Bioorganic & Medicinal Chemistry Letters最新文献

{"title":"Discovery of N-Ts-3-benzylidene-indolin-2-imines as potent anti-colorectal cancer agents through suppression of the PI3K-AKT pathway","authors":"Chuan-Chuan Wang ,&nbsp;Ya-Jing Chen ,&nbsp;Zhi-Hao Wang ,&nbsp;Tao Zhou ,&nbsp;Yuqi Zhou ,&nbsp;Yi-Gao Li ,&nbsp;Ying Fan ,&nbsp;Qiwen Shi","doi":"10.1016/j.bmcl.2025.130437","DOIUrl":"10.1016/j.bmcl.2025.130437","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is among the most prevalent and aggressive malignancies, highlighting the urgent need for novel therapeutic agents. In this study, eleven <em>N</em>-Ts-3-benzylidene-indolin-2-imines <strong>3</strong> were synthesized and evaluated for their potential as novel anti-tumor agents. MTT assay in human colorectal, breast, lung, and liver cancer cell lines revealed that compound <strong>3h</strong>, bearing a methoxyl group, exhibited superior antiproliferative activity against SW620 cells, with an IC₅₀ value of 3.68 μM. The above compound was subsequently selected for further investigation of its anti-CRC activity. This compound effectively inhibited colony formation and induced G2/M arrest and apoptosis in SW620 cells. Western blot analysis further demonstrated that <strong>3h</strong> exerted its anti-tumor activity by blocking the PI3K-AKT signaling pathway. Moreover, potential binding modes of compound <strong>3h</strong> with several PI3K and AKT kinases were proposed using molecular docking studies. This is the first report to describe the anticancer activity of indolin-2-imines through the suppression of the PI3K-AKT pathway. Overall, our findings suggested that compound <strong>3h</strong> is a promising lead for the development of PI3K/AKT inhibitors and anti-CRC agents.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"130 ","pages":"Article 130437"},"PeriodicalIF":2.2,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285348","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 antiviral activity of thiazolyl hydrazones against dengue virus","authors":"Mohd Usman Mohd Siddique ,&nbsp;Deepak Shilkar ,&nbsp;Vasavi Garisetti ,&nbsp;Sheikh Murtuja ,&nbsp;Suzanne Kaptein ,&nbsp;Pieter Leyssen ,&nbsp;Johan Neyts ,&nbsp;Vinay N. Basavanakatti ,&nbsp;Subodh Mondal ,&nbsp;Susanta Kumar Mondal ,&nbsp;Gayathri Dasararaju ,&nbsp;Velmurugan Devadasan ,&nbsp;Barij Nayan Sinha ,&nbsp;Venkatesan Jayaprakash","doi":"10.1016/j.bmcl.2025.130436","DOIUrl":"10.1016/j.bmcl.2025.130436","url":null,"abstract":"<div><div>Our group has previously reported on (E)-4-(1-(2-(5-(4-chlorophenyl)thiazol-2-yl)hydrazono)ethyl)phenol (<strong>3a</strong>) as an antiviral agent against DENV with an EC₅₀ of 1.32 μM. In this study, we present the X-ray crystallographic structure and <em>in vitro</em> ADME profile of compound <strong>3a</strong>. Additionally, to optimize <strong>3a</strong>, we synthesized four derivatives (<strong>3b</strong>-<strong>3e</strong>) using an active analogue approach. The newly synthesized and characterized compounds were screened for antiviral activity against DENV <em>via</em> a virus reduction assay (RT-qPCR). Among them, compound <strong>3c</strong> emerged as the most potent, with an EC₅₀ of 0.01 μM and a selectivity index (SI) of 200. This compound was found to be 132 times more potent than <strong>3a</strong>, although its toxicity was 63 times higher than that of <strong>3a</strong>. Despite this, its selectivity index was twofold higher than that of compound <strong>3a</strong>. <em>In vitro</em> permeability and metabolic stability studies showed that compound <strong>3a</strong> exhibited permeability issues but demonstrated metabolic stability in both rat and human liver microsomes. <em>In vivo</em> pharmacokinetic studies in male rats revealed a bioavailability (F) of 6 % and a half-life (T_1/2) of 1.75 h for compound <strong>3a</strong>. The <em>in vivo</em> pharmacokinetic results for compound <strong>3c</strong> suggest that it may require an appropriate formulation strategy to enhance its pharmacokinetic parameters.