Archiv der Pharmazie最新文献_第9页

Recent Advancements and Developments of Anti-Malarial Agents Reported in 2023 2023年抗疟疾药物的最新进展和发展报告。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-12-11 DOI: 10.1002/ardp.70149

Palak K. Vadodariya, Shahnaz Alom, Anu Sharma, Deepika Kathuria, Neetu Chopra, Tejas M. Dhameliya

{"title":"Recent Advancements and Developments of Anti-Malarial Agents Reported in 2023","authors":"Palak K. Vadodariya, Shahnaz Alom, Anu Sharma, Deepika Kathuria, Neetu Chopra, Tejas M. Dhameliya","doi":"10.1002/ardp.70149","DOIUrl":"10.1002/ardp.70149","url":null,"abstract":"<div>\u0000 \u0000 Malaria, caused by Plasmodium falciparum and other species, remains a significant global health issue, transmitted by infected Anopheles mosquitoes. According to the WHO 2024 report, malaria affected 249 million individuals and resulted in 608,000 deaths between 2000 and 2022. The rise of drug resistance in both Plasmodium species and Anopheles mosquitoes has significantly complicated the malaria treatment, necessitating the development of novel therapeutic agents. This review highlights recent advancements in the design of anti-malarial drugs, with a particular focus on heterocyclic compounds reported in 2023, in continuation of our previous works on updates on anti-malarial agents reported since 2016. Among these, artemisinin derivatives have shown remarkable efficacy, while other heterocyclic classes—such as benzofuran, β-lactam, coumarin, indole, morpholine, piperazine, pyrimidine, pyrrole, quinazoline, quinoline, thiazole, and triazoles—are emerging as promising alternatives. These compounds target essential parasite functions such as heme metabolism, RBC invasion, and oxidative stress pathways, with several new hybrid molecules combining multiple mechanisms of action to counter drug resistance. This review provides an overview of recent developments in these heterocyclic-based anti-malarial agents, summarizing their chemical structures, mechanisms of action, and therapeutic potential. By focusing on innovations reported in 2023, this study aims to orient the ongoing research in the pursuit of safer and more effective treatments for malaria.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740108","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 Rofecoxib-Derived Theranostic Probe and Its Combination With PD-1 Inhibitor for High-Efficiency Cancer Therapy 罗非昔布衍生的治疗探针及其与PD-1抑制剂联合用于高效癌症治疗。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-12-11 DOI: 10.1002/ardp.70155

Xinli Wang, Xia Wang, Xuejing Su, Zexin Wang, Yongxiao Sun, Lijun Xie, Xiaoyan Lin

引用次数: 0

Phenylvinylsulfonate-Anchored Azetidin-2-ones as Potent Antibacterial Agents: ROS-Mediated Mechanism, Selective Cytotoxicity, and In Silico Target-Interaction Studies 苯基乙烯基磺酸锚定氮杂苷-2- 1作为有效的抗菌剂：ros介导的机制、选择性细胞毒性和硅靶相互作用研究

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-12-04 DOI: 10.1002/ardp.70163

Shalu Thakur, Rohit Sharma, Nishima Wangoo, Aman Bhalla

{"title":"Phenylvinylsulfonate-Anchored Azetidin-2-ones as Potent Antibacterial Agents: ROS-Mediated Mechanism, Selective Cytotoxicity, and In Silico Target-Interaction Studies","authors":"Shalu Thakur, Rohit Sharma, Nishima Wangoo, Aman Bhalla","doi":"10.1002/ardp.70163","DOIUrl":"https://doi.org/10.1002/ardp.70163","url":null,"abstract":"<div>\u0000 \u0000 The rise of multidrug-resistant pathogens, including MRSA, underscores the urgent need for novel antibacterial agents with minimum resistance potential and enhanced potency. Herein, we report the design and synthesis of novel phenylvinylsulfonate-anchored azetidin-2-ones 8a–h & 9i–j via the reaction of (E)-2-phenylethene-1-sulfonyl chloride with differently substituted 3-hydroxy azetidin-2-ones. Structural confirmation was achieved by 1H NMR, 13C NMR, HRMS, and stereochemical elucidation based on the J-coupling values of C3–H and C4–H. Among the series, compound 9j exhibited the most potent antibacterial activity against MRSA (MIC: 7.5 μg/mL), outperforming Tetracycline. Mechanistic investigation using ROS quantification (DCFH-DA assay) revealed markedly elevated intracellular ROS (OD: 71,467), suggesting a possible ROS-mediated bacterial damage mechanism. Molecular docking interactions further supported the strong binding of 9j to penicillin-binding protein 2a (PBP2a, PDB: 1VQQ) with a docking score of –6.68 kcal/mol. Additionally, 9j exhibited selective cytotoxicity toward HCT-116 colon cancer cells with an IC50 value of 9.82 ± 0.21 μM while maintaining moderate viability (~52%) in NIH-3T3 normal fibroblast cells. Collectively, these findings highlight phenylvinylsulfonate-anchored azetidin-2-ones as promising antibacterial agents with a ROS-driven mechanism and supplementary selective cytotoxic potential.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659550","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

