Drug Development Research最新文献

{"title":"Neuroactive Steroids Hold Promise as Innovative Anesthetics","authors":"Lu Liu,&nbsp;Yubao Li,&nbsp;Tian Mao,&nbsp;Ting Li,&nbsp;Ruilou Zhu,&nbsp;Xuhui Cong,&nbsp;Lulu Jiang,&nbsp;Mingyang Sun,&nbsp;Jiaqiang Zhang","doi":"10.1002/ddr.70137","DOIUrl":"10.1002/ddr.70137","url":null,"abstract":"<div>\u0000 \u0000 <p>Previous studies have shown that general anesthetics have neurotoxic effects on developing brains. Reducing the toxicity of anesthetics or finding nonneurotoxic anesthetics is a major challenge in anesthetic research. Neuroactive steroids (NASs) are active steroids in nervous tissue that regulate the excitability of the nervous system, γ-Aminobutyric acid subtype A receptors (GABA_ARs) serve as key targets in this regulatory process. NASs have many advantages in anesthesia, including rapid onset, mild cardiopulmonary inhibition, and neuroprotection, especially in recent studies showing that NASs do not cause neurotoxicity in the developing brain. NASs have the potential to return to human clinical applications, thereby assisting in clinical anesthesia. This article discusses the application prospects of NASs from the perspectives of action targets, drug characteristics, and neuroprotective effects, with a particular analysis of the possible mechanisms by which NASs do not induce neurotoxicity in anesthesia.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832442","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":"Ethyl Linoleate Ameliorates Synovial Cell Proliferation and Inflammatory Cell Infiltration in Rheumatoid Arthritis Through DKK1/Wnt-OPG Signal Axis and Autophagy","authors":"Zong Jiang,&nbsp;XiaoLing Yao,&nbsp;Xin Cai,&nbsp;WeiYa Lan,&nbsp;WuKai Ma,&nbsp;XueMing Yao,&nbsp;Fang Tang","doi":"10.1002/ddr.70135","DOIUrl":"10.1002/ddr.70135","url":null,"abstract":"<div>\u0000 \u0000 <p>Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease affecting synovial joints. <i>Jinwu Jiangu Capsules</i> (JJC) has been shown to be effective in treating RA. However, the primary active components and the underlying molecular mechanisms of JJC in RA treatment remain unclear. This study investigates how the monomers of JJC regulate the DKK1/Wnt-OPG signaling axis and autophagy in RA, both in vivo and in vitro. Evaluate the antiarthritis effects of JJC using a Type II collagen-induced arthritis (CIA) rat model. Histopathological analysis is conducted using HE staining, while qPCR, Western blot, ELISA, and GFP-LC3 are used to assess the DKK1/Wnt-OPG signaling pathway and autophagy status. Key components of the capsule are identified through network pharmacology. The effects of these components on osteoblasts are evaluated using CCK-8, alizarin red staining, ALP activity assay, EdU staining, MDC detection, and TRAP staining. JJC effectively reduced the expression of DKK1, RANKL, β-catenin, and p-β-catenin, while increasing the levels of autophagy-related proteins such as Beclin-1, LC3, and Atg5, thus positively affecting the progression of RA. Network pharmacology analysis revealed that ethyl linoleate (EL), a key component of JJC, targeted DKK1. RA model rats showed a dose-dependent response to EL. It significantly reduced cell proliferation and inflammatory cell infiltration in knee joint synovium and improved tissue structure. EL lowered DKK1 and RANKL levels in knee joint synovium and bone tissue, and increased OPG and LC3 expression. Additionally, it enhanced ALP activity and survival of osteoblasts, promoted cell proliferation and autophagy, protected osteoblast function, and inhibited the differentiation of PBMCs into osteoclasts, demonstrating its potential therapeutic effects on RA pathology. EL, a key component of JJC, exhibits significant therapeutic potential and positive effects in the treatment of RA by influencing the DKK1/Wnt-OPG signaling axis and autophagic processes.