Archiv der Pharmazie最新文献_第2页

Synthesis and Antichlamydial Activity of Novel Benzylaminophenazines Against Chlamydia trachomatis 新型苯氨基吩嗪的合成及其对沙眼衣原体的抗衣原体活性。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-10-07 DOI: 10.1002/ardp.70351

Yunfeng Ge, Wen Zhang, Wenjing Sang, Xinyang Sun, Shengming Ding, Yu Zhao, Xiaofeng Bao

{"title":"Synthesis and Antichlamydial Activity of Novel Benzylaminophenazines Against Chlamydia trachomatis","authors":"Yunfeng Ge, Wen Zhang, Wenjing Sang, Xinyang Sun, Shengming Ding, Yu Zhao, Xiaofeng Bao","doi":"10.1002/ardp.70351","DOIUrl":"10.1002/ardp.70351","url":null,"abstract":"<div>\u0000 \u0000 A series of phenazine derivatives with C-3 or C-4 benzylamino substituents were synthesized via Buchwald–Hartwig amination and evaluated for antichlamydial activity against Chlamydia trachomatis serovars L2 and D. All compounds exhibited micromolar inhibitory activity, with compound 7d showing the most potent effect (IC50 < 1 μM) but significant host cell cytotoxicity. In contrast, compounds 5g and 7c demonstrated favorable selectivity, with potent antichlamydial activity and no cytotoxicity at 16 μM. Mechanistic studies revealed that 5g and 7c inhibit Chlamydia through a dual mechanism: they block the initial stage of infection by targeting host cells, and they also interfere with later stages of intracellular reticulate body (RB) development. This represents the first report of phenazine derivatives acting via host cell targeting rather than direct action on elementary bodies (EBs). Structure–activity relationship analyses indicated that the electronic nature and chain length of substituents significantly influence both activity and cytotoxicity. Collectively, these findings identify 5g and 7c as promising lead compounds for the development of novel antichlamydial agents with a unique mechanism of action.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126333","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

Synergistic Cytotoxicity of Cafestol and Kahweol With Doxorubicin in Breast Cancer Cells Involves TNF‑α Targeting and NF‑κB Downregulation 咖啡醇和咖啡醇与阿霉素对乳腺癌细胞的协同细胞毒性作用涉及TNF - α靶向和NF - κB下调。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-10-07 DOI: 10.1002/ardp.70359

Layane D. Souza, Fábio Junior M. Novaes, Carlos Luan A. Passos, Ísis S. S. de Amorim, Pedro Nicolau-Neto, Juliana A. Rodrigues, Adilson F. Teixeira, Christian Ferreira, Nathalia Alexia N. dos Santos, Priscila G. Camargo, Marcelle L. F. Bispo, Camilo Henrique S. Lima, Bruno Ricardo B. Pires, Adenilson de Sousa da Fonseca, Claudia M. Rezende, Eliane Fialho, Andre Luiz Mencalha

