Medicinal Chemistry Research最新文献

{"title":"Nafithromycin (MIQNAF®): ultramodern lactone ketolide designed to treat community acquired bacterial pneumonia (CABP)","authors":"Satish Bhawsar,&nbsp;Ravikumar Tadiparthi,&nbsp;Abhijeet K. Kayastha,&nbsp;Prasad Dixit,&nbsp;Laxmikant Pavase,&nbsp;Amit Mishra,&nbsp;Vijay Chavan,&nbsp;Satish Birajdar,&nbsp;Mohammad Shaikh,&nbsp;Ravindra Yeole,&nbsp;Sachin Bhagwat,&nbsp;Mahesh Patel","doi":"10.1007/s00044-024-03281-5","DOIUrl":"10.1007/s00044-024-03281-5","url":null,"abstract":"<div><p>Community acquired bacterial pneumoniae (CABP) infections is the major cause of mortality and morbidity, especially in elderly patients. India accounts for 23% of global pneumonia burden with case fatality rates between 14 and 30%. There is an urgent unmet medical need for safe and effective antibiotic for CABP, due to lack of effective empirical therapy because of widespread resistance to β-lactams antibiotics. On other hand, fluoroquinolone antibiotics have poor tolerability, like hypersensitive reactions and associated disabilities. Hence, our objective was to find an antibiotic having broad coverage of multidrug resistance (MDR) pathogens including typical and atypical respiratory pathogens, with good lung penetration and safety features. Nafithromycin (MIQNAF^®) is a novel “lactone-ketolide” antibiotic developed by Wockhardt Ltd. for the treatment of CABP infections. Recently it has completed phase III clinical trials in India and NDA submitted to drug controller general of India (DCGI). Distinctive features of nafithromycin are ultra-short duration of therapy, oral dosing, high concentration build up in lung i.e. target organ and safety profile. Structurally, it features novel amidoxime core with 2-pyridine-1,3,4-thiadiazole biaryl tether separated with non-flexible four atom spacer having <i>cis</i> double bond and chiral methyl with (<i>S</i>)- configuration resulted in dual target interaction. The novel conformational arrangement interacts favorably with 23S rRNA and domain V of 50S ribosome subunit to elicit outstanding potency against gram-positive bacteria. The preclinical data provided strong scientific evidences for its effectiveness against difficult-to-treat respiratory tract infections (RTIs) caused by multidrug-resistant pathogens such as macrolide-resistant strains of <i>Streptococcus pneumoniae</i> and <i>Streptococcus pyogenes</i> as well as other important pathogens including <i>Haemophilus influenzae</i>. Upon successful phase I clinical findings, nafithromycin was granted Qualified Infectious Disease Product (QIDP) status by the US Food and Drug Administration (USFDA). Presently besides India specific phase III clinical study completion with partial funding support from Biotechnology Industry Research Assistance Council (BIRAC), it has successfully completed global phase II clinical development, including pharmacokinetic study (NCT02770404) and study for the treatment of community-acquired bacterial pneumonia (NCT02903836). In Europe it has completed single ascending dose (SAD) and multiple ascending dose (MAD) phase I pharmacokinetic studies. This mini review covers relevant published data on nafithromycin and its potential role in management of infections caused by gram-positive pathogens along with summary of different clinical trials conducted in United States, Europe and India.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 10","pages":"1715 - 1733"},"PeriodicalIF":2.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772105","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":"Facile access to novel furoyl-based amide retroisoster inhibitors of LuxR-regulated quorum sensing: conformation analysis and docking studies","authors":"Laurent Soulère,&nbsp;Yves Queneau","doi":"10.1007/s00044-024-03285-1","DOIUrl":"10.1007/s00044-024-03285-1","url":null,"abstract":"<div><p>A series of <i>N</i>-alkylfuran-2-carboxamide derivatives was easily prepared through direct acylation of diverse amines with 2-furoyl chloride. Using an <i>E. coli</i> reporter strain, all compounds were then examined as LuxR-regulated quorum sensing modulators for their agonistic or antagonistic activity. Compounds with a C8 or specially C6 alkyl chain with a comparable chain length with the natural ligand of LuxR were found to be antagonists with an IC₅₀ value of 25 µM. Competition experiments between the <i>N</i>-hexylfuran-2-carboxamide with the natural ligand indicate that the LuxR activity could be restored with high concentration of LuxR ligand. Conformational analysis, docking simulations and protein-ligand affinity prediction suggest that furan-2-carboxamide derivatives interact within the LuxR binding site <i>via</i> H-bonds of the C = O oxygen atom with Tyr62 OH and of the amide NH with Asp79 carboxylate, Tyr62 and Asp79 being two important conserved residues in the LuxR family. The binding mode also suggests that the absence of the hydrogen bond with Trp66, normally observed for the amide retroisoster analogs having the lactone instead of the furyl moiety, is not deleterious to the ability to interact and induce inhibition.