</p></div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832445","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":"Betulinic Acid Alleviates Acute Pancreatitis by Promoting SIRT1-PINK1-Mediated Mitophagy in Acinar Cells","authors":"Zhenfei Yu,&nbsp;Ying Li,&nbsp;Peng An,&nbsp;Xiaoling Qian,&nbsp;Yakun Wang,&nbsp;Bo Wang","doi":"10.1002/ddr.70140","DOIUrl":"10.1002/ddr.70140","url":null,"abstract":"<div>\u0000 \u0000 <p>Betulinic acid (BA) has the potential to ameliorate acute pancreatitis (AP); however, the mechanisms have not been fully elucidated. This study aimed to identify the effect of BA on mitophagy and its mediated acetylation. Rat pancreatic acinar AR42J cells were treated with cerulein to simulate AP-induced injury, and then inflammation and mitophagy were evaluated after BA treatment. The molecular mechanisms were analyzed using molecular docking, immunoprecipitation, immunoblotting, and cycloheximide chase assay. The roles of BA and SIRT1 in vivo were assessed by HE staining and enzyme-linked immunosorbent assay. The results showed that BA inhibited inflammation and promoted mitophagy in cerulein-induced AR42J cells. BA combined with SIRT1 and reduced SIRT1-mediated acetylation. Knockdown of SIRT1 counteracted the inflammation and mitophagy caused by BA. Moreover, interference with SIRT1 promoted acetylation of PINK1 to degrade PINK1 protein, which knockdown reversed the inhibition of inflammation and the promotion of mitophagy induced by SIRT1. Additionally, BA inhibited pancreatic tissue injury and inflammation levels in the pancreas in AP mice by regulating SIRT1. In conclusion, BA decelerates the progression of AP by promoting mitophagy and inhibiting inflammation in pancreatic acinar cells. Mechanically, BA increased SIRT1 expression, which knockdown degraded PINK1 protein by inducing acetylation of PINK1.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811278","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":"Synthesis and In Vitro Analysis of Dual-Functionalized Mesoporous Silica Nanoparticles for Targeted Theranosis of ER(+) Breast Cancer","authors":"Garima Mann,&nbsp;Kanchan Chauhan,&nbsp;Anupriya Adhikari,&nbsp;Karla Juarez-Moreno,&nbsp;Nikhil Kumar,&nbsp;Shivani Daksh,&nbsp;Meganathan Thirumal,&nbsp;Anupama Datta","doi":"10.1002/ddr.70138","DOIUrl":"10.1002/ddr.70138","url":null,"abstract":"<div>\u0000 \u0000 <p>Mesoporous silica nanoparticles have been extensively utilized for targeted drug delivery; the drugs are encapsulated in the pores, while the surface can be modified to make the nanoparticles target-specific. The work presented here focuses on the development of multifunctional theranostic mesoporous silica nanoparticles with estrogen receptor-positive [ER(+)] breast cancer as the target. The surface of the nanoparticles was dually functionalized to make the nanoparticles target-specific using an estradiol derivative via a facile click reaction and to attach a ^99mTc complexing agent (DTPA) for SPECT imaging. The size of the spherical nanoparticles was 80–110 nm, and the nanosystem was subjected to various physicochemical analysis techniques. Mesoporous nanoparticles were loaded with tamoxifen, an FDA-approved ER antagonist. Drug release at pH 5.8 was much more rapid than at physiological pH 7.4, a beneficial characteristic for controlled drug delivery at the tumor site. Cellular internalization and competitive binding studies indicated estradiol-mediated preferential uptake by MCF-7 cells. The nanocarrier exhibited good antiproliferative activity towards the ER(+) MCF 7 cells with a 92% decline in cellular viability in 48 h, whereas the cellular viability of the estrogen receptor-negative [ER(−)] MDA-MB-231 cells remained &gt; 60%. Thus, our results suggest a high theranostic potential of MSN-Est for breast cancer management.