Archiv der Pharmazie最新文献_第10页

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 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.</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 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 (12a–z), exploring their antioxidant and antimicrobial potential. Notably, compound 12c 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 12a and 12b as standout candidates, showcasing strong antibacterial and antifungal properties through disc-diffusion and broth dilution methods. These promising bioactivities underscore the potential of 12a, 12b and 12c 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.</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

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":"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.","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 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 O-dialkylaminoalkyl substitutions were designed and synthesized. Most of the synthesized compounds showed improved TopoIIα inhibitory and antiproliferative activities. 20 with the best TopoIIα inhibitory activity also exhibited excellent antiproliferative activity with IC50 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 (IC50 11.42 ± 0.82, 7.63 ± 0.46, and 6.15 ± 0.43 μM, respectively). Meanwhile, 20 exhibited weak toxicity to normal cells. In addition, 20 exerted anti-migration and anti-invasion activity against MDA-MB-231 cells. Our results supported that 20 might act as TopoIIα inhibitor with the potential to become a new type of antitumor drug lead.</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 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.</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

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

Assessment of the Phenolics Content in Epilobium angustifolium and Epilobium hirsutum Extracts and Their Pharmacological Activity

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-13 DOI: 10.1002/ardp.202400765

Kateryna Uminska, Michal Korinek, Liudas Ivanauskas, Mohamed El-Shazly, Victoriya Georgiyants, Yu-Li Chen, Monu Kumar Shukla, Sedin Renadi, Tsong-Long Hwang, Fang-Rong Chang, Olha Mykhailenko

{"title":"Assessment of the Phenolics Content in Epilobium angustifolium and Epilobium hirsutum Extracts and Their Pharmacological Activity","authors":"Kateryna Uminska, Michal Korinek, Liudas Ivanauskas, Mohamed El-Shazly, Victoriya Georgiyants, Yu-Li Chen, Monu Kumar Shukla, Sedin Renadi, Tsong-Long Hwang, Fang-Rong Chang, Olha Mykhailenko","doi":"10.1002/ardp.202400765","DOIUrl":"https://doi.org/10.1002/ardp.202400765","url":null,"abstract":"<div>\u0000 \u0000 The recent outbreak of Omicron strains of coronavirus disease urged the search for novel treatments from natural products such as Epilobium species. The present work reports a comparative HPLC-DAD study of the polyphenolic composition of the crude extracts of Epilobium angustifolium and Epilobium hirsutum. Oenothein B, gallic acid, hyperoside, and isoquercitin were the dominant phenolic compounds. E. hirsutum methanol extract showed a high radical scavenging activity as demonstrated by the HPLC-ABTS assay due to its richness in phenolic compounds. The polysaccharide-rich extracts and water extracts of E. hirsutum showed potent anti-coronavirus SARS-CoV-2 activity against the Omicron strain at 10 μg/mL with inhibition percentages of 38.4% and 46.1%, respectively. In contrast, the methanol (50% v/v) extract was inactive. Rutin and chlorogenic acid docked well into the binding pocket of the coronavirus spike protein. Emerging evidence suggests that suppressing excessive neutrophilic inflammation during the late stage of coronavirus infection benefits patients’ survival. The methanol extracts of both plants completely inhibited fMLF/CB-induced elastase release in human neutrophils at 10 μg/mL (IC50 2.44 μg/mL), while the water extract showed an IC50 of 5.67 μg/mL. While several compounds docked well into the spike protein, the major and marker compound oenothein B showed promising in vitro anti-coronavirus activity with an IC50 of 6.08 µM in hACE2-overexpressing HEK293 cells, mimicking the entry of wild-type SARS-CoV-2 into human host cells. The results indicated that E. hirsutum might be helpful in the treatment of coronavirus infections and related inflammatory syndromes.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944719","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, In Vitro Evaluation, and Molecular Docking Studies of Novel 3,5-Diphenyl-1H-1,2,4-Triazole Derivatives as Potential hEGFR Inhibitors

