Archiv der Pharmazie最新文献_第3页

Xylazine as an emerging new psychoactive substance; focuses on both 5-HT7 and κ-opioid receptors' molecular interactions and isosteric replacement 赛拉嗪作为一种新兴的精神活性物质；重点研究 5-HT7 和 κ-阿片受体的分子相互作用和同工异构替代作用

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-17 DOI: 10.1002/ardp.202500041

Giuseppe Floresta, Alberto Granzotto, Vincenzo Patamia, Davide Arillotta, Gabriele D. Papanti, Amira Guirguis, John M. Corkery, Giovanni Martinotti, Stefano L. Sensi, Fabrizio Schifano

{"title":"Xylazine as an emerging new psychoactive substance; focuses on both 5-HT7 and κ-opioid receptors' molecular interactions and isosteric replacement","authors":"Giuseppe Floresta, Alberto Granzotto, Vincenzo Patamia, Davide Arillotta, Gabriele D. Papanti, Amira Guirguis, John M. Corkery, Giovanni Martinotti, Stefano L. Sensi, Fabrizio Schifano","doi":"10.1002/ardp.202500041","DOIUrl":"https://doi.org/10.1002/ardp.202500041","url":null,"abstract":"Xylazine, traditionally used as a veterinary sedative, has recently emerged as a new psychoactive substance, being typically ingested in combination with fentanyl derivatives and hence raising significant public health concerns. Despite its increasing prevalence, little is known about its molecular interactions with human neuroreceptors, specifically the serotonin 7 (5-HT7R) and kappa-opioid (KOR) receptors, which play critical roles in mood regulation, consciousness and nociception. Hence, the binding affinity and molecular interactions of xylazine with both 5-HT7R and KOR through docking simulations and molecular dynamics calculations were investigated. These computational approaches revealed critical insights into receptor binding motifs and highlighted structural modifications that could enhance receptor affinity. The isosteric replacements within the xylazine structure to improve its binding efficacy were assessed, demonstrating that minimal structural modifications can potentiate its interaction with 5-HT7R and KOR. These findings may well advance our understanding of xylazine's mechanism of action, possibly contributing to identifying suitable treatment/management approaches in treating xylazine-related overdoses.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202500041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632644","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

The current landscape of 1,2,3-triazole hybrids with anticancer therapeutic potential: Part I

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-13 DOI: 10.1002/ardp.202500001

Shanshan Huang, Zhi Xu, Yafei Zhuang

{"title":"The current landscape of 1,2,3-triazole hybrids with anticancer therapeutic potential: Part I","authors":"Shanshan Huang, Zhi Xu, Yafei Zhuang","doi":"10.1002/ardp.202500001","DOIUrl":"https://doi.org/10.1002/ardp.202500001","url":null,"abstract":"Cancer, with its steadily increasing morbidity and mortality, will continue to pose a threat to humanity over an extended period. Chemotherapeutics play an indispensable role in cancer treatment, and hundreds of drugs have been approved for this purpose. Nevertheless, the fight against cancer remains a formidable challenge. This is mainly due to the emergence of multidrug resistance and the severe side effects associated with currently available anticancer drugs. Consequently, there is an urgent imperative to explore novel chemotherapeutic agents. 1,2,3-Triazoles belong to one of the most privileged classes of nitrogen-containing five-membered heterocycles and are regarded as prominent sources for the development of innovative anticancer chemotherapeutics. 1,2,3-Triazole hybrids, which possess multitargeted mechanisms of action within the cancer progression pathway, hold the potential to overcome multidrug resistance and mitigate side effects. Furthermore, several 1,2,3-triazole hybrids have already been approved for cancer therapy or are currently under clinical evaluation. This clearly demonstrates that 1,2,3-triazole hybrids are valuable scaffolds in the treatment and eradication of cancer. This review aims to provide insights into the anticancer therapeutic potential of 1,2,3-triazole hybrids, along with their mechanisms of action, crucial aspects of design, and structure–activity relationships (SARs). It encompasses articles published from 2021 onward.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602533","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

Research progress of cycloartane triterpenoids and pharmacological activities

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-12 DOI: 10.1002/ardp.202400923

Chen Wang, Xiaodong Mu, Jingyong Sun

引用次数: 0

Novel derivatives of thiohydantoin-containing tetrahydro-β-carboline possess activity against influenza virus at late stages of viral cycle without affecting viral neuraminidase

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-12 DOI: 10.1002/ardp.202400733

Derenik S. Khachatryan, Vasiliy N. Osipov, Anton V. Kolotaev, Svetlana K. Belus, Karine R. Matevosyan, Iana L. Esaulkova, Shokhrukh A. Khasanov, Polina A. Ilyina, Alexandrina S. Volobueva, Edward S. Ramsay, Vladimir V. Zarubaev