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"130 ","pages":"Article 130436"},"PeriodicalIF":2.2,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278552","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 antitumor activity study of novel oleanolic acid structural derivatives targeting c-Kit","authors":"Xuan Zhou,&nbsp;Junjiao Ma,&nbsp;Liangfeng Zhang,&nbsp;Zibo Zhao,&nbsp;Ziwen Xu,&nbsp;Yanqiu Meng","doi":"10.1016/j.bmcl.2025.130433","DOIUrl":"10.1016/j.bmcl.2025.130433","url":null,"abstract":"<div><div>Oleanolic acid (OA) is a pentacyclic triterpenoid, which inhibits tumor cell proliferation. In this study, OA was selected as the lead compound, and computer-aided drug design was used to develop novel derivatives. Structural modifications were made at the C-1, C-2, C-3, and C-28 positions based on the previously established structure–activity relationship. This led to the synthesis of two classes of OA derivatives with high predicted binding affinity to the c-Kit receptor (2-anilino) ethyl 1-ene-3-oxooleanolic acid esters (<strong>I</strong>_{<strong>1</strong>}–<strong>I</strong>_{<strong>14</strong>}) and 1-ene-3-(<em>E</em>)-oxime-oleanolic acid esters (<strong>II</strong>_{<strong>1</strong>}–<strong>II</strong>_{<strong>11</strong>}). MTT assays revealed that these compounds exhibited significant inhibitory activity against HepG-2 and MCF-7 cell lines, with compounds <strong>I</strong>_{<strong>9</strong>} and <strong>II</strong>_{<strong>9</strong>} showing IC₅₀ values comparable to those of the reference drugs gefitinib and sorafenib. Additionally, Western blot analysis revealed that treatment with compound <strong>I</strong>_{<strong>9</strong>} led to a concentration-dependent downregulation of c-Kit expression, indicating that its antitumor activity may be mediated, at least in part, through inhibition of c-Kit signaling.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"130 ","pages":"Article 130433"},"PeriodicalIF":2.2,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278528","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":"Repurposed ciprofloxacin derivatives as potent autophagic-type anticancer agents","authors":"Nilu Vijay Gone ,&nbsp;Tanisha Sharma ,&nbsp;Rakesh Joshi ,&nbsp;Akshita Upreti ,&nbsp;Manas Santra ,&nbsp;Gangadhar J. Sanjayan","doi":"10.1016/j.bmcl.2025.130432","DOIUrl":"10.1016/j.bmcl.2025.130432","url":null,"abstract":"<div><div>Drug repurposing - also known as drug repositioning is a proven strategy for identifying new therapeutic uses for existing and pre-approved drugs with considerable success in recent years. Herein, we report the discovery of a novel class of ciprofloxacin-amino acid conjugates that are dynamically potent against different cancer cell lines. Some of the molecules reported herein displayed a strong anti-proliferative effect on MCF-7 (IC₅₀: 6 μM). The most active anti-proliferative molecule of this series <strong>7a</strong> suppressed the proliferation of HCT116, A549, and MDA-MB-231 cancer cell lines. Furthermore, we established that the treatment with <strong>7a</strong> leads to DNA damage-mediated autophagic cell death in cancer cells. Our findings suggest that appropriate derivatization of the ciprofloxacin drug can yield promising anti-cancer compounds in easy synthetic operations.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"130 ","pages":"Article 130432"},"PeriodicalIF":2.2,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278587","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 biological activity study of pH-responsive amphipathic antimicrobial peptide hydrogels","authors":"Libo Yuan ,&nbsp;Liyang Tang ,&nbsp;Lige Liu ,&nbsp;Yu Zhang ,&nbsp;Yuan Fang ,&nbsp;Kui Lu","doi":"10.1016/j.bmcl.2025.130435","DOIUrl":"10.1016/j.bmcl.2025.130435","url":null,"abstract":"<div><div>This study designed and synthesized amphipathic peptides(KF-series peptides) containing lysine K and phenylalanine F to investigate the effects of positive charges on both antibacterial efficacy and gelation performance. Experimental observations via SEM demonstrated that peptides are capable of disrupting the bacterial membrane. Spectroscopic analysis indicates that with the number of positive charges increases, the binding mode of KF-series peptides with DNA transitions from intercalative binding and electrostatic binding to groove binding coupled with electrostatic binding. Antimicrobial experiments demonstrated that the antibacterial efficacy of KF-series peptides progressively enhanced with increasing positive charge quantity, while exhibiting broad-spectrum antimicrobial activity against palmar bacteria. Further structural analysis on KF-1 and KF-2 peptides were demonstrated by inducing their self-assembly into hydrogels in high pH value. TEM results showed distinct microscopic morphologies of the KF-1 peptide under varying pH conditions. Rheological data indicated that KF-1 exhibited superior rheological performance. Although increasing positive charges enhanced the antimicrobial activity of the peptides, this improvement compromised the stability of the gel structure. Therefore, maintaining an appropriate ratio between basic amino acids and nonpolar amino acids is crucial for designing peptides with both antimicrobial capability and gelation capability. This study provides novel insights into the design of innovative dual-functional antimicrobial peptide hydrogels.