Medicinal Chemistry最新文献

{"title":"Discovery of Novel 1,3,4-oxadiazole-based Inhibitors Against Urease and Diabetes: Design, Synthesis, SAR, Biological, and Molecular Docking Screening.","authors":"Sabeen Arshad, Aneela Maalik, Wajid Rehman, Yousaf Khan, Hina Sarfraz, Liaqat Rasheed, Mohammed B Hawsawi, Mustafa S Alluhaibi, Majed Alharbi","doi":"10.2174/0115734064385863250815045326","DOIUrl":"10.2174/0115734064385863250815045326","url":null,"abstract":"<p><strong>Introduction: </strong>Heterocyclic compounds bearing oxygen and nitrogen atoms are key pharmacophores in modern drug design. Among them, 1,3,4-oxadiazoles are notable for their diverse biological activities, including anti-inflammatory, anticancer, antidiabetic, antibacterial, and enzyme inhibitory effects. This study focuses on the synthesis and evaluation of indazole-based 1,3,4-oxadiazole-benzenesulfonothioate hybrids as potential therapeutic agents.</p><p><strong>Methods: </strong>A multistep synthetic route was employed to develop a series of eighteen (18) analogues. The synthetic strategy involved the formation of methyl 5-methyl-1H-indazole-3-carboxylate, conversion to carbohydrazide, cyclization with CS2, and final coupling with substituted benzenesulfonyl chlorides to yield the target hybrids (1-18).</p><p><strong>Results: </strong>The urease inhibition potential of scaffolds ranged from IC₅₀ = 17.88 ± 0.36 to 37.98 ± 0.80 μM as compared to the standard drug thiourea (IC₅₀ = 29.45 ± 0.76 μM). The exceptional urease and α-glucosidase activity was shown by scaffolds (4, 7, 9, 11) due to the presence of electron- withdrawing groups (-F, NO₂, and Cl). In comparison, the α-glucosidase inhibition potential shown by all the scaffolds was in the range (IC₅₀ = 3.19 ± 0.27 - 12.24 ± 1.33 μM). Compound-9 showed promising inhibitory potential against urease, with an IC₅₀ = 17.90 ± 0.30 μM, and α- glucosidase (IC₅₀ = 3.19 ± 0.27 μM), both indicating minimum IC₅₀ values.</p><p><strong>Discussion: </strong>The enhanced activity of compounds bearing electron-withdrawing groups (F, NO₂, Cl) supports their role in modulating enzyme inhibition. In silico molecular docking further confirmed strong binding affinities with the active sites of target enzymes, correlating well with the experimental results.</p><p><strong>Conclusion: </strong>The synthesized 1,3,4-oxadiazole derivatives demonstrate promising dual inhibitory activity against urease and α-glucosidase, suggesting their potential as lead compounds in the treatment of gastric infections and diabetes. This study contributes to the ongoing development of multifunctional therapeutic agents with improved efficacy and selectivity.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"376-398"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding Therapeutic Horizons with Indazole-Based Compounds: A Review of Anticancer, Antimicrobial, and Neuroprotective Applications.","authors":"Pooja Dinkar Bhane, Sarita Suryabhan Pawar","doi":"10.2174/0115734064371097250403114905","DOIUrl":"10.2174/0115734064371097250403114905","url":null,"abstract":"<p><p>Indazole-based compounds have recently developed and physiologically evaluated as diverse agents for antibacterial, anticancer, anti-inflammatory, anti-obesity, and neurological therapies. This review highlights these advancements. Through molecular docking and experimental tests, scientists have created distinct indazole analogs that exhibit significant inhibitory effects on various biological targets, including 1,2,3-triazolyl-indazoles, carbothioamides, and carboxamides. Key compounds have demonstrated strong bactericidal and antifungal properties against microbes such as <i>S. epidermidis, P. aeruginosa, E. coli</i>, and <i>C. albicans</i>; their effectiveness was enhanced by halogenated and electron-withdrawing substituents. In models including positive HER2 breast cancer and hepatocellular tumors, indazole derivatives have shown efficacy against targets such as CDK2, EGFR, c-Met, HSP90, and VEGFR2 in oncology, resulting in successful anticancer responses. The pharmacokinetics, solubility, and specificity of these compounds have been further improved through structural alterations, such as piperazine ring modifications and C-terminal changes. Additionally, the LRRK2 antagonist MLi-2 demonstrated remarkable efficacy in treating neurodegenerative diseases, while indazole-5-carboxamides exhibited a strong affinity for monoamine oxidases, potentially offering new therapeutic options for Parkinson's disease. Inhibition of COX-2 and FGFR resulted in anti-inflammatory effects, with minimal off-target damage observed in vivo. Collectively, our findings underscore the therapeutic versatility of indazole frameworks across various disease pathways, suggesting their potential for developing innovative treatments for cancer, infections, metabolic disorders, and neurological conditions.