Medicinal Chemistry Research最新文献

{"title":"A guide for asymmetric synthesis of morphine alkaloids","authors":"Hui Zhao,&nbsp;Yunfei Cheng","doi":"10.1007/s00044-024-03350-9","DOIUrl":"10.1007/s00044-024-03350-9","url":null,"abstract":"<div><p>A collection of structurally related natural compounds derived from Papaver somniferum, the opium poppy, are known as the morphine alkaloids. Many generations of synthetic chemists have been drawn to the synthesis of morphine and its derivatives owing to their extraordinarily complex molecular architecture and exceptional biological activity. This overview highlights recent advance in the asymmetric synthesis of morphine alkaloids, focusing on various strategies for introducing and controlling chirality, which will hasten the feasibility of commercial production of morphinan.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"319 - 339"},"PeriodicalIF":2.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925573","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 evaluation of benzimidazole derivatives with potent HDAC inhibitory activity","authors":"Jiantao Ping,&nbsp;Hongrui Chu,&nbsp;Yisheng Zhao,&nbsp;Chen Chen","doi":"10.1007/s00044-024-03349-2","DOIUrl":"10.1007/s00044-024-03349-2","url":null,"abstract":"<div><p>This study aims to design and synthesize novel benzimidazole histone deacetylase (HDAC) inhibitors to explore their potential applications in the treatment of cancer and other related diseases. By comparing the structures of our reported benzimidazole HDAC inhibitors, we designed a series of compounds accordingly. We then used experimentally verified their inhibitory activity against HDAC enzymes. The results showed that several of the newly synthesized compounds showed good HDAC inhibition and anti-proliferative activity. Therefore, we conclude that these novel HDAC inhibitors have potential as drug candidates for the treatment of cancer.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"445 - 454"},"PeriodicalIF":2.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925531","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":"Phytochemical constituents isolated from Silene popovii Schischk","authors":"Ugiloy Yu. Yusupova,&nbsp;Khayrulla M. Bobakulov,&nbsp;Alisher R. Khurramov,&nbsp;Vladimir N. Syrov,&nbsp;Feruza R. Egamova,&nbsp;Anas Karuth,&nbsp;Durbek A. Usmanov,&nbsp;Mohiuddin Quadir,&nbsp;Bakhtiyor Rasulev","doi":"10.1007/s00044-024-03345-6","DOIUrl":"10.1007/s00044-024-03345-6","url":null,"abstract":"<div><p>In this work, with the aim to find new and biologically active natural compounds, the chemical content of the apolar and polar extracts (aerial part) of <i>Silene popovii</i> has been investigated. The obtained extracts of <i>Silene popovii</i> Schischk were purified by column chromatography (CC), and four compounds were isolated: one of them is a new saponin compound—silepovin (<b>1</b>), as well as three known secondary metabolites, 2-deoxy-α-ecdysone (<b>2</b>), cauloside A (<b>3</b>) and 20-hydroxyecdysone 22-benzoate (<b>4</b>). The structural elucidation of isolated compounds was performed using the 1D and 2D NMR spectroscopy analyses and LC-MS analysis, and all four structures were confirmed. For the new compound <b>1</b>, an in vivo study of anti-inflammatory activity was conducted. The in vivo analysis has shown significant anti-inflammatory effects.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"423 - 431"},"PeriodicalIF":2.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925529","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":"Thiophene ring-opening reactions. Part VII: synthesis and antitumor, anti-inflammatory, and antioxidant properties of 1,3,4‒thiadiazoline‒6-sulfanylthiopyran-4(1H)-one hybrids","authors":"Shaima K. Alsawaleha,&nbsp;Jalal A. Zahra,&nbsp;Mustafa M. El-Abadelah,&nbsp;Violet Kasabri,&nbsp;Salim S. Sabri,&nbsp;Monther A. Khanfar","doi":"10.1007/s00044-024-03343-8","DOIUrl":"10.1007/s00044-024-03343-8","url":null,"abstract":"<div><p>The reaction of <i>N</i>′’(aryl)benzothiohydrazides with 2-chloro-6-((substituted)amino)-3-nitro-4-oxo-4H-thieno[2,3-b]thiopyran-5-carboxylate (<b>13</b>-<b>15</b>) under basic conditions (NEt₃) in acetonitrile proceeds via thiophene ring-opening processes and yields, upon addition of iodomethane, the respective 1,3,4-thiadiazoline-6-sulfanylthiopyran-4(1<i>H</i>)-one hybrids. The new compounds were characterized