MedChemComm最新文献

{"title":"Pegylation approach applied to erlotinib–carbonic anhydrase inhibitors hybrids towards anticancer agents†","authors":"Serena Filiberti, Gioele Renzi, Fabrizio Carta, Marialuigia Fantacuzzi, Ilaria D'Agostino, German Benito, Andrea Angeli, Maria Luisa Massardi, Rahime Simsek, Clemente Capasso, Simone Carradori, Roberto Ronca and Claudiu T. Supuran","doi":"10.1039/D5MD00109A","DOIUrl":"10.1039/D5MD00109A","url":null,"abstract":"<p >Herein we report a first study on single molecular entities bearing both epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA) inhibiting moieties as new tools for the management of hypoxic cancers. Specifically, we designed and synthesized a library of erlotinib (<strong>ERL</strong>)-based compounds bearing both the primary sulfonamide/coumarin moieties with the intent to selectively interfere with EGFR and CA targets respectively. The compounds obtained were investigated <em>in silico</em> and <em>in vitro</em> for their ability to interact with the appropriate targets followed by the assessment on selected compounds for the anti-proliferative activity using human (h) TNBC cell line MDA-MB-231. We are confident that the data provided in this study are fundamental for paving the way toward the development of multi-targeting molecular structures useful for the management of chronic diseases such as hypoxic tumors.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 9","pages":" 4316-4339"},"PeriodicalIF":3.597,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Trypanosoma brucei acting derivatives incorporating 1-(4-phenyl)adamantane and 1-(4-phenoxyphenyl)adamantane†","authors":"Konstantina Stavropoulou, Angeliki Kaimaki, Maria Nikolaou, Ana K. Brown, Andrew Tsotinis, Martin C. Taylor, John M. Kelly and Ioannis P. Papanastasiou","doi":"10.1039/D5MD00135H","DOIUrl":"10.1039/D5MD00135H","url":null,"abstract":"<p >In this work, we describe the design, synthesis and evaluation of novel functionalised 1-(4-phenyl)adamantane and 1-(4-phenoxyphenyl)adamantane derivatives. Based on previous findings, we incorporated a phenyl ring between the adamantane core and the pharmacophoric side chain to enhance the activity and selectivity index (SI). The aromatic imidazolines <strong>1a–d</strong> and the linear amidines <strong>2a</strong>,<strong>b</strong> and <strong>3a</strong>,<strong>b</strong> exhibited notable activity against <em>T. brucei</em>. The 1-(4-phenyl)adamantane 1-(4-phenoxyphenyl)adamantane core was further functionalized with the aminoguanylhydrazone and thiosemicarbazone moieties. 2-[(<em>E</em>)-4-(1-adamantyl)benzylidene]hydrazine-1-carbothioamide <strong>4c</strong> emerged as a promising trypanocidal agent with an EC<small>₅₀</small> of 0.16 μM and an SI of 17. Future studies will focus on optimizing the length and the distance of the side chain between the aromatic ring and the chromophores to further enhance the activity and selectivity of these molecules.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 6","pages":" 2441-2451"},"PeriodicalIF":3.597,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human chitinases and chitinase-like proteins as emerging drug targets – a medicinal chemistry perspective","authors":"Önder Kurç, Nick Rähse, Holger Gohlke and Jonathan Cramer","doi":"10.1039/D4MD01050G","DOIUrl":"10.1039/D4MD01050G","url":null,"abstract":"<p >Human chitinases and chitinase-like proteins (CLPs) provide the immune system with the ability to recognize or process chitin originating from chitinous pathogens. In addition to their role in host defense, most members of this protein family have evolved pleiotropic cellular effector functions broadly related to immune homeostasis, cell proliferation, and tissue remodeling. This wide-ranging ability to modulate crucial cellular processes proceeds <em>via</em> the activation of cellular signal transduction cascades and appears to be fully independent of chitin recognition. Dysregulation of chitinase/CLP functions has been linked to a plethora of inflammatory diseases, such as allergic airway diseases and asthma, fibrosis, as well as cancer. This fact predetermines certain members of this protein family as prime targets for pharmacological intervention. Here, we provide an extensive review of medicinal chemistry efforts targeting the most widely studied members of the human chitinase/CLP family, namely acidic mammalian chitinase (AMCase), chitotriosidase (CHIT1), and chitinase-3-like protein 1 (CHI3L1/YKL-40).