Solvent and Catalyst-Free One-Pot Synthesis of Tetrahydropyrimidine Analogs for Their Larvicidal Activity and Structural Insights 无溶剂和无催化剂一锅法合成四氢嘧啶类似物的杀幼虫活性及其结构研究

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-12-04 DOI: 10.1002/ardp.70162

Keshab M. Bairagi, Sandeep Chandrashekharappa, Jyoti Swarup Thakur, Rahul D. Nagdeve, Rohit Bhowal, Manasmita Panda, Deepak Chopra, Raquel M. Gleiser, Abdulaziz Saleh Almulhim, Osama I. Alwassil, Katharigatta N. Venugopala, Viresh Mohanlall, Susanta K. Nayak

{"title":"Solvent and Catalyst-Free One-Pot Synthesis of Tetrahydropyrimidine Analogs for Their Larvicidal Activity and Structural Insights","authors":"Keshab M. Bairagi, Sandeep Chandrashekharappa, Jyoti Swarup Thakur, Rahul D. Nagdeve, Rohit Bhowal, Manasmita Panda, Deepak Chopra, Raquel M. Gleiser, Abdulaziz Saleh Almulhim, Osama I. Alwassil, Katharigatta N. Venugopala, Viresh Mohanlall, Susanta K. Nayak","doi":"10.1002/ardp.70162","DOIUrl":"https://doi.org/10.1002/ardp.70162","url":null,"abstract":"<div>\u0000 \u0000 A series of ester derivatives of (6-methyl-4-phenyl-2-thioxo-1, 2, 3, 4-tetrahydropyrimidin-5-yl)(piperidin-1-yl) methanone (6a–6k) have been synthesized using a solvent and catalyst-free one-pot two-step synthetic method. These 11 molecules have been characterized by spectroscopic techniques such as FT-IR, NMR (1H and 13C), and single-crystal x-ray structural analysis. The Hirshfeld surface and 2D fingerprint plot elucidated the intermolecular interactions and their contribution to crystal packing. Furthermore, the computational calculations, such as FMOs and MEP, revealed the global reactivity descriptors and sites for noncovalent interactions, such as hydrogen bonding, respectively, in these pharmacophores. Among these derivatives, the 6h molecule, which bears –CF3 on the phenyl ring, has piperidine substitution on the ester group and contains a thiourea moiety, demonstrated the best larvicidal activity against Anopheles arabiensis, achieving a 94% mortality rate compared to the standard sample Temephos (98%).</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659551","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

New Se-Compounds With Antileishmanial, Antitumor, and Carbonic Anhydrase Inhibitory Properties 具有抗利什曼原虫、抗肿瘤和碳酸酐酶抑制特性的新硒化合物

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-12-03 DOI: 10.1002/ardp.70145

Cristina Morán-Serradilla, Daniel Plano, Andrea Angelli, Arun K. Sharma, Carmen Sanmartin, Claudiu T. Supuran

