Archiv der Pharmazie最新文献_第6页

Advances in Xanthine Oxidase Inhibition: A Review of Potential Bioactive Synthetic Compounds 黄嘌呤氧化酶抑制研究进展：潜在生物活性合成化合物综述

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-21 DOI: 10.1002/ardp.70079

Giorgio Antoniolli, Gabriel Rodrigues de Moraes, Rafael Porreca Neves da Costa, Giovani Augusto Rosendo de Campos, Fernando Coelho

{"title":"Advances in Xanthine Oxidase Inhibition: A Review of Potential Bioactive Synthetic Compounds","authors":"Giorgio Antoniolli, Gabriel Rodrigues de Moraes, Rafael Porreca Neves da Costa, Giovani Augusto Rosendo de Campos, Fernando Coelho","doi":"10.1002/ardp.70079","DOIUrl":"https://doi.org/10.1002/ardp.70079","url":null,"abstract":"Hyperuricemia and gout are conditions that continue to present significant therapeutic challenges, mainly due to limitations of current treatments which may cause adverse effects such as hypersensitivity, hepatotoxicity, and cardiovascular risks. Additionally, the development of new drugs faces obstacles including toxicity, low bioavailability, and potential drug interactions. In this context, the search for new synthetic xanthine oxidase inhibitors is essential to improve treatment efficacy, selectivity, and safety. New molecules can not only prolong the duration of therapeutic effects but also minimize adverse reactions. Moreover, several compounds under investigation exhibit additional pharmacological activities, such as anti-inflammatory, antioxidant, anticholinesterase, and anticancer properties. Recent research trends also include the use of artificial intelligence, computational modeling, and the exploration of natural products—such as flavonoids and alkaloids—as sources of inspiration for new synthetic inhibitors. Furthermore, strategies like combination therapies are being explored to enhance uric acid excretion. This review conducted a systematic search for new xanthine oxidase inhibitors (2025–2020), focusing on high-impact publications and organizing the compounds according to their molecular scaffolds (number of rings). This review highlights recent advances in the development of synthetic xanthine oxidase inhibitors, emphasizing their structural diversity and the continuous relevance of this study area. The discovery of new drug candidates has the potential to provide more effective and safer therapeutic options for patients in the near future.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881129","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

Exploration of New Dihydroindazole Derivatives as Promising Anti-TB Agents: Design, Synthesis, In Silico, and Biological Evaluation 新型抗结核药物双氢茚唑衍生物的探索：设计、合成、硅合成和生物学评价

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-15 DOI: 10.1002/ardp.70074

Pardeep Kumar, Pradip Malik, Juned Ali, Deepanshi Saxena, Anuradha Singampalli, Bandela Rani, Sri Mounika Bellapukonda, Ankita Devi, Nagesh A. Bhale, Amol G. Dikundwar, Srinivas Nanduri, Arunava Dasgupta, Sidharth Chopra, Yaddanapudi Venkata Madhavi