</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 6","pages":" 2388-2402"},"PeriodicalIF":3.597,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromenochalcones: a comprehensive review on developments towards a medicinal perspective","authors":"Rohit Singh, Archita Katrolia and Ved Pal","doi":"10.1039/D5MD00062A","DOIUrl":"10.1039/D5MD00062A","url":null,"abstract":"<p >Chalcones are indeed a versatile scaffold in medicinal chemistry. Their structure, featuring an α,β-unsaturated carbonyl group, makes them highly reactive and capable of interacting with various biological targets. This reactivity is a key reason why chalcones and their derivatives are of such interest in drug discovery. The continued exploration of chalcone derivatives in medicinal chemistry will likely yield new insights and therapeutic candidates, given their broad spectrum of biological activities and the flexibility in modifying their structures. As chalcone derivatives, pyranochalcones and chromanchalcones are members of a subclass of flavonoids that are widely distributed. Several scientific databases were investigated to compile articles that illustrated the biological functions of chromenochalcones and their derivatives. Preclinical research on chromenochalcones and their derivatives is well covered in this review, highlighting the compounds with enormous significance as antimalarial, anti-inflammatory, antileishmanial, cytotoxic, antibacterial, antifungal, and antioxidant agents. In addition, the article briefly discusses the synthetic pathways employed for the total synthesis of selected pyranochalcones, including mallaophilippens C and E, citrunobin, and lesperol. Consequently, this overview may help research and design novel, potent therapeutic medications based on previously developed methodologies. This review is intended to provide a thorough, authoritative, and critical assessment of the chromenochalcone template for the chemistry community.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 7","pages":" 2919-2936"},"PeriodicalIF":3.597,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New acridone derivatives to target telomerase and oncogenes – an anticancer approach†","authors":"Tiago J. S. Marques, Diana Salvador, Helena Oliveira, Vanda V. Serra, Nicholas Paradis, Chun Wu, Vera L. M. Silva and Catarina I. V. Ramos","doi":"10.1039/D4MD00959B","DOIUrl":"10.1039/D4MD00959B","url":null,"abstract":"<p >In this work, two new acridone derivatives, <strong>AcridPy</strong> and <strong>AcridPyMe</strong>, were synthesized, for the first time, aiming to evaluate their potential as quadruplex stabilizers and anticancer agents. <strong>AcridPy</strong> was synthesized through a very straightforward one-pot sequential chemical reaction involving the Heck cross-coupling reaction of (<em>E</em>)-3-iodo-2-(4-methoxystyryl)-1-methylquinolin-4(1<em>H</em>)-one with a vinyl pyridine followed by <em>in situ</em> electrocyclization and oxidation, while the synthesis of <strong>AcridPyMe</strong> involved an additional <em>N</em>-methylation of the pyridine ring. Their ability to stabilize G-quadruplex DNA structures, which are associated with the regulation of oncogenes, was assessed using biophysical methods. Both compounds demonstrated significant quadruplex stabilization properties, showing selectivity to G-quadruplexes over duplex DNA. Molecular dynamics simulation experiments supported the preferential binding of <strong>AcridPyMe</strong> to MYC. The cytotoxicity of these derivatives was further evaluated <em>in vitro</em> in two distinct pancreatic tumor cell lines, PanC-1 and MIA PaCa-2, the lung tumor A549 cell line, the melanoma A375 cell line, and the immortalized human keratinocyte HaCaT cell line, through the evaluation of cell viability. For PanC-1 and MIA PaCa-2, the cell cycle dynamics and apoptotic cell death along with colocalization were also evaluated. The results revealed that <strong>AcridPyMe</strong> exhibited anticancer activity, correlated with its quadruplex stabilization ability and, although not exclusive, nuclear co-localization was observed. These findings suggest that the newly synthesized cationic acridone is a promising candidate for the development of novel anticancer therapies targeting G-quadruplex structures.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 6","pages":" 2785-2807"},"PeriodicalIF":3.597,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, characterization and biological activity of methotrexate-derived salts in lung cancer cells†","authors":"Dário Silva, Sandra Cordeiro, Pedro V. Baptista, Alexandra R. Fernandes and Luis C. Branco","doi":"10.1039/D4MD00960F","DOIUrl":"10.1039/D4MD00960F","url":null,"abstract":"<p >Lung cancer is one of the deadliest types of cancer, and is a public health problem worldwide. Methotrexate (MTX), a class IV drug in the biopharmaceutical classification system, is a folate antagonist that has demonstrated efficacy in cancer treatment. A suitable combination of MTX as a di-anion and biocompatible counter ions allowed the modulation of their physicochemical properties. In this work, twelve MTX salts were prepared and characterized by <small>¹</small>H NMR, <small>¹³</small>C NMR, and elemental analysis. The antiproliferative effects of MTX salts were studied in A459 and H1975 (lung cancer cell lines) with three promising results: [C<small>₁₂</small>mim]<small>₂</small>[MTX] (IC<small>₅₀</small> = 0.55 ± 0.25) &gt; [C<small>₁₀</small>-3-picoline]<small>₂</small>[MTX] (IC<small>₅₀</small> = 0.94 ± 0.03) &gt; [C<small>₁₀</small>mim]<small>₂</small>[MTX] (IC<small>₅₀</small> = 1.71 ± 0.23) in A549. These three MTX salts also demonstrated intrinsic apoptosis, avoiding necrosis and the formation of reactive oxygen species.