{"title":"New Se-Compounds With Antileishmanial, Antitumor, and Carbonic Anhydrase Inhibitory Properties","authors":"Cristina Morán-Serradilla, Daniel Plano, Andrea Angelli, Arun K. Sharma, Carmen Sanmartin, Claudiu T. Supuran","doi":"10.1002/ardp.70145","DOIUrl":"https://doi.org/10.1002/ardp.70145","url":null,"abstract":"In the pursuit of novel agents for treating leishmaniasis and cancer, we have synthesized a small library of phenylcarboxamide-selenium analogs and evaluated their in vitro antileishmanial, anticancer, and carbonic anhydrase inhibitory activities. The two trifluoromethoxy-substituted aniline derivatives (3 and 6) exhibited IC50 values in the low micromolar range in both Leishmania major and Leishmania infantum promastigotes and presented better selectivity indexes (SIs) than the reference drugs (miltefosine and paromomycin). Furthermore, all of the reported compounds displayed an outstanding antitumoral activity against a panel of 60 cancer cell lines of the National Cancer Institute's (NCI) Developmental Therapeutic Program (DTP). The cytotoxicity of compounds 1–3 in nonmalignant HaCaT cells was also evaluated. Furthermore, as several selenocompounds have previously been proven to inhibit tumor-associated human carbonic anhydrase (hCA) isoforms, all the compounds were assessed against hCA I, II, IX, and XII. Derivative 6 stood out as it inhibited tumor-associated isoform XII and the cytosolic hCA II isoform in the low micromolar range.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659459","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

Issue Information: Arch Pharm (12/2025) 发行资料：Arch Pharm （12/2025）

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-12-03 DOI: 10.1002/ardp.70167

引用次数: 0

Recent Advances in the Biological Activities of Monocarbonyl Curcumin Analogues (MACs) 单羰基姜黄素类似物（MACs）生物活性研究进展

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-12-03 DOI: 10.1002/ardp.70164

Amol A. Nagargoje, Sharad P. Panchgalle, Madiha M. Siddiqui, Mubarak H. Shaikh, D. More Dipti, Bapurao B. Shingate

引用次数: 0

Design, Synthesis, and Selective Antiproliferative Activity of Indolizine Derivatives as Microtubule Destabilizers 吲哚嗪衍生物作为微管不稳定剂的设计、合成和选择性抗增殖活性

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-12-03 DOI: 10.1002/ardp.70161

Victor Hugo Catricala Fernandes, Maitê Bueno Giometti, Franco Jazon Caires, Gabriel de Paula Bueno, Gabriel da Silva, Andréia Machado Leopoldino, Anna Junker, Giuliano Cesar Clososki

{"title":"Design, Synthesis, and Selective Antiproliferative Activity of Indolizine Derivatives as Microtubule Destabilizers","authors":"Victor Hugo Catricala Fernandes, Maitê Bueno Giometti, Franco Jazon Caires, Gabriel de Paula Bueno, Gabriel da Silva, Andréia Machado Leopoldino, Anna Junker, Giuliano Cesar Clososki","doi":"10.1002/ardp.70161","DOIUrl":"https://doi.org/10.1002/ardp.70161","url":null,"abstract":"The development of selective anticancer agents with minimal off-target toxicity remains a major therapeutic goal. In this study, we synthesized and evaluated a series of 32 indolizine derivatives for antiproliferative activity against oral (CAL-27), breast (BT-20), and gastric (HGC-27) cancer cell lines, as well as non-tumoral fibroblasts (OHMF). Compounds 8e and 8h emerged as potent and selective candidates, exhibiting nanomolar IC₅₀ values (47–117 nM) and negligible cytotoxicity toward healthy cells. These compounds induced G2/M cell-cycle arrest, inhibited tubulin polymerization, and modulated proteins related to apoptosis and proliferation, including p-AKT, cyclin D1, Bcl-2, and p21. Docking studies confirmed their interaction with the colchicine-binding site of tubulin. Together, the results support further investigation of these compounds as microtubule-interacting agents with selective antiproliferative activity.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659460","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

Exploring Nirmatrelvir Derivatives Through P2 Substituent Modifications and Warhead Innovations Targeting the Main Protease of SARS-CoV-2 通过P2取代基修饰和弹头创新探索针对SARS-CoV-2主要蛋白酶的Nirmatrelvir衍生物

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-11-29 DOI: 10.1002/ardp.70158

Felipe Cardoso Prado Martins, Johannes Lang, Fernanda dos Reis Rocho, Xianxian Wang, Vinícius Bonatto, Jerônimo Lameira, Christian Klein, Carlos Alberto Montanari

