improved TopoIIα inhibitory and antiproliferative activities. <b>20</b> with the best TopoIIα inhibitory activity also exhibited excellent antiproliferative activity with IC<sub>50</sub> values of 0.91 ± 0.01, 1.93 ± 0.04, and 2.84 ± 0.34 μM against the MDA-MB-231, HeLa, and A549 cell lines, being about 12.55, 3.95, and 2.17 times more active than VP-16 (IC<sub>50</sub> 11.42 ± 0.82, 7.63 ± 0.46, and 6.15 ± 0.43 μM, respectively). Meanwhile, <b>20</b> exhibited weak toxicity to normal cells. In addition, <b>20</b> exerted anti-migration and anti-invasion activity against MDA-MB-231 cells. Our results supported that <b>20</b> might act as TopoIIα inhibitor with the potential to become a new type of antitumor drug lead.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108751","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

Erratum: Targeting the Isoprenoid Pathway in Choleste Biosynthesis: An Approach to Identify Isoprenoid Biosynthesis Inhibitors 在胆石生物合成中靶向类异戊二烯途径：一种鉴定类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 : 2025-05-21 DOI: 10.1002/ardp.70016

引用次数: 0

Iron Homeostasis and Metabolism During Pregnancy: Exploring Innovative Drug Delivery Approaches for Treating Iron Deficiency Anemia in Pregnant Women 妊娠期间的铁稳态和代谢：探索治疗孕妇缺铁性贫血的创新药物给药途径

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-19 DOI: 10.1002/ardp.202400983

Vaishali Joshi, Rajendra Awasthi

{"title":"Iron Homeostasis and Metabolism During Pregnancy: Exploring Innovative Drug Delivery Approaches for Treating Iron Deficiency Anemia in Pregnant Women","authors":"Vaishali Joshi, Rajendra Awasthi","doi":"10.1002/ardp.202400983","DOIUrl":"https://doi.org/10.1002/ardp.202400983","url":null,"abstract":"<div>\u0000 \u0000 <p>Pregnant women and small children are more prone to anemia. Even among the most affluent and educated portions of society, an estimated 50% of pregnant women, adolescent girls, and youngsters are anemic. This review recapitulates previous findings exploring advancements in anemia management in pregnant women. The published articles were searched using Google Scholar, Web of Science, Scopus, and Clinical Trials. Primary causes of anemia are an inadequate supply of dietary iron, deficiency of folate due to the lack of vegetable consumption, and thus a lack of vitamin B12, and a lack of dietary iron bioavailability from phytate and fiber-rich diets. When hemoglobin falls below 5 g/dL, the maternal mortality rate multiplies 8–10 times. Early detection and treatment of anemia during pregnancy may minimize maternal mortality, substantially decrease childhood and adolescent nutritional deficiency, and improve adult height. Maternal anemia decreases intrauterine growth, which increases the risk of premature delivery and low birth weight in babies. Intrauterine growth retardation coupled with a low birth weight leads to an inadequate growth trajectory throughout childhood, adolescence, and adulthood. Nano-delivery systems stand out as a promising avenue, utilizing nanotechnology to enhance the absorption of iron. These systems offer targeted delivery of iron supplements, overcoming challenges associated with conventional formulations. The exploration of nanotechnology in iron deficiency anemia treatment marks a significant stride toward developing advanced and tailored solutions for improving iron supplementation.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091262","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

NorA Efflux Pump Inhibitors: Expanding SAR Knowledge of Pyrazolo[4,3-c][1,2]benzothiazine 5,5-Dioxide Derivatives NorA外排泵抑制剂：扩展吡唑啉[4,3-c][1,2]苯并噻嗪5,5-二氧化衍生物的SAR知识

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-19 DOI: 10.1002/ardp.70000

Giada Cernicchi, Alessandra Di Gregorio, Tommaso Felicetti, Elisa Rampacci, Giulia Casari, Tatiana Armeni, Brenda Romaldi, Ermelinda Zefaj, Fabrizio Passamonti, Serena Massari, Giuseppe Manfroni, Maria Letizia Barreca, Oriana Tabarrini, Carla Vignaroli, Stefano Sabatini