{"title":"Synergistic Cytotoxicity of Cafestol and Kahweol With Doxorubicin in Breast Cancer Cells Involves TNF‑α Targeting and NF‑κB Downregulation","authors":"Layane D. Souza, Fábio Junior M. Novaes, Carlos Luan A. Passos, Ísis S. S. de Amorim, Pedro Nicolau-Neto, Juliana A. Rodrigues, Adilson F. Teixeira, Christian Ferreira, Nathalia Alexia N. dos Santos, Priscila G. Camargo, Marcelle L. F. Bispo, Camilo Henrique S. Lima, Bruno Ricardo B. Pires, Adenilson de Sousa da Fonseca, Claudia M. Rezende, Eliane Fialho, Andre Luiz Mencalha","doi":"10.1002/ardp.70359","DOIUrl":"10.1002/ardp.70359","url":null,"abstract":"Breast cancer (BC) is the most common cancer in women worldwide. Natural compounds have been studied to improve chemotherapy efficiency. Cafestol and kahweol (C&K) are diterpenes from coffee lipid fraction, with potential anticancer activity, whose effects and association with chemotherapeutic drug doxorubicin in BC cells are still unknown. Here, we evaluated the synergistic cytotoxic effects of the C&K with doxorubicin and their molecular mechanisms in BC cells. Cell viability was assessed by the MTT assay. Flow cytometry was used to analyze apoptosis, cell cycle, and NF-κB levels. The microarray assay was performed to identify altered signaling pathways, and molecular docking was utilized to predict the interaction between C&K and TNF-α. In addition, TCGA data were explored to evaluate the clinical association between the expression of C&K-regulated genes and TNF-α/NF-κB pathway genes. C&K was cytotoxic and increased the doxorubicin cytotoxicity, augmented the sub-G0/G1 phase, downregulated TNF-α/NF-κB pathway, decreased NF-κB protein levels, and showed affinity for TNF-α by molecular docking. Moreover, considering the C&K-modulated genes, BLOC1S1 acted as a protective factor for BC, and these genes were negatively correlated with TNF-α/NF-κB genes. Our data suggest that C&K have cytotoxic properties by inhibiting TNF-α/NF-κB pathway and interacting synergistically with doxorubicin in BC cells.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70359","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126236","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

Trends in Developing PPAR-Gamma and FFAR1/GPCR40 Modulators for Managing Type-II Diabetes Mellitus PPAR-Gamma和FFAR1/GPCR40调节剂治疗ii型糖尿病的发展趋势

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-10-05 DOI: 10.1002/ardp.70335

Ahmad J. Almalki

{"title":"Trends in Developing PPAR-Gamma and FFAR1/GPCR40 Modulators for Managing Type-II Diabetes Mellitus","authors":"Ahmad J. Almalki","doi":"10.1002/ardp.70335","DOIUrl":"10.1002/ardp.70335","url":null,"abstract":"<div>\u0000 \u0000 Agonists of peroxisome proliferator-activated receptor-gamma (PPAR-γ) gained the main interest for managing type-II diabetes mellitus (T2DM) as insulin sensitizers. Serving as 2nd-line therapeutics, glitazones were the first class, influencing PPAR-γ, yet a range of adverse effects were reported regarding the use of PPAR-γ full agonists. Agents having partial PPAR-γ agonistic effect or selectively modulate PPAR-γ transactivity have been introduced. Nonetheless, most of these agents were abandoned at phase II clinical trials for unbalanced supra-therapeutic activation of the multireceptors. Despite clinical attentions towards advers effects, these clinical failures have defined the pharmacological boundaries for safer drug design. The emerging clinical pathway focuses on bifunctional hybridization to achieve glucose homeostasis through synergistic modulation rather than high-dose single-target activation. It was not until 2003 where G-protein-coupled receptor 40 (GPCR40), currently named as free fatty acid receptor-I (FFAR1), was discovered. A plausible FFAR1/PPAR-γ crosstalk has been suggested linking both receptors and insulin secretion. These findings triggered the development of several FFAR1 agonists. Nevertheless, and till the time of writing this review, limited studies proposed the synthesis of such hybrid molecules with only one reaching a regional market. The provided review deals with recent advances of both FFAR1 and PPAR-γ ligands in managing T2DM. Up-to-date medicinal chemistry description of FFAR1 and PPAR-γ modulators as well as each dual agonists have been provided with highlighted structural diversity and activity interlink for each main class.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101611","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

Intrinsic Reactivity of Sulfonyl Imidazole and Triazole Electrophiles for Covalent Probe Design 磺胺基咪唑和三唑类亲电试剂的共价探针设计。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-10-04 DOI: 10.1002/ardp.70353