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 10","pages":"1854 - 1860"},"PeriodicalIF":2.6,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141740020","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, in vitro activity, and molecular docking of caffeic acid and resveratrol derivatives against Alzheimer’s disease-related enzymes","authors":"Alberto Martínez","doi":"10.1007/s00044-024-03278-0","DOIUrl":"10.1007/s00044-024-03278-0","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is the most common form of dementia affecting about 40 million people around the world. The number of people living with this ailment is expected to triple in the next 50 years due to the aging population and the lack of any effective treatment. In this work we have synthesized a group of three hybrid caffeic acid and a resveratrol derivatives (<b>1-4</b>), and we have tested their ability to inhibit in vitro the enzymatic activity of the beta-site amyloid precursor protein cleaving protein enzyme 1 (BACE 1) and acetylcholinesterase (AChE). The inhibitory activity was compared to that of parent compounds caffeic acid and resveratrol, as well as related chlorogenic acid. Clinically tested LY2811376 and tacrine were used as positive controls. All three caffeic acid derivatives displayed better inhibitory activity than parent caffeic acid and chlorogenic acid. In particular, the in vitro IC₅₀ for compound <b>4</b> against BACE 1 fell in the nanomolar range (69 ± 5 nM), comparable or better than LY2811376 (173 ± 8 nM) which reached Phase I clinical trials against AD as a BACE 1 inhibitor. On the other hand, compound <b>3</b> showed a remarkable AChE inhibitory potency in the low micromolar range (1.93 ± 0.16 μM). Molecular docking was performed to gain valuable insights into the interactions between compounds <b>1-4</b> and the active sites of both BACE 1 and AChE. Calculated binding affinities generally correlated well with experimental in vitro inhibition. Experimental and molecular docking results validated the proposed drug design, since the most active compounds <b>3</b> and <b>4</b> established interactions with relevant amino acid residues of the BACE 1 and AChE active sites through the different pharmacophore features of the hybrid structures. Overall, the results presented in this work could potentially have important implications in the rational design of compounds with potential anti-AD properties.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 9","pages":"1681 - 1697"},"PeriodicalIF":2.6,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141740021","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":"Ultrasound-assisted synthesis of 4-thiazolidinone Schiff bases and their antioxidant, α-glucosidase, α-amylase inhibition, mode of inhibition and computational studies","authors":"Pule Seboletswe,&nbsp;Gobind Kumar,&nbsp;Lungisani Kubone,&nbsp;Kolawole Olofinsan,&nbsp;Almahi Idris,&nbsp;Md. Shahidul Islam,&nbsp;Parvesh Singh","doi":"10.1007/s00044-024-03268-2","DOIUrl":"10.1007/s00044-024-03268-2","url":null,"abstract":"<div><p>Diabetes mellitus (DM) has become a growing concern to global public health, being at the forefront of acute disorders and causes of mortality across the globe. Clinically approved drugs that are currently being used are faced with severe side effects, consequently necessitating the development of new drugs with no/fewer side effects and improved pharmacological potency. Herein, we report a rapid and efficient synthesis of thiazolidinone Schiff bases (<b>2a</b>-<b>2t)</b> from benzylidenehydrazines and thioglycolic acid under neat conditions through ultra-sonication. All the synthesized compounds were obtained in exceptional yields (89–95%) and confirmed by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, as well as High-resolution mass spectrometry (HRMS). The synthesized compounds were then evaluated for their antidiabetic activity through <i>α</i>-glucosidase and <i>α</i>-amylase inhibitory potentials and their antioxidant activity through Nitric Oxide (NO), 2,2′-diphenyl-1-picrylhydrazyl <b>(</b>DPPH), and Ferric reducing antioxidant power (FRAP) assays. Among them, <b>2q</b> (IC₅₀ = 96.63 μM) and <b>2h</b> (IC₅₀ = 125.27 μM) emerged as the most potent derivatives against α-amylase relative to reference drug acarbose (IC₅₀ = 131.63 µM), respectively. Antioxidant evaluation further revealed that the synthesized derivatives were excellent NO scavengers disclosing <b>2n</b> (IC₅₀ = 44.95 µM) as the most potent derivative. Moreover, in silico ADME calculations predicted these compounds to have excellent drug-like properties. Kinetic studies disclosed the mode of α-amylase inhibition as competitive while molecular docking studies of the most active derivatives performed into the binding active site of human pancreatic α-amylase enzyme deciphered their ligand-protein interactions that explicated their observed experimental potencies.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 9","pages":"1578 - 1597"},"PeriodicalIF":2.6,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-024-03268-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141829314","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}