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"130 ","pages":"Article 130435"},"PeriodicalIF":2.2,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278559","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":"Targeted design, synthesis, molecular simulation, ADME-T and in-vitro anticancer assessment of phenyl-substituted-thioxo-tetrahydro-pyrimidin-benzenesulfonamide derivatives as potential BRAFV600E/WT inhibitors","authors":"Ankit Kumar Singh ,&nbsp;Vineet Prajapati ,&nbsp;Adarsh Kumar ,&nbsp;Vimlendu Kumar Sah ,&nbsp;Prateek Pathak ,&nbsp;Mashooq A. Bhat ,&nbsp;Mohamed A. Al-Omar ,&nbsp;Amita Verma ,&nbsp;Pradeep Kumar","doi":"10.1016/j.bmcl.2025.130431","DOIUrl":"10.1016/j.bmcl.2025.130431","url":null,"abstract":"<div><div>BRAF is one of the most commonly mutated oncogenes in human cancers, with more than 90 % of mutations occurring at codon 600. Among these, BRAF^V600E is the most prevalent, accounting for nearly 90 % of all BRAF codon 600 mutations, while the less frequent variants are collectively referred to as BRAF^V600WT. BRAF mutations are reported across several cancers, with the highest frequency in malignant melanoma (70–90 %).</div><div>To target these mutations, a series of phenyl-substituted thioxo-tetrahydro-pyrimidine-benzenesulfonamide hybrids in the [αC-OUT/DFG-IN] conformation were designed. Fourteen derivatives were synthesized through multistep reactions and evaluated for ADME-T properties and <em>in silico</em> binding affinities using molecular docking, further validated by molecular dynamics (MD) simulations of the top-ranked compound. In addition, cytotoxic activity against melanoma cell lines was assessed, followed by kinase inhibition studies on the most potent derivatives against BRAF^V600E/WT.</div><div>All compounds exhibited favorable ADME-T and drug-like properties. Among them, <strong>AV05</strong> demonstrated the highest binding affinity (−8.013 kcal/mol) and potent cytotoxic activity (IC₅₀ = 1.25 ± 0.57 μM), with BRAF^V600E inhibition (0.89 ± 0.78 μM) comparable to <strong>sorafenib</strong> (−6.189 kcal/mol; IC₅₀ = 0.90 ± 0.21 μM; inhibition = 0.10 ± 0.01 μM). In contrast, <strong>AV01</strong> showed the strongest affinity for BRAF^V600WT (−4.954 kcal/mol) and kinase inhibition (0.93 ± 0.28 μM), relative to <strong>sorafenib</strong> (−12.241 kcal/mol; inhibition = 0.16 ± 0.01 μM). Collectively, computational and biological evaluations revealed that the synthesized hybrids exhibited higher selectivity and potency toward BRAF^V600E than BRAF^V600WT, with <strong>AV05</strong> emerging as the most promising compound.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"130 ","pages":"Article 130431"},"PeriodicalIF":2.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273287","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 and synthesis of guanidino derivatives of benzoate esters as SIRT6 inhibitors","authors":"Yongzhi Ma ,&nbsp;Minni Ding ,&nbsp;Kewang Yu ,&nbsp;Siyu Wang ,&nbsp;Siyuan Wang ,&nbsp;Hao Cao ,&nbsp;Huiming Hua ,&nbsp;Dahong Li","doi":"10.1016/j.bmcl.2025.130430","DOIUrl":"10.1016/j.bmcl.2025.130430","url":null,"abstract":"<div><div>SIRT6 is a key member of the Sirtuin family and plays a crucial role in regulating cellular metabolism, maintaining genomic stability, and influencing the aging process. SIRT6 inhibitors have garnered significant attention due to their potential therapeutic value in treating cancer, inflammation, and metabolic diseases. In this study, a high-throughput virtual screening approach, combined with FLUOR DE LYS detection, was employed to identify the guanidino benzoate ester compound <strong>Hit 13</strong>, which exhibits SIRT6 inhibitory activity. Subsequent structural optimization yielded a series of analogs. Among these, compounds <strong>15</strong>, <strong>25</strong>, and <strong>27</strong> demonstrated SIRT6 inhibitory activity and selectivity. Combination therapy, an emerging strategy in cancer treatment, has demonstrated promising efficacy. The combination of SIRT6 inhibitors with chemotherapy drugs can produce synergistic cytotoxic effects, reverse drug resistance, and has the potential to reduce chemotherapy doses while mitigating side effects. When compound <strong>15</strong> or <strong>25</strong> was combined with chemotherapy agents, they significantly enhanced the anti-proliferative effects of these drugs on tumor cells. This sensitization effect was particularly pronounced with doxorubicin, which reduced its IC₅₀ value against MCF-7 cells from 11 μM to 4 μM. Compounds <strong>15</strong> and <strong>25</strong> may serve as promising lead compounds for drug development targeting SIRT6.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"130 ","pages":"Article 130430"},"PeriodicalIF":2.