Archiv der Pharmazie最新文献_第4页

Design, synthesis of novel thiazole-thiomorpholine derivatives and evaluation of their anticancer activity via in vitro and in silico studies

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-10 DOI: 10.1002/ardp.202400821

Sam Dawbaa, Asaf Evrim Evren, Demokrat Nuha, Halide Edip Temel, Gülşen Akalin Çiftçi, Leyla Yurttaş

{"title":"Design, synthesis of novel thiazole-thiomorpholine derivatives and evaluation of their anticancer activity via in vitro and in silico studies","authors":"Sam Dawbaa, Asaf Evrim Evren, Demokrat Nuha, Halide Edip Temel, Gülşen Akalin Çiftçi, Leyla Yurttaş","doi":"10.1002/ardp.202400821","DOIUrl":"https://doi.org/10.1002/ardp.202400821","url":null,"abstract":"Continuous efforts are carried out to find new cancer treatments. Compounds including thiazole or thiomorpholine rings showed favorable biological activities for various diseases including cancer. In this study, a new series of 4-(4-{[2-(4-phenylthiazol-2-yl)hydrazono]methyl}phenyl)thiomorpholine derivatives were synthesized and tested in vitro for their anticancer activity. Twelve compounds including various 4-phenylthiazol and a single 4-(2-naphthyl)thiazole derivatives were synthesized and analyzed by 1H-nuclear magnetic resonance (NMR), 13C-NMR, and high-resolution mass spectrometry (HRMS). The cytotoxic effects of the compounds were tested on the A549 lung cancer cell line and the L929 healthy cell line. Six compounds (3a, 3b, 3c, 3d, 3e, and 3f) showed better inhibitory activity against A549 cells than the reference drug cisplatin. Compound 3f (4-CH3 phenyl derivative) was the most potent with an IC50 of 3.72 µM. The cytotoxic activity against the healthy cell line L929 was evaluated and all of the tested compounds displayed IC50 values of more than 500 µM, indicating a selectivity toward the cancer cell line A549. Activity against matrix metalloproteinase-9 was also tested and the result indicated a %inhibition of 68.02 and 52.77 for compounds 3g and 3j, respectively. In silico evaluation was achieved via Density Functional Theory calculations and molecular dynamic simulations and the results were in line with those of the in vitro tests.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581683","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

Design, synthesis, biological evaluation, and X-ray single crystal structure of novel computer-aided-drug-designbased α-mangostin derivatives: Multifunctional ligands against Alzheimer's disease

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-10 DOI: 10.1002/ardp.202400671

Quanzhen Chen, Xiangyu Li, Wenting Xiao, Yiyi Sun, Rui Shen, Xiaodi Kou, Aihong Yang

{"title":"Design, synthesis, biological evaluation, and X-ray single crystal structure of novel computer-aided-drug-designbased α-mangostin derivatives: Multifunctional ligands against Alzheimer's disease","authors":"Quanzhen Chen, Xiangyu Li, Wenting Xiao, Yiyi Sun, Rui Shen, Xiaodi Kou, Aihong Yang","doi":"10.1002/ardp.202400671","DOIUrl":"https://doi.org/10.1002/ardp.202400671","url":null,"abstract":"Multifunctional ligand design strategy may be a promising approach for the treatment of Alzheimer's disease (AD). α-Mangostin (α-M), a natural small molecule with anti-AD properties, was used as the lead compound for the design and synthesis of six α-M derivatives (1–6) with the help of computer-aided-drug-design (CADD). Both theoretical calculations and experimental results suggested that 1–6 might serve as promising selective butyrylcholinesterase (BuChE) inhibitors and amyloid-β (Aβ) aggregation inhibitors. Meanwhile, experimental results confirmed the high selectivity of the derivatives, in which 1 had the best inhibitory activity and selectivity on BuChE (IC50 = 0.016 µM, SI = 700.63). The experimental results also showed that 1–6 could act as copper chelators and reactive oxygen species (ROS) scavengers. Furthermore, in vivo experiments with Caenorhabditis elegans also showed that 1 could scavenge ROS and inhibit Aβ aggregation. Notably, single crystals of 1, 4, and the 4-Cu(II) complex were prepared for the first time, which provided a reliable structural basis for analyzing the structure–activity relationship. The dimethylamino derivatives (1, 4) of α-M showed the best activities and were expected to become promising candidate drugs for multifunctional anti-AD.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581528","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