by HRMS and NMR spectral data and confirmed by single-crystal X-ray crystallography. The cytotoxicity affinities for compounds <b>10</b>-<b>17</b> were evaluated in cross-correlations with their anti-inflammation and radical scavenging capacities. Compound <b>13</b> exhibited the highest cytotoxic properties, with IC₅₀ values ranging from 160 nM in mammary T47D to less than 20.35 µM in colorectal CACO2 among 12 diverse cancer monolayers. Compound <b>17c</b> significantly reduced lung and mammary cancer cell viability, with anti-tumorigenesis IC₅₀ values of less than 10 µM. These new compounds have the potential to be further optimized into novel selective cytotoxic treatments.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"392 - 405"},"PeriodicalIF":2.6,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925483","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":"Review: Chemical and biological features of genus Paralemnalia soft corals","authors":"Radwa Taher Mohie el-dien,&nbsp;Basma Khalaf Mahmoud,&nbsp;Amgad I. M. Khedr,&nbsp;Mohamed Salah Kamel,&nbsp;Mostafa A. Fouad","doi":"10.1007/s00044-024-03340-x","DOIUrl":"10.1007/s00044-024-03340-x","url":null,"abstract":"<div><p>Marine soft corals are plentiful sources of a wide range of natural products. They include an extensive array of chemical scaffolds that could eventually be utilized to develop novel drugs for human diseases due to the extraordinary diversity and number of bioactive small molecules identified from these animals. Soft corals belonging to the <i>Paralemnalia</i> genus (order Alcyonacea) are widely distributed throughout the Red Sea, Indian Ocean, Southeast Asia, and the Pacific Ocean. Numerous chemical components have been isolated and identified, including mainly sesquiterpenes, diterpenes, steroids, and fatty acids. Some compounds have been shown to exhibit various biological activities such as anti-inflammatory, cytotoxic, neuroprotective, antibacterial, and antiviral properties. However, no reviews have been published focusing on this genus until now. Here in this review, we attempt to delve into the reported metabolites from genus <i>Paralemnalia</i> according to the produced species, their chemical structures, and their biological potential.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"301 - 318"},"PeriodicalIF":2.6,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925775","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":"Evaluation of cholinesterase enzyme inhibitory potential of dipterocarpol derivatives","authors":"Irina E. Smirnova,&nbsp;Oxana B. Kazakova,&nbsp;Niels V. Heise,&nbsp;René Csuk","doi":"10.1007/s00044-024-03351-8","DOIUrl":"10.1007/s00044-024-03351-8","url":null,"abstract":"<div><p>Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) - are depression and neurodegenerative diseases that target enzymes, including Alzheimer’s disease (AD). With the goal of searching for cholinesterase enzyme inhibitors, a series of four new and twelve previously modified at C2/С2,С21 (arylidenes) and C3 (acylates) positions of dipterocarpol compounds were evaluated for acetylcholinesterase (from electric eel) and butyrylcholinesterase (from equine serum) inhibitory activity. As a result, dammaranes with 3<i>β</i>-<i>O</i>-(2-furoyl)- <b>2</b>, 2-(<i>p</i>-nitro-benzylidene)- <b>7</b>, and 2,21-<i>bis-</i>(<i>p</i>-carbonylbenzylidene)- <b>17</b> fragments exhibited a pronounced activity with 79.0, 68.8 and 75.2% inhibition of AChE, but were less active for BChE. The structure-activity relationship indicated that the type of substituents in the arylidene or ester moiety and the structure of the side chain of dammarane scaffold play an important role in the inhibition of AChE. Extra experiments showed them as mixed-type inhibitors with K_i 5.99 (for <b>2</b>), 2.43 (for <b>7</b>) and 0.51 µM (for <b>17</b>). Molecular docking studies showed that compounds <b>2</b>, <b>7</b>, and <b>17</b> have the highest binding scores −8.4, −8.9, and −8.7 kcal/mol, respectively. There are revealed key interactions and confirmed successful placement of the compounds <b>2</b>, <b>7</b>, and <b>17</b> in the active site of AChE, that elucidate these inhibitory effects.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"455 - 465"},"PeriodicalIF":2.