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249077","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":"In vitro comparison of the glycosidase inhibitory profile of isoiminosugars with their 1- and 5a-modified derivatives","authors":"Solveig Auranaune Markussen ,&nbsp;Óscar López ,&nbsp;Emil Lindbäck","doi":"10.1016/j.bmcl.2025.130426","DOIUrl":"10.1016/j.bmcl.2025.130426","url":null,"abstract":"<div><div>Isoiminosugars are a group of glycomimetics known for being among the most potent glycosidase inhibitors, making them attractive as lead compounds in drug discovery. This review article summarizes how glycosidase inhibitory activities in <em>in vitro</em> assays are influenced by substituents attached to the 1- and 5a-positions of polyhydroxylated piperidine isoiminosugars, compared to their non-substituted parent compounds. Additionally, the review gives an overview of the glycosidase inhibitory properties of common iminosugars. It also discusses how these properties are affected when the nitrogen atom in iminosugars, which occupies the position of the endocyclic oxygen atom in monosaccharides, is relocated to the position of the anomeric carbon atom to form isoiminosugars.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"130 ","pages":"Article 130426"},"PeriodicalIF":2.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249047","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":"Privileged scaffold repurposed: the evolving role of quinolone derivatives in antiviral therapy","authors":"Hui Xu ,&nbsp;Baohu Li ,&nbsp;Kai Tang ,&nbsp;Jinfei Yang ,&nbsp;Peng Zhan","doi":"10.1016/j.bmcl.2025.130427","DOIUrl":"10.1016/j.bmcl.2025.130427","url":null,"abstract":"<div><div>Significant advancements have been made in the field of antiviral drug development; however, existing therapies still face considerable challenges regarding safety and efficacy. Moreover, with the frequent emergence of outbreaks caused by viruses such as SARS-CoV-2, monkeypox virus, and Chikungunya virus in recent years, there is an urgent need to develop novel antiviral drugs that are highly effective, low-toxic, and possess broad-spectrum activity against drug-resistant strains. Exploring antiviral agents from privileged structures has long been a tacit shortcut for researchers, and quinolone derivatives, as a class of privileged structures with diverse antiviral activities, have attracted extensive attention in recent years, providing a crucial material basis for the development of next-generation antiviral drugs. This review focuses on the discovery, mechanisms of action, potential clinical applications, and research progress of quinolone derivatives with typical structural characteristics or potent antiviral activity, aiming to provide insights for current and future antiviral drug research.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"130 ","pages":"Article 130427"},"PeriodicalIF":2.2,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237464","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 and validation of the first-in-class PROTACs for targeted degradation of the immune checkpoint LAG-3","authors":"Nelson García Vázquez ,&nbsp;Somaya A. Abdel-Rahman ,&nbsp;Hossam Nada ,&nbsp;Moustafa Gabr","doi":"10.1016/j.bmcl.2025.130428","DOIUrl":"10.1016/j.bmcl.2025.130428","url":null,"abstract":"<div><div>Lymphocyte activation gene-3 (LAG-3) is an inhibitory immune checkpoint receptor that plays a central role in T cell exhaustion and immune evasion in cancer. While monoclonal antibodies targeting LAG-3 have entered clinical development, small molecule approaches remain largely unexplored. Here, we report the design and validation of the first-in-class PROTACs for targeted degradation of LAG-3. In this study, we repurposed a LAG-3-binding small molecule identified through DNA-encoded library (DEL) screening as the targeting ligand for a series of CRL4^CRBN-based PROTACs designed with varied linker lengths. Western blot analysis in Raji-LAG3 cells demonstrated that <strong>LAG-3 PROTAC-1</strong> and <strong>LAG-3 PROTAC-3</strong> induce potent, dose-dependent degradation of LAG-3, with DC₅₀ values of 0.27 μM and 0.42 μM, respectively. Molecular docking and molecular dynamics (MD) simulations revealed the LAG-3 binding mode of designed PROTACs and provided structural insights into PROTAC-mediated ternary complex formation. Collectively, this work establishes a proof-of-concept for chemical degradation of LAG-3 for the first time and paves the way for novel immunotherapeutic strategies.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"130 ","pages":"Article 130428"},"PeriodicalIF":2.2,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237450","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}