Paramita Pal, Hannah Unsworth, Lyn H. Jones

{"title":"Intrinsic Reactivity of Sulfonyl Imidazole and Triazole Electrophiles for Covalent Probe Design","authors":"Paramita Pal, Hannah Unsworth, Lyn H. Jones","doi":"10.1002/ardp.70353","DOIUrl":"10.1002/ardp.70353","url":null,"abstract":"<div>\u0000 \u0000 Sulfonyl exchange electrophiles are increasingly used in covalent probe and drug discovery, yet their intrinsic reactivity and plasma stability remain poorly defined, limiting rational warhead selection. Here we establish a systematic LC-MS framework to quantify the reactivity of sulfonyl imidazole and triazole electrophiles across key biological nucleophiles together with matched plasma stability. Sulfonyl imidazoles display attenuated cysteine reactivity and markedly improved stability while retaining intrinsic tyrosine reactivity, whereas sulfonyl triazoles exhibit high electrophilicity and rapid degradation. These data reveal clear relationships between aryl electronics, leaving group ability, nucleophile selectivity, and in vivo-relevant stability. To demonstrate practical utility, we applied a SuFEx-click transformation to convert the kinase-directed probe XO44 into a sulfonyl imidazole analogue, yielding a stable SuDEx probe (JL-51) that maintains the proteome-labeling profile of the parent reagent. The corresponding sulfonyl triazole congener was rapidly hydrolyzed. This work provides a mechanistic foundation and practical strategy for designing next-generation sulfonyl exchange covalent probes.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101487","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

Rational Design of N-2-(7-Chloroquinolin-4-ylamino)ethyl Amides Active Against Chloroquine-Resistant Plasmodium falciparum 抗氯喹耐药恶性疟原虫的N-2-（7-氯喹啉-4-氨基）乙基酰胺的合理设计

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-10-04 DOI: 10.1002/ardp.70350

Everton P. Silva, Camila S. Barbosa, Anna C. C. Aguiar, Ramon G. Oliveira, Thiago A. M. Brito, Marcelo F. R. Silva, Helivaldo D. S. Souza, Petrônio F. Athayde-Filho, Gabriela F. Fiss

{"title":"Rational Design of N-2-(7-Chloroquinolin-4-ylamino)ethyl Amides Active Against Chloroquine-Resistant Plasmodium falciparum","authors":"Everton P. Silva, Camila S. Barbosa, Anna C. C. Aguiar, Ramon G. Oliveira, Thiago A. M. Brito, Marcelo F. R. Silva, Helivaldo D. S. Souza, Petrônio F. Athayde-Filho, Gabriela F. Fiss","doi":"10.1002/ardp.70350","DOIUrl":"10.1002/ardp.70350","url":null,"abstract":"Motivated by the antimalarial potential demonstrated by benzamide derivatives of 4-alkylamino-7-chloroquinolines against chloroquine-resistant Plasmodium falciparum, we designed and synthesized a rational series of N-2-(7-chloroquinolin-4-ylamino)ethyl amides to investigate the effects of electron-withdrawing and donating substituents on antiplasmodial and cytotoxicity properties, from prediction to in vitro assays. From an initial screening of 22 chloroquine (CQ) analogs, 16 compounds with two distal amino groups in the alkyl linker showed IC50 values below 1000 nM against the CQ-sensitive 3D7 strain. Next, their activity against the CQ-resistant K1 strain, in silico toxicity, predicted using the pkCSM program, and in vitro cytotoxicity on HepG2 cells were evaluated. Benzamides containing electron-withdrawing chlorine and nitro groups showed the most promising profiles, with IC50 values against the CQ-resistant K1 strain (IC50K1, 55–72 nM) and resistance index (RI, 0.7–1.9) values outperforming CQ (IC50K1 = 141 nM, RI = 7.1). Although predicted to be hepatotoxic, these compounds were not cytotoxic to HepG2 cells at the tested concentrations, showing CC50 values above 12,500 nM and selectivity indices greater than 115. Compared with CQ, a 3D qualitative SAR model indicated that increased lipophilicity around the distal benzamide moiety enhances antiplasmodial activity against the K1 strain, contributing to the observed potency.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101417","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

Functionalized Benzisoxazoles: Recent Developments in Diversified Synthetic Strategies and Cytotoxic Potential 功能化苯并异恶唑：多样化合成策略和细胞毒性潜能的最新进展。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-10-04 DOI: 10.1002/ardp.70340