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"30-56"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, and Biological Evaluation of a Novel Series of Thiazolidinediones as Dual GSK-3β and Tau Aggregation Inhibitors.","authors":"Zahra Abdollahi, Khalil Abnous, Mohamad Reza Kalani, Seyed Mohammad Taghdisi, Somaieh Soltani, Mojgan Nejabat, Farzin Hadizadeh","doi":"10.2174/0115734064369119250413021648","DOIUrl":"10.2174/0115734064369119250413021648","url":null,"abstract":"<p><strong>Introduction: </strong>Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase that is involved in the synthesis of glycogen. Among the inhibitors, thiazolidinediones (TZDs) can specifically bind to GSK-3β. They act non-competitively with ATP, and as a result, they are very specific and have fewer side effects. In this research, new TZDs were designed and synthesized, and then their inhibitory effects on GSK-3β enzyme and tau aggregation were investigated.</p><p><strong>Materials and methods: </strong>The structure of the compounds was confirmed using 1H-NMR, 13CNMR, and LC-MASS. The inhibitory activities of the compounds 5a-p, against GSK-3β were evaluated using Z'-LYTE technique, and the IC50 values were determined.</p><p><strong>Results: </strong>Compound 5l (R1 = Me, R2 = 4-F-benzyl, R3 = butyl) with IC50 of 16.1 μM exhibited the most potent inhibition. Also, the binding with tau protein and their inhibitory effects on the accumulation of recombinant human tau protein (1N4R, htau34) were evaluated using the Surface Plasmon Response (SPR) method. In this study also the impact of TZDs on tau aggregation using the Thioflavin T (ThT) assay was investigated. PC12 cells viability study confirmed the neuroprotective effects of compounds against tau aggregates. MD simulation studies showed the interaction of 5l with the active site of GSK-3β (PDB ID: 2OW3) and also its destructive effect on tau aggregate (PDB ID: 5O3L) was studied.</p><p><strong>Conclusion: </strong>Overall, the study identified three promising TZDs with potential as inhibitors of GSK-3β and tau proteins, highlighting compound 5l as particularly effective in stabilizing GSK- 3β and disrupting tau aggregation.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"193-211"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Synthesis, Pharmacological Activities, Structure-activity Relationship of 1,3,4-Oxadiazole-Piperazine Conjugates: A Review.","authors":"Upasana Sharma, Rajnish Kumar, Avijit Mazumder, Salahuddin, Pankaj Kumar Tyagi, Saurabh Singh","doi":"10.2174/1573406422999260112155851","DOIUrl":"https://doi.org/10.2174/1573406422999260112155851","url":null,"abstract":"<p><p>Following the publication of this article [1], it was noted that some chemical structures were misnumbered during processing of the text. This has now been corrected in the text and Table 5. The original article can be found online at: https://www.eurekaselect.com/article/144767.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"22 4","pages":"399-400"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, and Biological Evaluation of Novel 7-Hydroxycoumarin- Based <i>N</i>-Hydroxyamides as Histone Deacetylase Inhibitors and Cytotoxic Agents.","authors":"Tran Duy Thanh, Vu Xuan Thach, Luu Van Chinh, Dinh Thi Phuong Anh, Do Thi Thao, Duong Quang Quy, Hai Pham-The, Tran Khac Vu","doi":"10.2174/0115734064402162251011065534","DOIUrl":"https://doi.org/10.2174/0115734064402162251011065534","url":null,"abstract":"<p><strong>Introduction: </strong>Histone deacetylases (HDACs) play a crucial role in gene expression, and their dysregulation is linked to various cancers. HDAC inhibitors, particularly hydroxamic acid derivatives, have shown promising anticancer effects, with several approved for clinical use. This research aimed to synthesize novel 7-hydroxycoumarin-based N-hydroxyamides, evaluate their HDAC inhibition, and assess their in vitro cytotoxic effects.</p><p><strong>Methods: </strong>The structures of the synthesized compounds were established by analysis of their physicochemical, elemental, and spectroscopic data. HDAC, in vitro assays, and molecular docking were performed using standard procedures.</p><p><strong>Results: </strong>The biological results showed that compounds 5d, 5e, 5j, 5l, and 7k exhibited potential cytotoxicity toward all five cancer cell lines. These compounds displayed potent cytotoxicity against the NCCIT cancer cell line with IC50 values of 4.53-1.45 μM. However, they exhibited weak to medium HDAC inhibitory activity with IC50 values ranging from 21.72 to 4.79 μM. Docking simulation studies with selected compounds revealed that compounds 5a and 7k formed stable interactions in the active site of HDAC enzyme with binding affinities ranging from -7.43 to -7.103 kcal/mol, respectively.</p><p><strong>Discussion: </strong>The study revealed several compounds with potential HDAC inhibitory activity and cytotoxicity. However, they were still less effective in inhibiting HDACs than SAHA and Trichostatin A. Their reduced potency may be related to the length of the linker linked to the surface recognition group. This provides important insight into the future design of hydroxamic acids of this type.