{"title":"NorA Efflux Pump Inhibitors: Expanding SAR Knowledge of Pyrazolo[4,3-c][1,2]benzothiazine 5,5-Dioxide Derivatives","authors":"Giada Cernicchi, Alessandra Di Gregorio, Tommaso Felicetti, Elisa Rampacci, Giulia Casari, Tatiana Armeni, Brenda Romaldi, Ermelinda Zefaj, Fabrizio Passamonti, Serena Massari, Giuseppe Manfroni, Maria Letizia Barreca, Oriana Tabarrini, Carla Vignaroli, Stefano Sabatini","doi":"10.1002/ardp.70000","DOIUrl":"https://doi.org/10.1002/ardp.70000","url":null,"abstract":"<p>Antimicrobial resistance (AMR) represents a significant global concern, driven by the overuse of antibiotics. One of the principal mechanisms contributing to AMR is the activity of microbial efflux pumps (EPs), which expel diverse antibiotics out of bacterial cells, thereby rendering them ineffective. Our research aimed to expand the range of molecular classes that inhibit the <i>Staphylococcus aureus</i> EP NorA. In this study, starting from the hit compound pyrazolo[4,3-<i>c</i>][1,2]benzothiazine 5,5-dioxide <b>1</b>, previously reported as a NorA efflux pump inhibitor (EPI), we undertook medicinal chemistry efforts, which involved the iterative combination of the design and synthesis of new analogues with data obtained through ethidium bromide efflux inhibition assays. Subsequent synergistic assays with ciprofloxacin (CPX) against the resistant strain SA-1199B led to the identification of three potent compounds (<b>3</b>, <b>10</b>, and <b>19</b>). The evaluation of these compounds in combination with CPX against NorA-overexpressing and NorA-knockout strains (SA-K2378 and SA-K1902, respectively) confirmed that the observed synergy with CPX is dependent on the presence of NorA. Additionally, the combination of NorA EPIs with CPX reduced biofilm production in NorA-overexpressing strains. These findings enhance our understanding of the structure–activity relationship of pyrazolobenzothiazine derivatives and support the use of EtBr efflux assays for rapid NorA inhibitors' identification.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091263","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 Human Antimicrobial Peptides and Female Reproductive Tract Infections 天然人类抗菌肽与女性生殖道感染

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-16 DOI: 10.1002/ardp.70008

Tong Cheng, Luming Wu, Jijun Tao, Shiyan Tu, Xue Fan, Yixiang Wang, Yiqing Wang

引用次数: 0

The Chemistry and Bioactivity of Mefenamic Acid Derivatives: A Review of Recent Advances 甲氧胺酸衍生物的化学及生物活性研究进展

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-16 DOI: 10.1002/ardp.70004

Hifza Mustafa, Saima Daud, Sabahat Sheraz, Maria Bibi, Tauseef Ahmad, Asma Sardar, Tanzeela Fazal, Asma Khan, Obaid-ur-Rahman Abid

{"title":"The Chemistry and Bioactivity of Mefenamic Acid Derivatives: A Review of Recent Advances","authors":"Hifza Mustafa, Saima Daud, Sabahat Sheraz, Maria Bibi, Tauseef Ahmad, Asma Sardar, Tanzeela Fazal, Asma Khan, Obaid-ur-Rahman Abid","doi":"10.1002/ardp.70004","DOIUrl":"https://doi.org/10.1002/ardp.70004","url":null,"abstract":"<div>\u0000 \u0000 <p>Mefenamic acid (MA) represents an efficient nonsteroidal anti-inflammatory drug (NSAID) for treatment in many circumstances of painful conditions and inflammation, but its poor water solubility and gastrointestinal side effects often obstruct its clinical application. Consequently, researchers have been conducting studies on the synthesis of prodrugs and heterocyclic compounds as MA derivatives for the improvement of their pharmacological profile. This review discusses an overview of recent developments in the synthesis and biological applications of MA derivatives. It covers several strategies used to modify the chemical structure of MA to pursue pharmacokinetic improvement, solubility, and targeting features, among which are heterocyclic moieties and prodrug design. Following the many synthetically produced derivatives of MA, mainly proposed between classic organic synthesis and more recent methodologies, such as microwave-assisted synthesis and green chemistry protocols, this review will consider how different structural variations are able to influence the assumed pharmacological actions: analgesic, anti-inflammatory, and anticancer. The findings demonstrate significant progress toward the development of safer and more effective NSAID therapies; thus, they support, in a broad and unprecedented way, the potential of MA derivatives and prodrugs in transforming the state of pain management and inflammation treatment.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074521","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