Medicinal Chemistry Research最新文献

{"title":"Naturally occurring plant-derived sulfonated and sulfated saponins from 1983 to 2024","authors":"Bienvenu Tsakem,&nbsp;Shoeshoe Mokhele,&nbsp;Lerato Mosima,&nbsp;Madan Poka,&nbsp;Patrick Hulisani Demana,&nbsp;Rémy Bertrand Teponno,&nbsp;Xavier Siwe Noundou","doi":"10.1007/s00044-025-03412-6","DOIUrl":"10.1007/s00044-025-03412-6","url":null,"abstract":"<div><p>A substantial number of molecules have been already characterized from various organisms, such as plants, fungi, bacteria, and other animals; but just few have been already subjected to pharmacological assays. This is one of the reasons why reviewing previous studies will direct future investigations. The continuous chemical investigations of medicinal plants have been leading to a plethora of saponins. Some of these compounds carry one or more sulfonyl or sulfate groups. Such association rarely occurs in the plant kingdom. Till now, no report has summarized these sulfonated saponins isolated from medicinal plants. There is still a gap between the sulfonyl function and biological activities of these saponins. The present review encompasses the naturally occurring saponins containing the sulfonyl group either on the sapogenin or on the sugar moiety. The biosynthetic routes, their spectroscopic characteristics to shed more light on future structure elucidation and their biological activities are reported. It resulted that 141 saponins associating SO₃H or SO₃^- groups were reported from medicinal plants largely distributed within Zygophyllaceae and Asparagaceae families. Some of these compounds exhibited interesting biological activities including anticancer, antibacterial, anti-inflammatory and antiviral. It emerges from this review that many sulfonated saponins have been characterized, but just a few have been subjected to biological studies. The mechanism of action of these compounds remains understudied and further investigations need to be undertaken to understand how they act. This review covers reported data from 1983–2024.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1212 - 1236"},"PeriodicalIF":2.6,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03412-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125682","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":"Acetylcholinesterase Inhibitors from Carbamate and Benzo-fused Heterocyclic Scaffolds: Promising Therapeutics for Alzheimer’s Disease","authors":"Amarjith Thiyyar Kandy,&nbsp;Raghul Venkatesan,&nbsp;Devadharuna Mohan,&nbsp;Sajeeth Chadapullykolumbu Ismail,&nbsp;Srikanth Jupudi,&nbsp;Divakar Selvaraj","doi":"10.1007/s00044-025-03410-8","DOIUrl":"10.1007/s00044-025-03410-8","url":null,"abstract":"<div><p>Alzheimer’s disease is the most prevalent type of dementia, characterized by a progressive loss of memory and neurodegeneration that hinders a patient’s ability to perform daily tasks. This paper explores the potential of acetylcholinesterase inhibitors derived from carbamate and benzo-fused heterocyclic scaffolds as potential therapeutics for Alzheimer’s disease. Inhibiting acetylcholinesterase is crucial for enhancing cognitive function in Alzheimer’s patients. The findings indicate that novel compounds featuring the mentioned scaffolds exhibit promising acetylcholinesterase inhibitory efficacy. Several of these compounds display superior half-maximal inhibitory concentration values against acetylcholinesterase compared to FDA-approved acetylcholinesterase inhibitors. The review emphasizes the importance of these compounds in addressing the cholinergic deficits associated with Alzheimer’s disease, where the loss of cholinergic neurons results in reduced acetylcholine levels in the synaptic cleft. Benzimidazole-based thiazole derivatives have demonstrated remarkable inhibitory capabilities against cholinesterase enzymes, with some compounds showing half-maximal inhibitory concentration values as low as 0.10 µM. The review highlights the effectiveness of benzofuran, benzoxazole, indole, indolinone, and coumarin derivatives in inhibiting acetylcholinesterase and providing neuroprotection, making them promising candidates for treating Alzheimer’s disease. Additionally, the review emphasizes the necessity for further research into the mechanisms of action of these substances and their effects on cognitive performance in clinical settings to enhance the quality of life for Alzheimer’s patients. Overall, this work contributes to the ongoing search for effective treatments for Alzheimer’s, stressing the importance of discovering new chemical entities capable of improving neurotransmission and cognitive function.