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811241","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, Biological Evaluation, and Computational Studies of Novel 1,4-Diketopiperazines as GABA Agonist","authors":"Mostafa Abd El-Mohsen Anwar,&nbsp;Eman R. Mohammed,&nbsp;Samir M. El Moghazy,&nbsp;Nesma M. E. Abo El Nasr,&nbsp;Marawan A. Elbaset,&nbsp;Reda M. S. korany,&nbsp;Omar Ahmed-Farid,&nbsp;Ibrahim M. Ibrahim,&nbsp;Walaa Hamada Abd-Allah","doi":"10.1002/ddr.70136","DOIUrl":"10.1002/ddr.70136","url":null,"abstract":"<div>\u0000 \u0000 <p>A novel series of 1,1-disubstituted cyclohexane <b>7a-e</b>, <b>8a-e</b>, and <b>9a-e</b> were designed, synthesized, and evaluated for their anticonvulsant activities. Compounds <b>7c</b>, <b>8c</b>, <b>8d</b>, and <b>9a</b> displayed significant anticonvulsant activity in both maximum electroshock seizure (MES) and pentylenetetrazol (PTZ) induced seizure during the preliminary screening with no neurotoxicity. The phase II quantitative anticonvulsant activity revealed that compound <b>8c</b> demonstrated the most potent activity as compared to the conventional drugs phenobarbital. The expression of nuclear factor erythroid 2-related factor- antioxidant response element (Nrf2-ARE) signaling pathways, oxidative stress parameters were also observed. Additionally, histopathological examination of brain of animals treated with compounds <b>7c</b>, <b>8c</b>, <b>8d</b>, and <b>9a</b> was performed and the results were corroborated the neuroprotective properties. Further neurochemical investigation was performed to unravel the effect of the most active compounds, compounds <b>7c</b>, <b>8c</b>, <b>8d</b>, and <b>9a</b> demonstrated significant protection by ameliorating GABA levels, which were initially reduced to 61% by PTZ administration, suggesting enhanced GABAergic neurotransmission. Computational parameters including docking analysis on GABAA exhibiting good binding on the active site, Moreover, In silico prediction was carried out indicating that most of compounds have favorable oral bioavailability and BBB permeability they might be viewed as helpful models for future research and derivatization.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811240","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":"Investigating the Effects of Curcumin on Lipid Metabolism and Cell Viability in HepG2 Cells: Potential Therapeutic Implications for Nonalcoholic Fatty Liver Disease","authors":"Faeze Qaleban,&nbsp;Javad Mohammadnejad,&nbsp;Amin Daemi,&nbsp;Gülüzar Özbolat,&nbsp;Yusuf Döğüş","doi":"10.1002/ddr.70142","DOIUrl":"10.1002/ddr.70142","url":null,"abstract":"<div>\u0000 \u0000 <p>Metabolic dysfunction-associated steatotic liver disease (MASLD), poses a significant global health challenge, necessitating novel therapeutic strategies. This study investigates examines the efficacy of curcumin (Cur), a natural bioactive compound, in suppressing inhibiting the proliferation of hepatocellular carcinoma proliferation and reducing lipid accumulation in vitro. HepG2 cells were treated with Cur (1.25–10 μg/mL) for 24–72 h, revealing a dose- and time-dependent reduction in viability, with an IC50 of 10 µg/mL at 72 h. Oil Red O staining demonstrated Cur's lipid-lowering effects, reducing lipid content by 57% at 5 µg/mL and 78% at 10 µg/mL, suggesting enhanced efficacy at higher concentrations. Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) analysis revealed that Cur downregulated key lipogenic regulators Peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBP-α) by 2.3- and 1.8-fold, respectively, while modulating 14-3-3γ/β expression, implicating these pathways in its mechanism. These findings highlight Cur's potential to attenuate hepatic lipid accumulation and cancer cell growth in vitro, warranting further validation in primary hepatocytes and preclinical models to advance its therapeutic prospects for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798452","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":"KNK437 