Vitamin D promotes anticancer effects of low-concentration cisplatin-treated non-small cell lung cancer cells via inhibiting the JAK2/STAT3 and TGF-β/SMAD4 pathways

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-10 DOI: 10.1002/ardp.202400933

Heba Effat, Rehab S. Abohashem, Marwa Sharaky, Mohammed Aly Mohammed

{"title":"Vitamin D promotes anticancer effects of low-concentration cisplatin-treated non-small cell lung cancer cells via inhibiting the JAK2/STAT3 and TGF-β/SMAD4 pathways","authors":"Heba Effat, Rehab S. Abohashem, Marwa Sharaky, Mohammed Aly Mohammed","doi":"10.1002/ardp.202400933","DOIUrl":"https://doi.org/10.1002/ardp.202400933","url":null,"abstract":"Lung cancer is one of the most fatal kinds of cancer, with low survival rate because of delayed discovery and traditional therapy failure. This study intends to determine whether cisplatin plus vitamin D could be a more successful combination than standard monotherapy for non-small-cell lung cancer (NSCLC) by targeting the transforming growth factor beta (TGF-β)/mothers against decapentaplegic homolog 4 (SMAD4) and janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways and their downstream targets. Cytotoxic effects of vitamin D on MCF-7, MCFR-10, H1299, A549, and PC3 cell lines were evaluated by sulforhodamine-B (SRB) assay, indicating that H1299 and A549 were the most effected cell lines; hence, they were selected for more investigation. IC50 values of cisplatin against H1299 and A549 cells were established. Quantitative polymerase chain reaction (qPCR) was used to assess the expression levels of JAK2, STAT3, TGF-β, Smad4, matrix metalloproteinase-2 (MMP-2), and MMP-9 in both cell lines treated with vitamin D, cisplatin, or both. Results demonstrated remarkable expression of the aforementioned genes in H1299 and A549 cells, which was sharply decreased once the combination treatment was administered. Additionally, the protein expression of VEGF, MMP9, and angiotensin I, II is considerably inhibited by this combination. According to the obtained data, vitamin D and cisplatin combination therapy can target genes and proteins involved in cell adhesion, migration, and invasion.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581591","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 (3/2025)

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-04 DOI: 10.1002/ardp.2570003

引用次数: 0

First in class pyrrolo[2,3-d]pyrimidine derivatives fused to fluorobenzylpiperidines as dual ligands of acetylcholinesterase and histamine H3 receptor

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-04 DOI: 10.1002/ardp.202400387

Tito Añazco, Tobias Werner, Maria José Torres, María Fernanda Hornos-Carneiro, Joaquín Fernández, Aleksandra Zivkovic, Cristian O. Salas, Alejandro Castro-Álvarez, Margarita Gutiérrez, Holger Stark, Christian Espinosa-Bustos

{"title":"First in class pyrrolo[2,3-d]pyrimidine derivatives fused to fluorobenzylpiperidines as dual ligands of acetylcholinesterase and histamine H3 receptor","authors":"Tito Añazco, Tobias Werner, Maria José Torres, María Fernanda Hornos-Carneiro, Joaquín Fernández, Aleksandra Zivkovic, Cristian O. Salas, Alejandro Castro-Álvarez, Margarita Gutiérrez, Holger Stark, Christian Espinosa-Bustos","doi":"10.1002/ardp.202400387","DOIUrl":"https://doi.org/10.1002/ardp.202400387","url":null,"abstract":"Alzheimer's disease (AD) is a multifactorial neurodegenerative disease with manifold underlying pathophysiological mechanisms. Therefore, multitarget-directed ligands potentially offer beneficial therapeutic effects compared with classical therapies. Dual targeting of the histamine H3 receptor (H3R) and acetylcholinesterase (AChE) is a valid strategy for the treatment of AD. In this work, a new series of pyrrolo[2,3-d]pyrimidines fused to fluorobenzylpiperidine derivatives was designed, synthesized, and pharmacologically evaluated. Among the 16 derivatives reported here, compounds 4a (IC50 = 2.19 µM for human acetylcholinesterase (hAChE) and Ki = 1.05 µM for H3R) and 4f (IC50 = 4.27 µM for hAChE and Ki = 1.31 µM for H3R) show the most balanced dual targeting behavior coupled with moderate affinities at both targets. Selected compounds showed medium inhibition of butyrylcholinesterase (BuChE). Moreover, these compounds did not show any toxicity in the SH-SY5Y or HEK-293 cell lines at pharmacologically relevant concentrations. In silico studies allowed the proposition of binding modes and the prediction of favorable absorption, distribution, metabolism and excretion properties. The cumulative results suggest compounds 4a and 4f as lead structures for the further development of novel dual-targeted ligands for AD therapy.","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":"143554670","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 anti-Acinetobacter baumannii therapeutic potential of azole hybrids: A mini-review