{"title":"Exploring Nirmatrelvir Derivatives Through P2 Substituent Modifications and Warhead Innovations Targeting the Main Protease of SARS-CoV-2","authors":"Felipe Cardoso Prado Martins, Johannes Lang, Fernanda dos Reis Rocho, Xianxian Wang, Vinícius Bonatto, Jerônimo Lameira, Christian Klein, Carlos Alberto Montanari","doi":"10.1002/ardp.70158","DOIUrl":"https://doi.org/10.1002/ardp.70158","url":null,"abstract":"The COVID-19 pandemic underscored the urgent need for effective antiviral agents, particularly against coronaviruses, which pose a continuing threat of future outbreaks. Targeting the main protease (Mpro), a key enzyme in viral replication, represents a promising therapeutic strategy. This study investigates structural modifications to known Mpro inhibitors, focusing on substitutions at the P2 position to explore alterations in both inhibitory potency and metabolic stability. Computational modeling and biochemical assays revealed that incorporating large, hydrophobic, and π-rich groups, such as the 4-phenylproline, significantly enhances binding affinity. Additionally, we evaluated warheads that have not yet been explored in the context of SARS-CoV-2 Mpro inhibition. Among these, fluoro-vinylsulfone and nitrile groups demonstrated superior inhibitory activity. A fragment-merging strategy combining an optimized P2 substituent with the nitrile warhead yielded a hybrid molecule with binding affinity comparable to nirmatrelvir. However, other analogs incorporating individual warhead optimizations displayed similar potency. These findings generate valuable insights into the design of robust Mpro inhibitors and support their potential development as broad-spectrum antiviral agents.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619285","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

C-5-Arylidene-Thiazolidine-2,4-Dione Analogs Against Aldose Reductase: Design, Synthesis, Biological Evaluation, and Computational Insights 抗醛糖还原酶的c -5-芳基烷-噻唑烷-2,4-二酮类似物：设计、合成、生物学评价和计算见解

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-11-29 DOI: 10.1002/ardp.70159

Rajiv Patel, Sanjeev Ranjan, Nandini, Anwesha Das, Arijit Nandi, Sant Kumar Verma

{"title":"C-5-Arylidene-Thiazolidine-2,4-Dione Analogs Against Aldose Reductase: Design, Synthesis, Biological Evaluation, and Computational Insights","authors":"Rajiv Patel, Sanjeev Ranjan,  Nandini, Anwesha Das, Arijit Nandi, Sant Kumar Verma","doi":"10.1002/ardp.70159","DOIUrl":"https://doi.org/10.1002/ardp.70159","url":null,"abstract":"<div>\u0000 \u0000 Diabetic complications are major health problems that happen to people with diabetes when their blood sugar levels stay high for a long time and damage various body organs and systems. Inhibition of aldose reductase has emerged as a promising strategy for drug development and the management of diabetes-associated complications. In the research article, a novel series of 12 compounds, “C−5-arylidene thiazolidine-2,4-dione derivatives” was constructed, synthesized, and characterized using both spectral and non-spectral techniques. The confirmed synthesized compounds were subsequently screened for in vitro aldose reductase inhibitory activity. Among them, compounds 9h and 9a exhibited superior potency against aldose reductase protein with IC50 values of 0.98 and 1.05 µM, respectively, as compared with the reference drug epalrestat (IC50 value of 1.20 µM). Additionally, compounds 9l and 9i showed moderate aldose reductase inhibitory activity with an IC50 value of 1.36 and 2.47 µM, respectively. Furthermore, the top four best active compounds were selected for in vivo anti-hyperglycaemic activity. Results revealed that all the tested compounds significantly decreased blood glucose levels at all time intervals. Computational analysis revealed that all synthesized candidates bound firmly in the protein cavity of aldose reductase via hydrogen bonds and steric interaction with the range of docking score −10.21 to −11.81 kcal/mol. Predicted in silico toxicity data suggested that the synthesized compounds were inactive and nontoxic against peroxisome proliferator-activated receptor-γ protein. These finding results support the potential of thiazolidine-2,4-dione derivatives as promising AR inhibitors for managing diabetic complications.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618930","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