{"title":"Exploration of New Dihydroindazole Derivatives as Promising Anti-TB Agents: Design, Synthesis, In Silico, and Biological Evaluation","authors":"Pardeep Kumar, Pradip Malik, Juned Ali, Deepanshi Saxena, Anuradha Singampalli, Bandela Rani, Sri Mounika Bellapukonda, Ankita Devi, Nagesh A. Bhale, Amol G. Dikundwar, Srinivas Nanduri, Arunava Dasgupta, Sidharth Chopra, Yaddanapudi Venkata Madhavi","doi":"10.1002/ardp.70074","DOIUrl":"https://doi.org/10.1002/ardp.70074","url":null,"abstract":"<div>\u0000 \u0000 The escalating threat of drug-resistant Mycobacterium tuberculosis (Mtb) necessitates the discovery of novel chemotherapeutic agents. In this study, a series of dihydroindazole-based derivatives were designed, synthesized, and evaluated for their antimycobacterial potential. Among the synthesized compounds, 8u exhibited the most potent in vitro activity against Mtb H37Rv with a minimum inhibitory concentration (MIC) of 2 µg/mL, while 8i and 8q showed moderate activity (MIC = 8 µg/mL). Several analogs demonstrated MICs in the range of 16–32 µg/mL. 8u also displayed enhanced activity against single-drug-resistant Mtb strains, outperforming ethambutol and rifampicin. Structure–activity relationship analysis indicated that both the hydrazide linker and heteroaryl substitutions significantly influenced antimycobacterial activity. 8u was non-cytotoxic to Vero cells (CC₅₀ > 100 µg/mL), yielding a selectivity index (SI) > 50. Time–kill kinetics confirmed its bactericidal nature. Mechanistic investigations using molecular docking and 100-ns molecular dynamics simulations identified InhA as the probable molecular target. In silico ADMET predictions (QikProp and ProTox-3.0) supported favorable pharmacokinetic and toxicity profiles. Collectively, these findings highlight 8u as a promising lead for the development of next-generation anti-TB agents.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853776","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 and Antidiabetic Activity of Novel Pyrrole-3-Carboximidamide Derivatives as Dipeptidyl Peptidase-4 Inhibitors 新型二肽基肽酶-4抑制剂吡咯-3- carboximidamide衍生物的设计、合成及降糖活性研究

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-15 DOI: 10.1002/ardp.70077

Hossein Fasihi Dastjerdi, Nima Naderi, Amir Garmabdari, Manijeh Nematpour, Melika Ebrahimi, Samaneh Hosseinpoor, Fatemeh Saberinasab, Zahra Sheikholislam, Omid Hosseini, Elham Rezaee, Sayyed Abbas Tabatabai

{"title":"Design, Synthesis and Antidiabetic Activity of Novel Pyrrole-3-Carboximidamide Derivatives as Dipeptidyl Peptidase-4 Inhibitors","authors":"Hossein Fasihi Dastjerdi, Nima Naderi, Amir Garmabdari, Manijeh Nematpour, Melika Ebrahimi, Samaneh Hosseinpoor, Fatemeh Saberinasab, Zahra Sheikholislam, Omid Hosseini, Elham Rezaee, Sayyed Abbas Tabatabai","doi":"10.1002/ardp.70077","DOIUrl":"https://doi.org/10.1002/ardp.70077","url":null,"abstract":"<div>\u0000 \u0000 Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion, and dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as an effective therapeutic option. A new series of pyrrole-3-carboximidamide derivatives was designed, synthesized, and evaluated as DPP-4 inhibitors. Most of the synthesized compounds exhibited favorable inhibitory activity against the DPP-4 enzyme, and compounds 5f and 5g were found to be the most potent inhibitors with IC₅₀ values of 12.19 and 23.08 nM, respectively. In vivo studies in diabetic Wistar rats showed that daily administration of compound 5g for 2 weeks resulted in a significant decrease in blood glucose compared with the control group. Moreover, compound 5g was effective in reducing plasma glucose in an acute oral glucose tolerance test in NMRI mice. The antiglycemic effects of compound 5g were comparable with standard treatment by sitagliptin, with no effect on normoglycemic rats. Both the in vitro and in vivo antidiabetic properties suggest that compound 5g could be considered a promising candidate for development as an antidiabetic medication.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853777","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