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 8","pages":" 3593-3602"},"PeriodicalIF":3.597,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro evaluation of the immunogenic potential of gramicidin S and its photocontrolled analogues†","authors":"Kateryna Horbatok, Iryna Semchuk, Oleksandr Horbach, Natalia Khranovska, Viktoriia Kosach, Petro Borysko, Serhii Koniev, Anne S. Ulrich, Sergii Afonin and Igor V. Komarov","doi":"10.1039/D5MD00075K","DOIUrl":"10.1039/D5MD00075K","url":null,"abstract":"<p >Three hallmarks of ICD (immunogenic cell death), release of adenosine triphosphate (ATP), release of high mobility group box 1 protein, and calreticulin exposure on the cell surface, were studied upon treatment of mammalian cells with small cyclic peptides, namely, the natural antibiotic gramicidin S (GS) and two photocontrolled GS analogues (LMB002 and LMB033). The analogues contained a photoisomerizable diarylethene fragment, and they exhibited different bioactivities in their “open” and “closed” photoisomeric forms. The data (obtained from cell cultures and spheroids) were collected in a concentration-dependent manner to assess cytotoxicity. Results showed that treatment with all peptides induced ICD at sub-IC<small>₅₀</small> and higher concentrations, indicating that GS and its derivatives have promising immunogenic potential. The “open” photoisomers of the photoswitchable GS analogues generated using visible light were as efficient as ICD inducers and the parent GS, while the UV-generated “closed” photoforms induced ICD only at higher concentrations. Herein, the cell specificity and time dependency of the observed effects are presented.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 8","pages":" 3456-3468"},"PeriodicalIF":3.597,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The development of a PET radiotracer for imaging alpha synuclein aggregates in Parkinson's disease†","authors":"Gui-Long Tian, Chia-Ju Hsieh, Dinahlee Saturnino Guarino, Thomas J. A. Graham, Zsofia Lengyel-Zhand, Alexander Schmitz, Wai Kit Chia, Anthony J. Young, John-Grey Crosby, Konstantinos Plakas, Tianyu Huang, Hao Jiang, Yanbo Yu, Catherine Hou, Hsiaoju Lee, E. James Petersson, Sam Giannakoulias, Jennifer O'Shea, Paul Kotzbauer, Zhude Tu, Chester A. Mathis and Robert H. Mach","doi":"10.1039/D5MD00057B","DOIUrl":"10.1039/D5MD00057B","url":null,"abstract":"<p > <strong>M503-1619</strong> was identified as a promising ligand for positron emission tomography (PET) imaging of α-synuclein (α-Syn) pathology in Parkinson's disease (PD). An exemplar for binding site 9 (residues GLY-86, ILE-88, PHE-94 and LYS-96) of α-Syn fibrils was generated. An <em>in silico</em> ultrahigh throughput screening campaign was conducted using a 42 million compound library. Secondary <em>in silico</em> methods followed by visual inspection were used to select 6 compounds as candidates for <em>in vitro</em> binding studies. <strong>M503-1619</strong> was found to have a high binding affinity (<em>K</em><small>_i</small> = 6.5 nM <em>versus</em> the site 9 radioligand [<small>³</small>H]BF-2846) to α-Syn fibrils and low affinity for beta amyloid (<em>K</em><small>_i</small> = 390 nM <em>versus</em> [<small>³</small>H]PiB) in competition binding assays. Saturation binding assays of <strong>[<small>³</small>H]M503-1619</strong> in human tissues confirmed its high affinity to α-Syn (PD tissue, <em>K</em><small>_D</small> = 2.5 nM; Alzheimer's disease tissue, <em>K</em><small>_D</small> = 37 nM; progressive supranuclear palsy tissue, <em>K</em><small>_D</small> = 55 nM). Autoradiography studies demonstrated a higher binding of this radioligand in PD brain sections than in multiple system atrophy brain sections. PET studies with <strong>[<small>¹¹</small>C]M503-1619</strong> showed high brain uptake and rapid washout (whole brain peak to 60 min ratio = 3.2) in non-human primates. The results of this study suggest that <strong>[<small>¹¹</small>C]M503-1619</strong> is a lead compound for radiotracer development imaging α-Syn with PET.