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-13 DOI: 10.1002/ardp.70007

Yakup Kolcuoglu, Olcay Bekircan, Narin Ustalar, Aslı Türe, Atilla Akdemir, Senay Hamarat Sanlier

{"title":"Synthesis, In Vitro Evaluation, and Molecular Docking Studies of Novel 3,5-Diphenyl-1H-1,2,4-Triazole Derivatives as Potential hEGFR Inhibitors","authors":"Yakup Kolcuoglu, Olcay Bekircan, Narin Ustalar, Aslı Türe, Atilla Akdemir, Senay Hamarat Sanlier","doi":"10.1002/ardp.70007","DOIUrl":"https://doi.org/10.1002/ardp.70007","url":null,"abstract":"EGFR, an important target in cancer chemotherapy, is an important component of the signaling system that regulates important cellular processes such as growth, differentiation, metabolism, and apoptosis in response to both internal and external stimuli. Based on this approach, comprehensive modeling studies targeting the EGFR protein were performed, and synthesized molecules were proposed. For this purpose, the synthesis of new 3,5-diphenyl-1H-1,2,4-triazole derivatives containing semicarbazide, thiosemicarbazide, 1,2,4-triazole-3-thione, and 1,2,4-triazole-3-one units was carried out. Among these compounds, 6a–6i presented in the present study exhibited EGFR inhibition in the nanomolar range. In addition, molecules 5e and 6e showed significant IC50 values. Compound 6e showed the closest IC50 value to gefitinib, a well-known EGFR inhibitor, with its noncompetitive inhibition mode. The Ki value of compound 6e was determined as 0.174 µM.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944718","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

Alkyl Tail Variation on Chalcone-Based Quaternary Pyridinium Salts as Rule-of-Thumb for Antimicrobial Activity 基于查尔酮的季吡啶盐的烷基尾变化作为抗菌活性的经验法则

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-11 DOI: 10.1002/ardp.70003

Francesca Seghetti, Riccardo Ocello, Alessandra Bisi, Matteo Masetti, Silvia Gobbi, Federico Falchi, Giovanna Angela Gentilomi, Francesca Bonvicini, Federica Belluti

{"title":"Alkyl Tail Variation on Chalcone-Based Quaternary Pyridinium Salts as Rule-of-Thumb for Antimicrobial Activity","authors":"Francesca Seghetti, Riccardo Ocello, Alessandra Bisi, Matteo Masetti, Silvia Gobbi, Federico Falchi, Giovanna Angela Gentilomi, Francesca Bonvicini, Federica Belluti","doi":"10.1002/ardp.70003","DOIUrl":"https://doi.org/10.1002/ardp.70003","url":null,"abstract":"Aiming at developing a new class of quaternary pyridinium salts, the lead compound 1, characterized by a pyridine-3-yl chalcone framework, was rationally modified by inserting alkyl functions varying from 6 to 18 carbon units. Among the set, some valuable lead compounds were identified. Derivatives 4–6 were primarily active against Staphylococcus aureus and Candida albicans, respectively (MIC = 1.56 and 3.125 μM). In comparison, analogs 4 and 5 showed significant activities against Escherichia coli (MIC = 6.25 μM). Interestingly, the antimicrobial property of compounds 4–6, as well as their antibiofilm activity, occurred at lower concentrations than their cyto- and erythrocyte toxicities, thus ensuring a favorable safety profile. Structure–activity relationship analysis highlighted the critical role of the alkyl tail length in the antimicrobial activity, and optimal results were observed for moieties ranging from 10 to 14 carbon units. Molecular dynamics studies performed on 2 and 5 by modeling them on Gram-positive and Gram-negative membranes showed that the derivatives, upon diffusing across periodic boundary conditions, were able to intercalate into the microbial membranes. The difference in diffusion rates provides useful information to support the diverse antimicrobial potencies of the newly designed quaternary pyridinium salt.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939114","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