Imidazolium-Based Lipid Analogs as Lipofection Reagents 咪唑类脂质类似物作为吸脂试剂

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-14 DOI: 10.1002/ardp.70076

Marco Pierau, Ronewa Nematswerani, Calvin Dunker, Frank Glorius, Anna Junker

{"title":"Imidazolium-Based Lipid Analogs as Lipofection Reagents","authors":"Marco Pierau, Ronewa Nematswerani, Calvin Dunker, Frank Glorius, Anna Junker","doi":"10.1002/ardp.70076","DOIUrl":"https://doi.org/10.1002/ardp.70076","url":null,"abstract":"Three imidazolium-based lipid analogs with varying degrees of saturation were synthesized and evaluated for their potential to enhance gene transfer in the 1321N1 and HEK-293FT cell lines. The analogs were incorporated into DPPC/DOPE-based liposomes and compared with two established transfection reagents, Lipofectamine3000 and FuGENE 4 K. Cytotoxicity assessments, as determined by lactate dehydrogenase assays, revealed a lower toxicity profile for the fully saturated compound 1 compared with its mono- (2) and di-unsaturated (3) counterparts. Notably, longer incubation times (24 h) amplified cytotoxic responses, with C17H31-IMeNMe3 (3) displaying the highest cell damage. Despite elevated toxicity relative to commercial reagents, compound 3 successfully delivered plasmid DNA using a PiggyBac transposon system, producing stable transfected cell lines after extended culture periods. C15H31-IMeNMe3 (1) achieved stable transfection but required longer colony expansion than the commercial controls, whereas C17H33-IMeNMe3 (2) did not yield transfected lines under the conditions tested. Overall, these results suggest that structural modifications, particularly the length of the alkyl chain and the number of double bonds, impact both cytotoxicity and transfection efficiency. The findings underscore the importance of rational lipid design, as stronger membrane interactions can enhance uptake while potentially heightening adverse effects. This study informs future development of safer, more effective nonviral delivery vectors.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832389","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

Novel Taurinamide-Based Compounds as Carbonic Anhydrase Inhibitors 新型牛磺酸胺类化合物作为碳酸酐酶抑制剂

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-13 DOI: 10.1002/ardp.70073

Ozlem Akgul, Gioele Renzi, Andrea Angeli, Marta Ferraroni, Fabrizio Carta, Claudiu T. Supuran

引用次数: 0

Design, Synthesis, and Biological Evaluation of Triazolopyrimidine–Isatin Hybrids as Promising Candidates for Triple-Negative Breast Cancer 三唑嘧啶- isatin杂合体作为三阴性乳腺癌有希望的候选物的设计、合成和生物学评价

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-13 DOI: 10.1002/ardp.70075

Shefali Chowdhary, Asif Raza, Natacha Henry, Pascal Roussel, Arun K. Sharma, Vipan Kumar

引用次数: 0

Design, Synthesis, and Molecular Evaluation of SNAr-Reactive N-(6-Fluoro-3-Nitropyridin-2-yl)Isoquinolin-3-Amines as Covalent USP7 Inhibitors Reveals an Unconventional Binding Mode snar反应性N-（6-氟-3-硝基吡啶-2-基）异喹啉-3-胺共价USP7抑制剂的设计、合成和分子评价揭示了一种非常规的结合模式

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-10 DOI: 10.1002/ardp.70053

Larissa N. Ernst, Jason Stahlecker, Finn Mier, Ricardo A. M. Serafim, Valentin R. Wydra, Benedikt Masberg, Simon J. Jaag, Cornelius Knappe, Michael Lämmerhofer, Thilo Stehle, Matthias Gehringer, Frank M. Boeckler

{"title":"Design, Synthesis, and Molecular Evaluation of SNAr-Reactive N-(6-Fluoro-3-Nitropyridin-2-yl)Isoquinolin-3-Amines as Covalent USP7 Inhibitors Reveals an Unconventional Binding Mode","authors":"Larissa N. Ernst, Jason Stahlecker, Finn Mier, Ricardo A. M. Serafim, Valentin R. Wydra, Benedikt Masberg, Simon J. Jaag, Cornelius Knappe, Michael Lämmerhofer, Thilo Stehle, Matthias Gehringer, Frank M. Boeckler","doi":"10.1002/ardp.70053","DOIUrl":"https://doi.org/10.1002/ardp.70053","url":null,"abstract":"The cysteine protease ubiquitin-specific protease 7 (USP7), also known as herpes-associated ubiquitin-specific protease (HAUSP), has gained increasing attention in recent years due to its proven overexpression in several cancer types and its role in tumorigenesis. Herein, after a design based on molecular docking experiments, we report the synthesis of a series of mildly electrophilic compounds that covalently modify the catalytic cysteine 223 in USP7 through a nucleophilic aromatic substitution (SNAr) reaction. The compounds were first evaluated using differential scanning fluorimetry (DSF) to describe their influence on the melting temperature of native and mutant USP7 variants. Furthermore, the possible formation of a covalent bond was analyzed using intact protein mass spectrometry (MS). For promising derivatives, IC50 values were determined in an enzyme activity assay to confirm an inhibitory effect on USP7. Finally, a co-crystal structure revealed that the prototype compound (7a) arylates the catalytic cysteine in the apo form of USP7 via an unconventional binding mode near the catalytic triad. The synthesis and biological evaluation of this compound series provides valuable structure–activity relationships (SAR) and reveals an interesting and unprecedented binding mode, thus providing a basis for improving USP7 inhibitors.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810973","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