Shibangi Bhattacharjee, Nayanita Chakraborty, Rajesh Tiwari, Kamya Goyal, Vikramdeep Monga

{"title":"Functionalized Benzisoxazoles: Recent Developments in Diversified Synthetic Strategies and Cytotoxic Potential","authors":"Shibangi Bhattacharjee, Nayanita Chakraborty, Rajesh Tiwari, Kamya Goyal, Vikramdeep Monga","doi":"10.1002/ardp.70340","DOIUrl":"10.1002/ardp.70340","url":null,"abstract":"<div>\u0000 \u0000 Benzisoxazoles are pivotal heterocyclic scaffolds that have emerged as focal points in both synthetic and medicinal chemistry due to their broad synthetic applications and a wide spectrum of pharmacological properties. Their unique structural framework, along with the presence of an oxygen–nitrogen bond within a fused bicyclic ring system, confers remarkable physicochemical and biological properties, including anticancer, antibacterial, antifungal, antiviral, anti-inflammatory and diuretic activities. Appropriately constructed benzisoxazole scaffolds display remarkable potential to interact with a broad range of biological targets, thereby offering significant opportunities for the development of novel therapeutic agents with diverse mechanisms of action. Chemists have been intrigued by the fascinating properties of benzisoxazoles, and extensive scientific studies have been carried out to integrate the benzisoxazole scaffold into various bioactive compounds, including complex molecular frameworks. The past few years have witnessed tremendous progress in the development of various multicomponent one-pot synthetic strategies, including transition-metal catalysis, metal-free cyclization and microwave-assisted synthesis for diversely substituted benzisoxazole derivatives. This review highlights recent advancements in the synthetic chemistry of functionalized benzisoxazoles, including marketed drugs and agents in clinical trials. Furthermore, recent developments in the medicinal chemistry of benzisoxazole derivatives as anticancer agents, encompassing their mechanistic aspects, structure-activity relationships, and in silico studies, have been compiled. Drawing on the literature, the authors aim to provide a broad perspective and valuable insights for researchers, thereby inspiring and accelerating the development of novel benzisoxazole-appended anticancer therapeutics with significant biological implications.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101430","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

Pyridine and Fused Pyridine Derivatives as Selective COX-2 Inhibitors: A Comprehensive Review of Synthetic Pathways, Anti-Inflammatory, and Antinociceptive Activities 吡啶和吡啶衍生物作为选择性COX-2抑制剂：合成途径、抗炎和抗伤害活性的综合综述。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-10-04 DOI: 10.1002/ardp.70349

Nada Reda, Eman M. Ahmed, Khaled O. Mohamed, Amira A. Helwa, Marwa S. A. Hassan

{"title":"Pyridine and Fused Pyridine Derivatives as Selective COX-2 Inhibitors: A Comprehensive Review of Synthetic Pathways, Anti-Inflammatory, and Antinociceptive Activities","authors":"Nada Reda, Eman M. Ahmed, Khaled O. Mohamed, Amira A. Helwa, Marwa S. A. Hassan","doi":"10.1002/ardp.70349","DOIUrl":"10.1002/ardp.70349","url":null,"abstract":"<div>\u0000 \u0000 Selective cyclooxygenase-2 inhibitors (COXIBs) are preferred over traditional nonsteroidal anti-inflammatory drugs (NSAIDs) owing to their improved gastrointestinal and renal safety profile. Pyridine is one of the most important nitrogen-containing heterocyclic scaffolds, and it is present in the structures of more than 7000 marketed drugs and biologically active compounds. Among these are anti-inflammatory agents, including the selective cyclooxygenase-2 (COX-2) inhibitors niflumic acid and etoricoxib. This review highlights the synthetic approaches to pyridine and fused pyridine derivatives, covering 42 published studies on pyridine synthesis, and critically evaluates 40 published studies on pyridine-containing scaffolds exhibiting COX-2 inhibitory activity. Several pyridine derivatives demonstrated potent COX-2 inhibitory activity, with reported IC50 values ranging from the nanomolar to micromolar level. Analysis of these studies revealed that 17 of the 40 studies reported compounds that exhibited superior COX-2 inhibitory activity than the reference drugs evaluated under the same experimental conditions. Among these 17 studies, 6 involved fused pyridine scaffolds. These findings support the pyridine scaffold as a promising platform for the development of selective COX-2 inhibitors. Therefore, this review provides a valuable resource for guiding the rational design and development of novel selective COX-2 inhibitors.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101454","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