</p><p><strong>Conclusion: </strong>The research results suggest that some hydroxamic acids (5a and 7k) warrant further evaluation, and these results could serve as a basis for designing more potent HDAC inhibitors and antitumor agents.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virtual Screening of FDA-Approved Drugs on Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) to Obtain New Trypanocidal Agents.","authors":"Alfredo Juarez-Saldivar, Lenci K Vazquez-Jimenez, Eyra Ortíz-Pérez, Rogelio Gomez-Escobedo, Benjamin Nogueda-Torres, Gildardo Rivera","doi":"10.2174/0115734064408199251003102853","DOIUrl":"https://doi.org/10.2174/0115734064408199251003102853","url":null,"abstract":"<p><strong>Introduction: </strong>The protozoan parasite Trypanosoma cruzi (T. cruzi) is the etiologic agent of Chagas disease, also known as American trypanosomiasis, which primarily affects the Americas and is highly prevalent in developing countries. Treatment consists of the drugs nifurtimox and benznidazole; however, both drugs have variable efficacy and cause serious adverse effects. In T. cruzi, the enzyme glyceraldehyde 3-phosphate dehydrogenase (TcGAPDH) plays an essential role in energy production and additional nuclear functions, making it a pharmacological target for the development of new trypanocidal agents. In this study, the objective was to identify new potential TcGAPDH inhibitors with trypanocidal activity.</p><p><strong>Methods: </strong>A virtual screening based on molecular docking of FDA-approved drugs was performed, followed by in vitro biological evaluation of trypomastigotes from two T. cruzi strains.</p><p><strong>Results: </strong>Seven FDA-approved drugs (pemetrexed, gliquidone, irbesartan, enoxacin, norfloxacin, pazopanib, and fenoprofen) had the best affinity values and a suitable interaction profile at the active site of the TcGAPDH enzyme, which had better LC50 values than the reference drugs.</p><p><strong>Discussion: </strong>Drug repositioning using computer-aided methods reduces cost and time to find new pharmacological treatments. In this study, gliquidone (antidiabetic), irbesartan (antihypertensive), pemetrexed, and pazopanib (anticancer) are drugs with high trypanocidal activity that could be candidates for evaluation in clinical phases or used to develop new drugs to combat Chagas disease. It highlights fenoprofen, an anti-inflammatory agent, which has biological properties that help to reduce the symptomatology of the disease in the chronic stage. Additionally, it is necessary to study the mechanism of action of these compounds in detail to confirm if they have an effect on the proposed pharmacological targets.</p><p><strong>Conclusion: </strong>Seven FDA-approved drugs are candidates for further studies leading to the development of potential new treatments for Chagas disease.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quinolones: The Cornerstone of the Advanced Era in Therapeutics.","authors":"Priyanshi Choudhary, Manisha Bhatti","doi":"10.2174/0115734064392227250918071711","DOIUrl":"https://doi.org/10.2174/0115734064392227250918071711","url":null,"abstract":"<p><p>Quinolones are nitrogen-containing heterocyclic compounds that exist in natural, semisynthetic, and synthetic forms, and play a vital role as antibiotics. Their complex structure and numerous potential modifications have made them a significant focus in synthetic chemistry over the past two to three decades. The most common compound associated with quinolones is nalidixic acid, which was discovered long ago. Since then, various researchers have focused on this core as a potential pharmacophore or starting nucleus for developing new drug candidates to manage diseases, such as cancer, urinary tract infections, Alzheimer's, and tuberculosis. In this paper, we aimed to summarize the activities of quinolone hybrids discovered over the past decades. The article delivers a thorough overview of quinolones with emphasis on synthetic innovations, their mechanism of action, resistance evasion, and classification from generation to generation, along with the newer agents. Furthermore, emerging concepts, including modulation of SOS response, induction of oxidative stress, and impact of sub-inhibitory concentrations, are also explored as supplementary strategies to enhance antibacterial efficacy. Beyond their well-known antibacterial activity, quinolones also exhibit a broad range of pharmacological properties, including antimalarial, antifungal, antiinflammatory, antitubercular, anticancer, antiviral, and immunomodulatory effects. This review highlights both their diverse clinical applications and the challenges associated with their use. This article also provides a knowledgeable asset for acknowledging quinolones' chemistry, pharmacology, and future therapeutic potential.