One-Pot Synthesis of Novel 3-{(1H-Benzo[d]Imidazol-2-yl)Amino(Phenyl)Methyl}Benzofuran-2(3H)-Ones as Antimicrobial Agents and Their Molecular Docking Studies 新型抗菌药物3-{（1h -苯并[d]咪唑-2-基）氨基（苯基）甲基}苯并呋喃-2(3H)-的一锅合成及其分子对接研究

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-10 DOI: 10.1002/ardp.70069

Paras J. Patel, Mehul P. Parmar, Disha P. Vala, Kirti Antil, Subham G. Patel, Shana Balachandran, Divyang M. Patel, Nagesh Kumar Kandukuri, Madan Kumar Arumugam, Rakesh K. Sharma, Hitendra M. Patel

{"title":"One-Pot Synthesis of Novel 3-{(1H-Benzo[d]Imidazol-2-yl)Amino(Phenyl)Methyl}Benzofuran-2(3H)-Ones as Antimicrobial Agents and Their Molecular Docking Studies","authors":"Paras J. Patel, Mehul P. Parmar, Disha P. Vala, Kirti Antil, Subham G. Patel, Shana Balachandran, Divyang M. Patel, Nagesh Kumar Kandukuri, Madan Kumar Arumugam, Rakesh K. Sharma, Hitendra M. Patel","doi":"10.1002/ardp.70069","DOIUrl":"https://doi.org/10.1002/ardp.70069","url":null,"abstract":"<div>\u0000 \u0000 Aminobenzimidazole-coumaranone conjugates, specifically 3-{[(1H-benzo[d]imidazol-2-yl)amino](substitutedphenyl)methyl}benzofuran-2(3H)-ones, were synthesized through a one-pot reaction involving 2-coumaranone, aryl aldehydes, and 2-aminobenzimidazole. This reaction, catalyzed by triethylamine in acetonitrile at 80°C, achieved yields of up to 85%. Preparative liquid chromatography successfully isolated compounds 4b and 4c as two isomers with purities reaching 99.30%. Their absolute configurations, (S, R) for compound 4b and (R, S) for compound 4c, were determined using electronic circular dichroism and confirmed via TD-DFT calculations. The antimicrobial potential of the synthesized compounds (4a–j) and their enantiopure isomers (4b′, 4b″, 4c′, 4c″) was evaluated against the bacterial strains Bacillus subtilis, Staphylococcus aureus, Staphylococcus proteolyticus, and the fungal strains Candida albicans and Aspergillus niger. Notably, compounds 4a, 4d, 4i, and 4j exhibited superior antimicrobial activity. Molecular docking studies further reinforced these results, revealing strong receptor binding affinities (−7.5 to −10.5 kcal/mol), which surpass those of standard drugs. These findings highlight the promising potential of aminobenzimidazole-coumaranone conjugates as effective antimicrobial agents.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144807524","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

From Lab to Target: Pyrazole, Pyrazoline and Fused Pyrazole Derivatives as Receptor Tyrosine Kinase Inhibitors in Cancer Therapy 从实验室到靶点：吡唑、吡唑啉和融合吡唑衍生物作为受体酪氨酸激酶抑制剂在癌症治疗中的应用