Simvastatin Mitigates Chemotherapy-Induced Depressive-Like Behaviors in Rats 辛伐他汀减轻大鼠化疗诱导的抑郁样行为。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-10-04 DOI: 10.1002/ardp.70332

Heba A. Elbadawy, Marwa A. Ali, Eman Badr, Shaimaa G. Gahin, Reem N. El-Naga, Mai F. Tolba

{"title":"Simvastatin Mitigates Chemotherapy-Induced Depressive-Like Behaviors in Rats","authors":"Heba A. Elbadawy, Marwa A. Ali, Eman Badr, Shaimaa G. Gahin, Reem N. El-Naga, Mai F. Tolba","doi":"10.1002/ardp.70332","DOIUrl":"10.1002/ardp.70332","url":null,"abstract":"<div>\u0000 \u0000 Beyond its primary lipid-lowering efficacy, simvastatin (SIM) demonstrates neuroprotective potential mediated by its antioxidant, anti-apoptotic, and anti-inflammatory bioactivities. Consequently, the current study tested the hypothesis that SIM confers neuroprotection in a rodent model of depressive-like phenotypes induced by Doxorubicin (DOX)/Cyclophosphamide (CP) polychemotherapy. Rats were divided into four cohorts (n = 10 per group). Control; SIM-alone; chemotherapy; SIM/chemotherapy combination. SIM co-treatment significantly improved depression-like phenotypes throughout the forced swim test, the sucrose splash test as well as the open field test. This is in addition to alleviating hippocampal neuro-inflammation and oxidative stress vs the chemotherapy-combination group. Concurrently, SIM reduced hippocampal oxidative stress (51% decrease in MDA) and inflammation (70% and 42% decrease in TNF-α and NF-κB). SIM also attenuated apoptosis (29% reduction in active caspase-3). Pathway enrichment (PEA) and Gene Ontology (GO) analyses supported that SIM's cytoprotective effects may be mediated through multiple pathways, including lipid metabolism, immunity, and apoptosis regulation. In conclusion, SIM co-administration effectively attenuated the molecular alterations elicited by the DOX/CP combination within the hippocampal tissues. Collectively, these data position SIM as a promising candidate for mitigating chemotherapy-associated depression. Nevertheless, further investigation is warranted to fully elucidate the underlying antidepressant mechanisms of statins and to validate their clinical efficacy.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101470","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

Dual DHFR and DNA Gyrase Inhibitory Potency of Some Novel Pyridine Hybrids Linked to Pyrazolo[1,5-a]Pyrimidine Units: Antibacterial Screening and SAR Study 与吡唑啉[1,5-a]嘧啶单位连接的新型吡啶杂种的双DHFR和DNA旋切酶抑制效能：抗菌筛选和SAR研究。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-10-04 DOI: 10.1002/ardp.70352

Ahmed A. M. Ahmed, Ahmed E. M. Mekky, Ahmed H. Alanazi, Sultan A. Alsahli, Sherif M. H. Sanad