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925744","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":"Monoamine oxidase inhibition by thiazole derivatives substituted with the benzenesulfonamide moiety","authors":"Anton Shetnev,&nbsp;Julia Efimova,&nbsp;Olga Gasilina,&nbsp;Eugenia Shabalina,&nbsp;Sergey Baykov,&nbsp;Dmitry Lifanov,&nbsp;Elena Petersen,&nbsp;Mikhail Korsakov,&nbsp;Anél Petzer,&nbsp;Jacobus P. Petzer","doi":"10.1007/s00044-024-03346-5","DOIUrl":"10.1007/s00044-024-03346-5","url":null,"abstract":"<div><p>Based on a report that 1,3,4-oxadiazol-2-ylbenzenesulfonamides act as inhibitors of monoamine oxidase B (MAO-B), the present study explored the effect of replacing the 1,3,4-oxadiazole moiety with a 1,3-thiazole heterocycle. A series of 23 primary sulfonamides were synthesized and evaluated as in vitro inhibitors of the human MAOs. The results showed that the 1,3-thiazolylbenzenesulfonamides were specific inhibitors of MAO-B with the most potent MAO-B inhibitor presenting with an IC₅₀ value of 0.103 µM (<b>3j</b>). Potent MAO-B inhibition was obtained with the substitution of the sulfonamide on the <i>meta</i> position of the phenyl rather than the <i>para</i> position. This study concluded that 1,3-thiazolylbenzenesulfonamides may serve as lead MAO inhibitors for the development of new treatments for disease states such as Parkinson’s disease.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"357 - 366"},"PeriodicalIF":2.6,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925572","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 novel tubulin polymerization inhibitors: design, synthesis, LC/MS cellular permeability, in silico studies, and in vitro assessment","authors":"Iman A. Y. Ghannam,&nbsp;Islam H. Ali,&nbsp;Rasha Z. Batran,&nbsp;Mahmoud T. Abo-elfadl,&nbsp;Rasha M. Allam,&nbsp;Ibrahim M. Ibrahim,&nbsp;Faten Farouk","doi":"10.1007/s00044-024-03327-8","DOIUrl":"10.1007/s00044-024-03327-8","url":null,"abstract":"<div><p>In this study, chalcones <b>5</b>, and <b>6</b> and pyrazolines <b>7</b>, and <b>8</b> were designed and synthesized as combrestatin A-4 (CA-4) analogues. The anticancer effect of the synthesized compounds <b>5-8</b> was assessed against a panel of cancer cell lines at 10 µM. Results revealed that the 3-benzyloxy chalcone <b>5</b> exhibited the highest GI % (81.43%) against all the cancer cell lines, and recorded the highest anticancer activity against HuH-7 liver cancer cell line (IC₅₀ = 5.59 μM). The effect of <b>5-8</b> on the microtubules network was visualized via immunofluroescence detection. The 3-benzyloxy chalcone <b>5</b>, and the 4-phenethyl chalcone <b>6</b> revealed microtubules destabilizing effects as CA-4, however, the pyrazolines <b>7</b>, and <b>8</b> showed microtubules stabilizing effects similar to that of paclitaxel. Moreover, it caused cell cycle arrest at G2/M phases as well as early and late apoptosis and necrosis induction in HuH-7 cells as recorded by flow cytometry. The ADME properties of the synthesized compounds <b>5-8</b> were investigated and their in vitro cellular permeability was also determined. The 3-benzyloxy chalcone <b>5</b> exhibited acceptable drug likeness properties and passed the Lipinski, Ghose, Veber and Egan rules filters, and revealed a good cellular permeability (41%) according to the LC-MS/MS permeability assay. Finally, molecular docking and dynamic studies were performed to investigate the binding modes of <b>5-8</b>. It was revealed that the 3-benzyloxy chalcone <b>5</b> exhibit a stable binding to the tubulin via multiple interactions with the key amino acids at the colchicine binding site.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>Chalcone <b>5</b> revealed mean GI₅₀ values 1.59–25.10 µM and a microtubules destabilizing agent.</p></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 1","pages":"183 - 204"},"PeriodicalIF":2.6,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912977","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":"Triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl nucleoside analogues. Synthesis, cytotoxicity and antimicrobial activity","authors":"Olga V. Andreeva,&nbsp;Alexandra D. Voloshina,&nbsp;Anna P. Lyubina,&nbsp;Bulat F. Garifullin,&nbsp;Anastasiia S. Sapunova,&nbsp;Syumbelya K. Amerhanova,&nbsp;Irina Yu. Strobykina,&nbsp;Mayya G. Belenok,&nbsp;Olga B. Babaeva,&nbsp;Vasily M. Babaev,&nbsp;Leysan R. Khabibulina,&nbsp;Liliya F. Saifina,&nbsp;Vyacheslav E. Semenov,&nbsp;Vladimir