{"title":"A novel class of indole derivatives: enhanced bioavailability, permeability, and antioxidant efficacy for thromboembolic disease therapy","authors":"S. Mandalapu, Shanshan Hou, Steffen Jockusch, Zhiying Shan, Lanrong Bi","doi":"10.1007/s00044-024-03277-1","DOIUrl":"https://doi.org/10.1007/s00044-024-03277-1","url":null,"abstract":"","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"13 7","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141646703","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":"Potential therapeutic effects of ester derivatives of Ribavirin against SARS-CoV-2","authors":"Aaminat Qureshi,&nbsp;Samina Bano","doi":"10.1007/s00044-024-03262-8","DOIUrl":"10.1007/s00044-024-03262-8","url":null,"abstract":"<div><p>Ribavirin (<b>1</b>) esters <b>4–36</b> have been synthesized and tested for their anti-inflammatory and anti-viral properties against SARS-CoV-2. The impaired host immune response known as cytokine release syndrome is one of the major causes of COVID-19 infection-related death. The current study aimed to assess compounds <b>4–36</b> against viral infection <i>in Vero</i> cells (viral titration, cytopathic effects, anti-viral efficacy, and results of treatment points) and anti-inflammatory activity against cytokines (IL-2, GM-CSF, IL-6, TNF-α, IFN-γ and IL-1β) were quantified at the protein level by using ELISA, oxidative burst assay, nitric oxide inhibition assay, anti-proliferative activity. Cytotoxicity of compounds was also determined. Compound <b>13</b> showed promising results against anti-inflammatory activity (100.80%, IC₅₀ = 0.40 ± 0.01 µM) and SARS-CoV-2 infection inhibition up to 80% (IC₅₀ = 1.42 ± 0.28). Nonetheless, further investigation is necessary to enhance and synthesize long-acting Ribavirin esters-based anti-inflammatory and SARS-CoV-2 medications based on the identified patterns.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 9","pages":"1554 - 1567"},"PeriodicalIF":2.6,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141609460","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":"ATP-hydrolyzing, DNA-damaging and cytotoxic activities of peptide-targeted cobalt(III) complex with diethylentriamine","authors":"Marat I. Kamalov,&nbsp;Andrey V. Nemtarev,&nbsp;Rezeda A. Ishkaeva,&nbsp;Kenana Dayob,&nbsp;Diana V. Salakhieva,&nbsp;Timur I. Abdullin","doi":"10.1007/s00044-024-03248-6","DOIUrl":"10.1007/s00044-024-03248-6","url":null,"abstract":"<div><p>Coordination complexes of cobalt represent a potential alternative to anticancer platinum-derived drugs owing to multiple activities and better toxicity profile. This work is aimed at generation of novel cobalt complexes based on peptide-conjugated diethylentriamine (Dien) ligand. Dien derivatives including SPPS-compliant Boc-protected N,N′-di(2-aminoethyl)glycine and its conjugate with RGD peptide derivative (compound <b>6</b>) were synthesized. Cobalt(III) complexes of Dien and <b>6</b> were obtained and characterized. Both complexes exhibited comparable ATP-depleting activity in solution and in PC-3 and OVCAR-4 cancer cells. The complex of <b>6</b> showed profoundly increased prooxidant, cytotoxic, and apoptotic in vitro effects compared to the non-targeted counterpart. Both complexes bound DNA and caused its significant damage in the presence of glutathione or hydrogen peroxide. These results provide an important background for development of bioactive cobalt complexes conjugated with biospecific oligopeptides.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 9","pages":"1541 - 1553"},"PeriodicalIF":2.6,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141609461","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":"Bexagliflozin: a comprehensive review of a recently approved SGLT2 inhibitor for the treatment of type 2 diabetes mellitus","authors":"Ryan L. Bassett, Giovanni Gallo, Kim-Phuong N. Le, Lucio R. Volino","doi":"10.1007/s00044-024-03274-4","DOIUrl":"https://doi.org/10.1007/s00044-024-03274-4","url":null,"abstract":"<p>Type 2 diabetes mellitus (T2DM) remains a major global health threat, claiming millions of lives annually. Despite recent advancements in managing T2DM, the need for innovative treatment options persists. Sodium-glucose cotransporter 2 (SGLT2) inhibition has proven to be an effective therapeutic strategy against T2DM, offering benefits in lowering hemoglobin A1c (HbA1c) and plasma glucose levels as well as treatment for