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 6","pages":" 2743-2753"},"PeriodicalIF":3.597,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, characterization, and toxicity evaluation of ciprofloxacin–chloranilic acid charge transfer complexes: potential for anticancer applications","authors":"Mahmoud M. Ali, Muhammad Alaa Eldeen, Mohamed E. El Awady, Ahmed A. Hamed, Heba A. H. Abd Elhameed, Amira Awadalla, Mohamed Alshehri, Hassan M. Otifi, Dalal Sulaiman Alshaya, Eman Fayad, Dalal Nasser Binjawhar and Mohamed Ali","doi":"10.1039/D5MD00091B","DOIUrl":"10.1039/D5MD00091B","url":null,"abstract":"<p > <em>Background</em>: Ciprofloxacin (CIP), an FDA-approved antimicrobial agent, is commonly used to treat a variety of bacterial infections. Recent studies have highlighted its potential anticancer properties, prompting further investigation into its broader pharmacological effects. <em>Aim of the study</em>: This study synthesized new charge transfer complexes (CTCs) resulting from the chemical reaction between the ligand CIP and the π-acceptor chloranilic acid (H<small>₂</small>CA). <em>Method</em>: Spectroscopic techniques were utilized to characterize the newly formed CTC. The <em>in vitro</em> toxicity of this complex was assessed using the MTT assay on a human carcinoma cell line, and the LD<small>₅₀</small> of the compounds under examination was calculated. The impact of this synthetic complex on the liver and kidneys was evaluated using 30 white male albino rats divided into three groups of ten. Hematological and biochemical tests were carried out on blood samples, and liver tissues were collected for further analysis. The harvested organs underwent histological evaluation. <em>Results</em>: The results indicated that in a liquid state, CIP interacts strongly with the acceptor in a 1 : 1 molar ratio, resulting in a distinct color change that serves as the first evidence of CTC formation. Various chemical techniques as UV-visible, FT-IR, and <small>¹</small>H NMR spectroscopy, were employed to elucidate the structures generated in the solid state. <em>Conclusion</em>: The synthesized charge transfer complex was screened for its toxicity and anticancer activity.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 7","pages":" 3146-3157"},"PeriodicalIF":3.597,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiproliferative effects, mechanism of action and tumor reduction studies in a lung cancer xenograft mouse model of an organometallic gold(i) alkynyl complex†","authors":"Uttara Basu, Anna Wilsmann, Sebastian Türck, Henrik Hoffmeister, Matthias Schiedel, Gilles Gasser and Ingo Ott","doi":"10.1039/D4MD00964A","DOIUrl":"10.1039/D4MD00964A","url":null,"abstract":"<p >Organometallic complexes offer a wide range of properties like structural variety, reaction kinetics, tunable lipophilicity and alternate mechanisms of activation under physiological conditions compared to platinum chemotherapeutics and are thus being explored for their potential anticancer applications. In this regard, gold(<small>I</small>) organometallics hold a pivotal position for their ability to act on biological targets different from DNA (which is the primary target of platinum therapeutics), such as thioredoxin reductase. Here, we report on the stability, <em>in vitro</em> antiproliferative effects, protein binding, cellular uptake, mechanism of action, effects on mitochondrial respiration of cancer cells as well as <em>in vivo</em> tolerance, toxicity and tumor reduction in an A549 lung cancer xenograft mouse model of an organometallic gold(<small>I</small>) complex (<strong>1</strong>) bearing 4-ethynylanisole and triethylphosphane as ligands. The complex, which was stable in DMSO and reactive towards <em>N</em>-acetylcysteine, triggered strong antiproliferative effects in various cancer cell lines and had a protein binding of approximately 65% that reduced its generally efficient uptake into tumor cells. Antimetastatic properties were indicated for <strong>1</strong> in a scratch assay and strong inhibition of thioredoxin reductase (TrxR) was confirmed for the purified enzyme as well as in A549 lung cancer cells, which strongly overexpress TrxR. Real time monitoring of the oxygen consumption rate in multiple cancer cell lines, using the Seahorse Mito stress assay, demonstrated that mitochondrial respiration was severely disrupted, showing a significantly low oxygen consumption rate. Other respiratory parameters, such as proton efflux, spare respiratory capacity and maximal respiration, were also attenuated upon treatment with <strong>1</strong>. The complex was well tolerated <em>in vivo</em> in mice at a dose of 10 mg kg<small>⁻¹</small> and showed tumor reduction compared to the control group of animals in a lung cancer xenograft model of nude mice. In summary, complex <strong>1</strong> represents a novel organometallic anticancer drug candidate with a mechanism related to TrxR inhibition and mitochondrial respiration inhibition, showing efficient <em>in vivo</em> antitumor efficacy.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 6","pages":" 2663-2676"},"PeriodicalIF":3.597,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}