E. Kataev","doi":"10.1007/s00044-024-03339-4","DOIUrl":"10.1007/s00044-024-03339-4","url":null,"abstract":"<div><p>A series of new triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl nucleoside analogues were synthesised by coupling with 8-bromooctyl or 10-bromodecyl triphenylphosphonium bromide and evaluated in vitro for cytotoxicity against human cancer and normal cells and antimicrobial activity against Gram-positive cells, including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), Gram-negative bacteria and pathogenic yeasts. In these TPP conjugates, the TPP cation was attached via an octyl or decyl linker to the N3 atom of the heterocyclic fragment (uracil, thymine, 6-methyluracil, quinazoline-2,4-dione) and its N1 atom was attached via a methyl or butyl linker with a 1,2,3-triazolylribofuranosyl moiety. Lead compounds possessing a decyl linker between the heterocyclic fragment and the TPP cation showed high cytotoxicity against HuTu-80 cancer cells (IC₅₀ = 0.5 μM) with a selectivity index &gt;10. The lead compounds were found to induce apoptosis in HuTu-80 cancer cells via the mitochondrial pathway and to arrest the cell cycle of HuTu-80 cells in the G1 phase. Molecular docking modelling indicates that the lead compounds bind to the active site (BH3 domain) of the anti-apoptotic protein Bcl-2. Lead compounds with high anticancer specificity were also shown to be very active against <i>S. aureus</i> (MIC and MIC are 0.25–0.5 μM) and good efficacy against MRSA strains (MIC and MIC are 7.8–15.6 μM). In relation to bacteria, the lead compounds have a membranotropic effect due to a significant decrease in the potential of the cytoplasmic membrane.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"367 - 391"},"PeriodicalIF":2.6,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925523","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 aminothiazole-benzazole based amide: antiproliferative, antimigration activity and molecular docking studies","authors":"Gülnur Arslan Karahan,&nbsp;Yalçın Erzurumlu,&nbsp;Muhammed Tilahun Muhammed,&nbsp;Azime Berna Özçelik","doi":"10.1007/s00044-024-03344-7","DOIUrl":"10.1007/s00044-024-03344-7","url":null,"abstract":"<div><p>In this study, we synthesized a series of amide-functionalized aminothiazole-benzazole analogs for potential application in cancer treatment. The chemical structures of these compounds were confirmed using proton nuclear magnetic resonance (¹H NMR), carbon-13 nuclear magnetic resonance (¹³C NMR) spectroscopy, and high-resolution mass spectrometry (HRMS). We evaluated the cytotoxicity of these compounds against breast cancer cells (MCF-7) and lung adenocarcinoma cells (A549). Notably, Compound 6b demonstrated significant cytotoxicity, with IC₅₀ values of 17.2 ± 1.9 μM for MCF-7 cells and 19.0 ± 3.2 μM for A549 cells. Furthermore, we assessed the antimigration properties of all synthesized compounds, observing promising antiproliferative effects in both MCF-7 and A549 cells. Compound 6b exhibited a significant antimigration effect, achieving a 50.2 ± 4.7% wound healing rate in MCF-7 cells. In addition, we examined the impact of these compounds on key apoptotic proteins, including Caspase-7, PARP-1, BAX, and Bcl-2, which are critical in the regulation of programmed cell death. The binding potentials of the active compounds to BAX and Bcl-2 were also supported by docking. Results that consolidate the in vitro study were obtained from the in silico analysis. Our results suggest that these amide-functionalized aminothiazole-benzazole analogs exhibit potential as anticancer agents and merit further investigation to elucidate their mechanisms of action and therapeutic potential.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>The synthesis of novel aminothiazole-benzazole-based amide derivatives as potential anticancer agents has been reported. These compounds were evaluated for their cytotoxic activity against MCF-7 and A549 cancer cell lines, exhibiting IC₅₀ values ranging from 17.2 to 80.6 μM. Furthermore, the cytotoxic compounds demonstrated significant antimigration effects and induced apoptosis in both MCF-7 and A549 cell lines. Additionally, the results confirming the in vitro study were supported by in silico analysis.</p></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"406 - 422"},"PeriodicalIF":2.6,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925474","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}