patients with diabetes who develop chronic kidney disease (CKD). Bexagliflozin is a recently approved, orally administered SGLT2 inhibitor for treating T2DM and exhibits promise in combating CKD stages 3a and 3b. Structurally, bexagliflozin differs from other SGLT2 inhibitors in that it has a cyclopropyloxyethoxy group at the para position of the peripheral phenyl ring. This review article provides an overview of bexagliflozin’s discovery, mechanism of action, binding site interactions, metabolism, pharmacokinetics, and clinical applications. Emphasis is placed on the significant contribution of SGLT2 inhibitors, particularly bexagliflozin in glycemic control and treating associated comorbidities such as heart failure and chronic kidney disease in T2DM patients.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"62 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141587350","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":"Identification of potential natural product derivatives as CK2 inhibitors based on GA-MLR QSAR modeling, synthesis and biological evaluation","authors":"Yanan Xuan,&nbsp;Yue Zhou,&nbsp;Yue Yue,&nbsp;Na Zhang,&nbsp;Guohui Sun,&nbsp;Tengjiao Fan,&nbsp;Lijiao Zhao,&nbsp;Rugang Zhong","doi":"10.1007/s00044-024-03271-7","DOIUrl":"10.1007/s00044-024-03271-7","url":null,"abstract":"<div><p>Protein kinase CK2 is a validated target for cancer therapy. Many natural products have shown inhibitory activity against CK2 as potential anti-cancer drug candidates. A compatible quantitative structure-activity relationship (QSAR) model of natural products is necessary to identify the structural determinants related to their biological activities and provides valuable clues for the discovery of natural leads as anticancer drugs. In this study, genetic algorithm (GA) and multiple linear regression (MLR) methods, combined with preferred molecular descriptors, were employed to build QSAR models of CK2 natural product inhibitors. The best model, composed of eight molecular descriptors, yielded <i>Q</i>^<i>2</i>_<i>Loo</i> = 0.7914 and <i>R</i>^<i>2</i> = 0.8220 for the training set and <i>Q</i>^<i>2</i>_<i>ext</i> = 0.7921 and <i>R</i>^<i>2</i>_<i>ext</i> = 0.7998 for the test set, indicating the model’s robust reliability and high predictability. As a proof of concept, a true external test set, distinct from the training and test sets, was synthesized and tested in vitro to verify the predictive ability of this model. The predicted pIC₅₀ values of 13 compounds showed less than 30% relative error (including 10 compounds with relative errors less than 20%), further validating the predictive performance of this model. And compound M18, M24, and M26 were identified as potential CK2 inhibitors with the predicted pIC₅₀ values of 11.29, 8.79, and 12.03 respectively. Furthermore, the underlying structural mechanisms through which key molecular descriptors influenced their inhibitory activities against CK2 were elucidated. All these results provide valuable information for the discovery of CK2 inhibitors.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 9","pages":"1611 - 1624"},"PeriodicalIF":2.6,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141567687","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 anti-leishmanial activities of uniflorol analogues","authors":"Paula da Silva Cardoso,&nbsp;Luana Budny Niero,&nbsp;Tiago Elias Allievi Frizon,&nbsp;Silvia DalBó,&nbsp;Anne Cécile Le Lamer,&nbsp;Nicolas Gouault,&nbsp;Patrícia de Aguiar Amaral,&nbsp;James W. Barlow","doi":"10.1007/s00044-024-03275-3","DOIUrl":"10.1007/s00044-024-03275-3","url":null,"abstract":"<div><p>Chromanones are a subset of the benzopyran family, and display diverse biological activities, both as natural products and synthetic derivatives. Among these, we selected the natural product uniflorol, a 4-chromanone with an α,β-unsaturated ketone side chain, as a lead compound due to its reported anti-leishmanial properties. We designed and synthesised four series of novel compounds, varying the substitution patterns around the benzopyran core, and evaluated the compounds for anti-leishmanial activity against amastigotes of <i>L. infantum</i>. We prepared and characterised 24 novel compounds; upon screening, 12 compounds demonstrated activity values of &lt;50 μM, with the most potent compound, <b>16d</b>, having an IC₅₀ of 7.29 μM. Activity was favoured in compounds bearing a phenylalkenyl motif, such as cinnamyl, styryl or a more lipophilic extension, and amide analogues retained activity. Uniflorol analogues display promise as novel architectures towards the development of potential anti-leishmanial agents.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 9","pages":"1657 - 1670"},"PeriodicalIF":2.6,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-024-03275-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141567688","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}