Suppresses the Growth of Non-Small Cell Lung Cancer Cells by Targeting Heat Shock Factor 1","authors":"Lili Wu,&nbsp;Jieni Feng,&nbsp;Hualong Lin,&nbsp;Peirui Chen","doi":"10.1002/ddr.70141","DOIUrl":"10.1002/ddr.70141","url":null,"abstract":"<div>\u0000 \u0000 <p>Heat shock factor 1 (HSF1) has emerged as a promising therapeutic target in various solid tumors. However, its specific role in non-small cell lung cancer (NSCLC) and the potential efficacy of HSF1 inhibitors in this context remain largely unexplored. The current data showed that HSF1 is overexpressed in NSCLC cells and is positively associated with poorer survival outcomes in NSCLC patients. Moreover, the HSF1 inhibitor KNK437 markedly suppresses NSCLC cell proliferation and induces dose-dependent cell cycle arrest and apoptosis. In addition, KNK437 significantly alters the expression of HSF1 and its downstream target genes in HSF1-overexpressing NSCLC cells, while HSF1 knockdown markedly attenuates the anti-proliferative effects of KNK437, indicating that its therapeutic efficacy is largely mediated through HSF1 inhibition. Finally, molecular docking simulations revealed that KNK437 engages in hydrophobic interactions and forms two critical hydrogen bonds with HSF1, potentially underpinning its inhibitory activity. Collectively, these findings support HSF1 as a compelling molecular target for NSCLC treatment and highlight KNK437 as a promising therapeutic candidate.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793711","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":"Transcription Factor MYB Upregulates IQGAP3 to Mediate DNA Repair and Promote 5-FU Resistance in Gastric Cancer Cells","authors":"Lizhe Huang,&nbsp;Piyao Gao,&nbsp;Pengcheng Xiao,&nbsp;Zhongyang Chen,&nbsp;Sen Zhang","doi":"10.1002/ddr.70134","DOIUrl":"10.1002/ddr.70134","url":null,"abstract":"<div>\u0000 \u0000 <p>5-Fluorouracil (5-FU)-based chemotherapy is a first-line treatment for advanced gastric cancer (GC); however, the development of resistance remains a major limitation to its clinical efficacy. This study aims to investigate the role of the MYB/IQGAP3 axis in mediating 5-FU resistance in GC. Using bioinformatics, we analyzed expression profiles of IQGAP3 and MYB in GC tissues and pinpointed their binding sites. IHC was used to detect the expression of IQGAP3 in GC tissues. The signaling pathways potentially regulated by IQGAP3 were also investigated. Dual-luciferase and chromatin immunoprecipitation assays substantiated the regulatory link between MYB and IQGAP3. Expressions of IQGAP3, MYB, and drug-resistant genes were measured via qRT-PCR and western blot. The CCK-8 assay was implemented to gauge cell survival and the IC50 values. The colony formation assay assessed cell growth. Cell apoptosis was examined by flow cytometry. DNA damage was visualized by immunofluorescence staining. We detected a pronounced enhancement in the expression of IQGAP3 and MYB within GC tissues and cells and identified that IQGAP3 was involved in the regulation of mismatch repair and DNA repair (DNAR) pathways. Suppression of IQGAP3 led to increased sensitivity to 5-FU, as evidenced by a decreased IC50 value. Along with that, we observed increased apoptosis and restrained proliferation of GC cells, downregulated P-gp, MRP1, and GST-π protein levels, and hindered DNAR. The effects were inverted with the overexpression of IQGAP3. Furthermore, MYB could bind to IQGAP3 promoter to promote its transcription, and silencing IQGAP3 substantially negated the influence of MYB overexpression on GC cell DNAR and sensitivity to 5-FU. The upregulation of IQGAP3 by MYB mediates DNAR, thereby promoting 5-FU resistance in GC. This points to the therapeutic value of targeting MYB/IQGAP3 to reduce GC drug resistance and enhance the clinical efficacy of treatments.