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-10 DOI: 10.1002/ardp.70061

Michael M. Sawiris, Omneya M. Khalil, Peter A. Halim, Marwa S. A. Hassan

{"title":"From Lab to Target: Pyrazole, Pyrazoline and Fused Pyrazole Derivatives as Receptor Tyrosine Kinase Inhibitors in Cancer Therapy","authors":"Michael M. Sawiris, Omneya M. Khalil, Peter A. Halim, Marwa S. A. Hassan","doi":"10.1002/ardp.70061","DOIUrl":"https://doi.org/10.1002/ardp.70061","url":null,"abstract":"<div>\u0000 \u0000 Pyrazole derivatives have emerged as versatile scaffolds in the development of receptor tyrosine kinase inhibitors, offering promising avenues for targeted cancer therapy. Their therapeutic potential in cancer therapy is notable in many FDA-approved anticancer drugs. This review provides a comprehensive overview of the latest research from 2021 regarding novel pyrazole, pyrazoline, and fused pyrazole derivatives targeting receptor tyrosine kinases, namely: AXL, DDR, EGFR, FGFR, MET, CSF1R, RET, and VEGFR-2. This study focuses on the most active and promising candidates within each series of compounds. Key aspects covered include their cytotoxicity and enzyme inhibition results, with comparisons to reference drugs. The review also covers the molecular docking studies, highlighting critical binding interactions between the compounds and the protein kinase residues, and unveiling their molecular mechanisms of action. Structure–activity relationship analyses are also discussed, revealing the influence of structural modifications on biological activities. Furthermore, synthetic pathways for each series or key compounds are presented, offering a practical guide for researchers in the field. By integrating these elements, this review provides a solid foundation and rationale for the design, synthesis, and optimization of new pyrazole-based anticancer agents targeting receptor tyrosine kinases.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144807519","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

Nebivolol and Tadalafil Synergistically Ameliorate Insulin Resistance-Induced Retinopathy in Rats 奈比洛尔和他达拉非协同改善大鼠胰岛素抵抗性视网膜病变

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-10 DOI: 10.1002/ardp.70070

Hussein K. Seif, Dalia Mandour, Islam A. A. E.-H. Ibrahim, Mona F. Mahmoud, Mahmoud H. Elbatreek

{"title":"Nebivolol and Tadalafil Synergistically Ameliorate Insulin Resistance-Induced Retinopathy in Rats","authors":"Hussein K. Seif, Dalia Mandour, Islam A. A. E.-H. Ibrahim, Mona F. Mahmoud, Mahmoud H. Elbatreek","doi":"10.1002/ardp.70070","DOIUrl":"https://doi.org/10.1002/ardp.70070","url":null,"abstract":"<div>\u0000 \u0000 Retinopathy is a serious complication of insulin resistance. We aimed to investigate the therapeutic effect of nebivolol and/or tadalafil on insulin resistance-induced retinopathy. Insulin resistance was induced in rats using a dietary model of a high-fructose, high-fat, high-salt diet (HFrFSD). Five groups were used in the current study: standard chow diet (SCD), HFrFSD, nebivolol, tadalafil, and their half doses combination. At the end of the experiment, markers of obesity and metabolic changes were measured; moreover, changes in retinal oxidative stress, vascular reactivity, apoptosis, fibrosis, and angiogenesis markers. Histopathological changes were also recorded. Feeding rats with HFrFSD induced obesity, insulin resistance, and retinal tissue distortions, which were associated with increased retinal oxidative stress, vasculopathy, apoptosis, and angiogenesis. Both nebivolol and tadalafil did not cause significant changes in the markers of obesity, carbohydrate, and lipid metabolism, while they significantly reduced retinal tissue histopathological and molecular changes. Interestingly, the half-dose combination of nebivolol and tadalafil significantly reduced fasting blood glucose levels and insulin resistance compared with the HFrFSD group without affecting obesity markers and lipid metabolism and showed higher protective effects against retinopathy compared with the full dose individual treatments. In conclusion, nebivolol and tadalafil synergistically ameliorate insulin resistance-induced retinopathy in rats.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144807525","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