{"title":"Dual DHFR and DNA Gyrase Inhibitory Potency of Some Novel Pyridine Hybrids Linked to Pyrazolo[1,5-a]Pyrimidine Units: Antibacterial Screening and SAR Study","authors":"Ahmed A. M. Ahmed, Ahmed E. M. Mekky, Ahmed H. Alanazi, Sultan A. Alsahli, Sherif M. H. Sanad","doi":"10.1002/ardp.70352","DOIUrl":"10.1002/ardp.70352","url":null,"abstract":"<div>\u0000 \u0000 Bacterial infections are significant issues that endanger public health and deplete financial resources. A potential strategy to combat these infections is molecular hybridization, which combines pharmacophores from potential drugs to produce hybrid scaffolds that are more effective. The preparation of pyridines attached to pyrazolopyrimidine units with promising antimicrobial potency and dual inhibitory capacity against DNA gyrase and dihydrofolate reductase (DHFR) is the aim of this work. A green procedure was conducted by reacting the suitable 2-cyanoacetamides with aromatic aldehydes and malononitrile in refluxing ethanol for 5–8 h containing choline hydroxide to give pyrazolopyrimidine-linked 4-arylpyridine-3,5-dicarbonitrile hybrids 1 and 2 in 74%–94% yields. In general, 5,7-diphenylpyrazolopyrimidine-linked pyridines 2 showed slightly more increased antibacterial activity, particularly against methicillin-resistant Staphylococcus aureus (MRSA), compared to 5,7-dimethylpyrazolopyrimidine-linked pyridines 1. The presence of para-substituted arene units at pyridine-C4 connected to electron-withdrawing groups resulted in increased efficacy. Pyridines 1d and 2d, attached to 4-nitrophenyl groups, showed good potency with MIC/MBC of 2.52/5.04 and 2.03/4.07 µM against S. aureus and Escherichia coli, and with MIC/MBC of 5.04/20.17 and 4.07/16.26 µM against MRSA. 1d and 2d showed promising potency with IC50 of 3.296 and 3.002 μM against S. aureus DNA gyrase, IC50 of 3.702 and 3.304 μM against E. coli DNA gyrase, and IC50 of 0.171 and 0.162 µM against E. coli DHFR.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101421","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

1,2,3-Triazole-Indole Derived Hybrids: Recent Progress and Therapeutic Perspectives for Cancer Treatment. 1,2,3-三唑-吲哚衍生物：癌症治疗的最新进展和治疗前景。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-10-01 DOI: 10.1002/ardp.70363

Jialin Zhou, Zhi Xu

{"title":"1,2,3-Triazole-Indole Derived Hybrids: Recent Progress and Therapeutic Perspectives for Cancer Treatment.","authors":"Jialin Zhou, Zhi Xu","doi":"10.1002/ardp.70363","DOIUrl":"https://doi.org/10.1002/ardp.70363","url":null,"abstract":"1,2,3-Triazole and indole-derived scaffolds are privileged nitrogen-containing heterocyclic pharmacophores that form abundant non-covalent interactions with tumor-related biomacromolecules. Molecular hybridization that integrates these two scaffolds into a single molecular scaffold yields 1,2,3-triazole-indole-derived hybrids, which can mitigate intrinsic drawbacks of single-heterocycle anticancer small-molecule agents, such as insufficient target selectivity, unsatisfactory pharmacokinetic performance, and acquired multidrug resistance. This review summarizes research advances on 1,2,3-triazole-indole-derived anticancer hybrids published from 2021 to the present, and the structure-activity relationships (SARs) as well as modes of action are discussed. These hybrids exert broad-spectrum multi-target anticancer effects through kinase inhibition, cell-cycle arrest, caspase-dependent apoptosis, anti-angiogenic and anti-migratory activities, tubulin polymerization disruption, as well as modulation of autophagy, immunogenic cell death, and the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling axis. Representative candidates exhibit robust in vitro antiproliferative potency against diverse cancer cell lines, favorable selectivity toward normal human cells, satisfactory plasma metabolic stability, and potent in vivo tumor growth inhibitory effects. This comprehensive overview provides systematic theoretical guidance and rational design principles for further development and clinical translation of high-efficiency, low-toxicity 1,2,3-triazole-indole-derived hybrid lead compounds for precise therapy against cancers.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 10","pages":"e70363"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219639","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