</p></div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793712","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":"Comparative Study of Conventional, Grinding, and Microwave-Assisted Synthesis of Aminopyrazolones and Diaminopyrazoles: Exploring the Antitumor Activity, Dual CDK-2/CA IX Inhibition Potential, and Apoptosis Induction","authors":"Kurls E. Anwer,&nbsp;Nehad M. El-Dydamony,&nbsp;Asmaa Saleh,&nbsp;Najla Altwaijry,&nbsp;Ebtehal M. Husseiny","doi":"10.1002/ddr.70139","DOIUrl":"10.1002/ddr.70139","url":null,"abstract":"<div>\u0000 \u0000 <p>Embracing drug design approaches including ring variation, substituent variation, and bioisosteric modifications, aminopyrazolones <b>2–7</b> and diaminopyrazoles <b>9–14</b> were synthesized as dual potent CDK-2 and CA IX inhibitors for the first time. The eco-friendly preparation of the target analogs was performed by three procedures: conventional, grinding, and microwave-assisted methods. The synthesized congeners were estimated for their antitumor effect against breast MCF-7, hepatocellular HepG2, and colon HCT-116 cells where the aminopyrazolones <b>4</b> and <b>7</b> presented significant cytotoxicity against the examined carcinomas. Compound <b>4,</b> bearing a dinitrophenyl ring at <i>N</i>-2 of aminopyrazolone scaffold, exhibited the greatest cytotoxicity and selectivity toward the tested cell lines. Hence, compounds <b>4</b> and <b>7</b> were selected for consecutive biological assays to determine their mode of action. The findings proposed that <b>4</b> and <b>7</b> may exert their antiproliferative activity via interaction with CDK-2 and CA IX receptors. Entity <b>4</b> exhibited promising dual inhibition of CDK-2 and CA IX with IC₅₀ at the micromolar level, which exceeded that of Roscovitine by three times and nearly half that of acetazolamide. Additionally, the superior derivative <b>4</b> stimulated MCF-7 cycle arrest at S phase through apoptotic induction which is supported by the upregulation of Bax and Caspase-8 and the downregulation of Bcl-2 and Cyclin E. The in silico studies showed acceptable predicted ADME and physicochemical properties together with the strong interaction between the superior compounds and both CDK-2 and CA IX binding sites inspiring such hybrids as potential lead dual inhibitors.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782595","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":"Quinolone as a Privileged Scaffold: A Brief Overview on Early Classical and Recent Advanced Synthetic Pathways, Innovative Neuroprotective Potential, and Structure-Activity Relationships","authors":"Esraa Abdo Moustafa,&nbsp;Nahed Nasser Eid El-Sayed,&nbsp;Marwa A. Fouad,&nbsp;Ahmed M. El Kerdawy,&nbsp;Manal Abdel Fattah Ezzat,&nbsp;Heba Abdelrasheed Allam","doi":"10.1002/ddr.70132","DOIUrl":"10.1002/ddr.70132","url":null,"abstract":"<div>\u0000 \u0000 <p>Neurodegenerative disorders represent the second largest group of diseases worldwide. 2(1<i>H</i>)-quinolone and its structural congener, 4(1<i>H</i>)-quinolone have recently become significant topics in the field of drug design and development of modulators of neurotransmitter systems and neuroprotective agents to tackle neurodegenerative disorders. In this review, the structural properties and the early classical as well as the recent novel synthetic strategies for 2(1<i>H</i>)-/4(1<i>H</i>)-quinolone are discussed. The neuropharmacological activity and mechanisms of action of several 2(1<i>H</i>)-/4(1<i>H</i>)-quinolinone-based compounds are demonstrated with special emphasis on the structure–activity relationships (SAR). Therefore, the perspectives elaborated in this review could guide medicinal chemists for rational design and development of novel 2(1<i>H</i>)-/4(1<i>H</i>)-quinolone therapeutic candidates targeting neurodegenerative diseases.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767818","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}