{"title":"Novel derivatives of thiohydantoin-containing tetrahydro-β-carboline possess activity against influenza virus at late stages of viral cycle without affecting viral neuraminidase","authors":"Derenik S. Khachatryan, Vasiliy N. Osipov, Anton V. Kolotaev, Svetlana K. Belus, Karine R. Matevosyan, Iana L. Esaulkova, Shokhrukh A. Khasanov, Polina A. Ilyina, Alexandrina S. Volobueva, Edward S. Ramsay, Vladimir V. Zarubaev","doi":"10.1002/ardp.202400733","DOIUrl":"https://doi.org/10.1002/ardp.202400733","url":null,"abstract":"Influenza infection represents a serious challenge for virological surveillance and healthcare systems in all countries globally. Despite obvious success in control of influenza through vaccination and antiviral drug development, this infection remains poorly controlled due to antigenic drift and fast selection of drug-resistant viral variants. The design of novel drugs with alternative targets and mechanisms of action is, therefore, an important goal for medical science worldwide. In the current study, we describe the chemical synthesis of novel tetrahydro-β-carboline derivatives containing a thiohydantoin fragment, as well as their antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1). In general, the library of compounds was of low toxicity. Of the 23 compounds under investigation, 10 (43.5%) displayed a selectivity index (SI) of 10 or higher, their activity strongly exceeding that of the reference compound rimantadine. The most active compounds have also demonstrated suppressing activity against the phylogenetically distinct influenza virus of type B. These compounds, similar to the reference compound zanamivir, were active at very late stages of the viral cycle (4–6 h postinfection), suggesting interference with processes of virion assembly and budding. However, no direct inhibiting activity against viral neuraminidase has been demonstrated. The results obtained can be considered as a rationale for further structural optimization and study of this group as potential broad-range antivirals effective against influenza viruses.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602632","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

Anticholinesterase and carbonic anhydrase inhibitory activities of natural carnosic acid derivatives: A comprehensive in vitro and in silico study

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-12 DOI: 10.1002/ardp.202400909

Zeynep Köksal, Halil Şenol

{"title":"Anticholinesterase and carbonic anhydrase inhibitory activities of natural carnosic acid derivatives: A comprehensive in vitro and in silico study","authors":"Zeynep Köksal, Halil Şenol","doi":"10.1002/ardp.202400909","DOIUrl":"10.1002/ardp.202400909","url":null,"abstract":"This study investigates the anticholinesterase (acetylcholinesterase [AChE] and butyrylcholinesterase [BChE]) and carbonic anhydrase (CAI and CAII) inhibitory activities of carnosic acid and its natural derivatives, including carnosol, rosmanol, 7-methoxy-rosmanol, 12-methoxy-carnosic acid, and isorosmanol. Among the tested compounds, rosmanol demonstrated exceptional potency, with IC50 values of 0.73 nM for AChE and 0.75 nM for BChE, significantly outperforming tacrine. Rosmanol also exhibited remarkable inhibition of CA I (IC50 = 0.21 nM), surpassing acetazolamide by over 450-fold, and moderate inhibition of CAII. Molecular docking and molecular mechanics generalized born surface area (MM-GBSA) studies revealed strong binding affinities for rosmanol, with docking scores of −11.757 kcal/mol (AChE) and −11.465 kcal/mol (BChE). The MM-GBSA binding free energy calculations further confirmed stable interactions for CA I (−63.24 kcal/mol) and AChE (−60.09 kcal/mol). Molecular dynamics simulations over 50 ns showed stable enzyme-ligand complexes, particularly for AChE and BChE (root mean square deviation ~1.5 Å), with key residues identified as crucial for stabilization. Other derivatives also displayed significant inhibitory activities, suggesting their potential as secondary leads. The ADMET analysis showed favorable pharmacokinetics and rosmanol emerged as a promising candidate. This comprehensive study highlights rosmanol as a multitarget therapeutic agent with potent anticholinesterase and CA inhibitory properties, offering promise for treating neurodegenerative and metabolic disorders.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202400909","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600079","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 novel substituted s-triazines tethered benzenesulfonamides as potential antimicrobial candidates: Antibiofilm and bacterial protein permeability assessments

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-10 DOI: 10.1002/ardp.202400931

Ahmed A. Al-Karmalawy, Haytham O. Tawfik, Gharieb S. El-Sayyad, Ayman Abo Elmaaty, Sobhy S. Abdel-Fatah, Akhtar Atiya, Abdullah Yahya Abdullah Alzahrani, Arwa Omar Al Khatib, Mervat H. El-Hamamsy, Heba A. Elsebaie

{"title":"Design and synthesis of novel substituted s-triazines tethered benzenesulfonamides as potential antimicrobial candidates: Antibiofilm and bacterial protein permeability assessments","authors":"Ahmed A. Al-Karmalawy, Haytham O. Tawfik, Gharieb S. El-Sayyad, Ayman Abo Elmaaty, Sobhy S. Abdel-Fatah, Akhtar Atiya, Abdullah Yahya Abdullah Alzahrani, Arwa Omar Al Khatib, Mervat H. El-Hamamsy, Heba A. Elsebaie","doi":"10.1002/ardp.202400931","DOIUrl":"https://doi.org/10.1002/ardp.202400931","url":null,"abstract":"New s-triazine hydrazone hybrids (4a–4r) were designed and synthesized as promising microbial DNA gyrase inhibitors. This was done by taking the lead DNA gyrase inhibitor (AstraZeneca arylaminotriazine) as a reference. The novel samples were subsequently tested as antimicrobial agents against certain pathogenic bacteria and unicellular fungi. The antibiofilm potential and the membrane leakage test were used to determine the mechanism of the antimicrobial response. The minimum inhibitory concentration (MIC) values of 4g, 4i, and 4r samples were between 62.5 and 250.0 µg/mL. The MIC values for the 4g candidate against Staphylococcus aureus, Candida albicans, Enterobacter agglomerans, and Klebsiella pneumonia are 62.5, 125.0, and 250.0 µg/mL, respectively. Conversely, the MIC of compound 4i was 62.5 µg/mL for C. albicans and E. agglomerans and 125.0 µg/mL for S. aureus and K. pneumonia. Besides, a molecular docking study was performed to validate both the binding affinity and binding mode of the newly designed analogs of s-triazine candidates toward bacterial DNA gyrase receptors. The synthesized nanocomposites had promising antimicrobial potentials, which are encouraging their use in biomedical applications. Consequently, the afforded compounds can be employed as promising antimicrobial lead compounds for future optimization.","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":"143581592","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 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