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxindole Analogues as Anticancer Agents and their Therapeutic Potential.","authors":"Shilpi Pathak, Kenika Sharma, Anmol Goswami, Paras Singh","doi":"10.2174/0115734064402335250929182136","DOIUrl":"https://doi.org/10.2174/0115734064402335250929182136","url":null,"abstract":"<p><p>Oxindole and its derivatives have emerged as interesting scaffolds for developing innovative anticancer medicines due to their various biological activities and capacity to target critical molecular pathways in cancer growth. The oxindole nucleus has powerful anticancer capabilities, which are exerted through various methods, including kinase inhibition, apoptosis induction, disruption of microtubule dynamics, and signaling pathway modification (PI3K/Akt, MAPK, and p53). Furthermore, oxindole-based drugs have been beneficial in combating multidrug resistance and improving the efficacy of existing chemotherapeutic treatments. The current review examines the anticancer potential of the oxindole nucleus, including structure-activity correlations, molecular targets, and methods of action. Furthermore, we discuss current advances in oxindole-derived drug design and its clinical implications, providing insights into prospective therapeutic possibilities. Understanding the molecular characteristics of oxindole derivatives can help in the rational development of new anticancer medicines with higher efficacy and selectivity.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Therapeutic Potential of 8-Hydroxyquinoline: A Multi-Targeting Approach.","authors":"Riddhisiddhi Patel, Drashti Shah, Ashish Patel","doi":"10.2174/0115734064392352250904122732","DOIUrl":"https://doi.org/10.2174/0115734064392352250904122732","url":null,"abstract":"<p><p>In recent years, extensive research has been conducted by medicinal and organic chemists on derivatives of 8-Hydroxyquinoline (8-HQ) due to their potential as therapeutic agents for a wide range of diseases and disorders. These derivatives show promise in treating conditions such as cancer, HIV, tuberculosis, and neurodegenerative disorders. Additionally, the ability of 8-HQ to chelate metal ions adds to its value as a scaffold for developing treatments for various diseases. Over the past two decades, significant efforts have been made to create drug molecules based on 8- HQ that exhibit excellent therapeutic potency against different therapeutic targets. Recognizing the significance of 8-HQ in the field of therapeutics, this review provides an overview of its reported therapeutic activity in the literature over the past two decades. The review also addresses the challenges and opportunities in the development of 8-HQ, suggesting future research directions in this area.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypolipidemic and Hepatoprotective Effects of 5-(4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)Pentanoic Acid (TDPPA) on Hyperlipidemic Mice.","authors":"Ting Li, Manjun Liu, Qiuzhen Yuan, Wenjing Shen, Xueyou Chen, Lei Zhang, Yundong Xie","doi":"10.2174/0115734064425298250923050512","DOIUrl":"10.2174/0115734064425298250923050512","url":null,"abstract":"<p><strong>Introduction: </strong>Hyperlipidemia is a prevalent condition that accelerates the development of cardiovascular diseases. Traditional treatments targeting lipid regulation often have limitations, such as hepatotoxicity. This study investigates the dual action of a novel compound, 5-(4-(3-thioxo- 3H-1,2-dithiol-5-yl)phenoxy)pentanoic acid (TDPPA), in reducing lipid levels and protecting the liver.</p><p><strong>Methods: </strong>TDPPA was synthesized and structurally confirmed by 1H-NMR, 13C-NMR, and HRMS. Its lipid-lowering efficacy was first assessed in Triton WR-1339-induced acute hyperlipidemic mice. Mechanistic studies were then conducted in a high-fat emulsion-induced chronic hyperlipidemia model, incorporating histopathological analysis of the liver (H&E and Oil Red O staining). Liver index, serum lipid panels, hepatic function markers, HⁿS content, oxidative stress parameters, and pro-inflammatory cytokines were quantified via ELISA, while the interaction between TDPPA and PPAR-α was evaluated by molecular docking and Western blotting.</p><p><strong>Results: </strong>TDPPA significantly reduced serum triglyceride (TG), total cholesterol (TC), and lowdensity lipoprotein cholesterol (LDL-C) in both acute and chronic models, while increasing highdensity lipoprotein cholesterol (HDL-C). Histology revealed marked reductions in hepatic lipid accumulation and inflammatory infiltration. Biochemical assays showed decreases in AST and ALT, enhanced antioxidant capacity (higher SOD and HⁿS, lower MDA), and suppression of TNF- α, IL-6, and IL-1β. Molecular docking and Western blot analysis indicated that these effects were associated with upregulation of PPAR-α protein expression.</p><p><strong>Discussion and conclusion: </strong>TDPPA demonstrates potent lipid-lowering, antioxidant, and antiinflammatory activities, likely through a dual mechanism involving PPAR-α activation and HⁿSmediated hepatoprotection. These findings position TDPPA as a promising therapeutic candidate for hyperlipidemia with the benefit of liver protection.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}