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-04 DOI: 10.1002/ardp.202400592

Zhi Xu, Junna Liu, Yafei Zhuang

{"title":"The anti-Acinetobacter baumannii therapeutic potential of azole hybrids: A mini-review","authors":"Zhi Xu, Junna Liu, Yafei Zhuang","doi":"10.1002/ardp.202400592","DOIUrl":"https://doi.org/10.1002/ardp.202400592","url":null,"abstract":"Acinetobacter baumannii is one of the major causes of severe hospital- and community-acquired infections, posing a significant threat to human lives. A. baumannii has already generated resistance to almost all of the currently available antibiotics, but no new class of antibacterials have been launched for the treatment of infections caused by A. baumannii in the last half century, creating an urgent need to develop novel antibacterials. Azoles as a broad class of five-membered nitrogen-containing aromatic heterocycles are privileged pharmacophores widely found in pharmaceuticals. Azoles could target on diverse enzymes, proteins, and receptors in A. baumannii via various noncovalent interactions. Particularly, azole hybrids have potential advantages in increasing therapeutic efficacy and circumventing drug resistance, representing useful scaffolds for the discovery of novel anti-A. baumannii agents. This review outlines the current scenario of the antibacterial therapeutic potential of azole hybrids against A. baumannii, developed from 2020 onwards, aiming to provide potential candidates for further preclinical/clinical evaluations and facilitate the rational design of more effective candidates.","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":"143554217","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

Discovery of a novel 2,4-thiazolidinedione derivative as dual inhibitor of β-catenin/TCF4 interaction and tubulin polymerization in colon cancer cells

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-04 DOI: 10.1002/ardp.202400796

Yating Guo, Meng Cao, Zhaohui Li, Hongfei Zhou, Zhuo Chen, Qianbin Li

{"title":"Discovery of a novel 2,4-thiazolidinedione derivative as dual inhibitor of β-catenin/TCF4 interaction and tubulin polymerization in colon cancer cells","authors":"Yating Guo, Meng Cao, Zhaohui Li, Hongfei Zhou, Zhuo Chen, Qianbin Li","doi":"10.1002/ardp.202400796","DOIUrl":"https://doi.org/10.1002/ardp.202400796","url":null,"abstract":"Hyperactivation of the Wnt/β-catenin signaling pathway has been widely recognized as a pathogenic mechanism for colorectal cancer (CRC). Based on a previously reported lead compound, iCRT14, a series of 2,4-thiazolidinedione derivatives were designed, synthesized, and evaluated in vitro for their antiproliferative activity against colon cancer cells. Compound 15k exhibited the most potent activity against the HCT116 and SW480 cell lines. Compound 15k inhibited Wnt/β-catenin signaling by disrupting the protein–protein interactions between β-catenin and TCF4. Compound 15k simultaneously inhibited tubulin polymerization, disorganized the microtubule network, and arrested the cell cycle at the G2/M phase, offering an additional mechanism of action and 15k induced cell apoptosis by activating caspase-3 and poly(ADP-ribose) polymerase. Additionally, compound 15k inhibited cell migration without affecting the levels of β-catenin protein. These results offer guidance for developing the current series as potential new anticancer therapeutics.","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":"143554218","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

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