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1200 - 1211"},"PeriodicalIF":2.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125612","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":"Ferrocene-based compounds: promising anticancer and antimalarial agents in modern therapeutics","authors":"Anchal Sharma,&nbsp;Rupali Rana,&nbsp;Nitish Kumar,&nbsp;Harmandeep kaur gulati,&nbsp; Jyoti,&nbsp;Aanchal Khanna,&nbsp;Sofia Sharma,&nbsp; Pooja,&nbsp;Jatinder Vir Singh,&nbsp;Preet Mohinder Singh Bedi","doi":"10.1007/s00044-025-03408-2","DOIUrl":"10.1007/s00044-025-03408-2","url":null,"abstract":"<div><p>Ferrocene, owing to its inherent stability, favourable redox characteristics, and low toxicity, has emerged as a significant structural motif in the field of bioorganometallic chemistry. Two prominent examples of ferrocene’s impact on medicinal chemistry are ferroquine and ferrocifen, both demonstrating remarkable antimalarial and anticancer activities. The enhanced therapeutic properties observed in these drug candidates underscore the profound influence ferrocene can exert on the molecular and biological behaviour of bioactive compounds. This Perspective delves into the scope and limitations of incorporating ferrocene into organic molecules and natural products, examining how such modifications affect their mechanisms of action and overall biological activities. A detailed discussion is provided on the role of ferrocene derivatization in modulating the anticancer, antimalarial, and antimicrobial properties of diverse bioactive moieties. The ultimate goal is to provide insights that contribute to the design and development of safer and more effective ferrocene-based drugs and focusing on their potential to address the critical unmet needs in cancer and malaria treatment.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1177 - 1199"},"PeriodicalIF":2.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125559","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":"Discovery of novel pterostilbene/biphenyl tethered 5-FU based conjugates targeting colorectal cancer: synthesis, cytotoxic and ADMET modeling studies","authors":"Rubén Becerra-Quintana,&nbsp;Angie Herrera-Ramírez,&nbsp;Andrés F. Yepes,&nbsp;Laura Cadavid-Arango,&nbsp;Wilson Cardona-Galeano","doi":"10.1007/s00044-025-03401-9","DOIUrl":"10.1007/s00044-025-03401-9","url":null,"abstract":"<div><p>A new series of conjugates linking 5-FU with parts of pterostilbene and biphenyl were designed, and synthesized, besides, their biological activity was assessed against human colorectal adenocarcinoma cells (SW480) and the non-malignant cell line NCM460. Novel conjugates were first screened to establish the potential at 100 µM single dose, finding two active compounds <b>5e</b> and <b>5g</b> that caused more than 70% inhibition. In addition, in the seven-dose screening it was observed that, although both compounds were more active than the starting molecule <b>3</b>, only compound <b>5e</b> was more selective toward cancer cells than the drug 5-fluorouracil (5-FU). A theoretical examination of pharmacokinetics, toxicological, and drug-like characteristics indicates that the most promising hybrid <b>5e</b>, has a strong potential to progress to further preclinical studies. Our findings unequivocally showed the effectiveness of 5-FU/pterostilbene hybrids, with the 3,4,5-trimethoxyphenylsubstituted compound serving as a prototype molecule for upcoming studies that focus on new methods for treating colorectal 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 6","pages":"1276 - 1292"},"PeriodicalIF":2.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03401-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125502","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":"Recent progress in synthetic strategies for novel β-lactams linked with five-membered heterocycles (N/O/S): advances in medicinal chemistry (2020–2025)","authors":"Ankita Garg,&nbsp;Dolar Dureja,&nbsp;Raaina Pasricha,&nbsp;Pawan Deep Kaur Saini,&nbsp;Aman Bhalla","doi":"10.1007/s00044-025-03407-3","DOIUrl":"10.1007/s00044-025-03407-3","url":null,"abstract":"<div><p>β-Lactam derivatives have inspired chemists to develop synthetic methods, given the prevalence of β-lactam scaffolds in numerous existing drugs. Recently, the incorporation of β-lactam derivatives into diverse heterocycles using novel pharmacophoric hybridization strategies has led to the development of compounds with significant medicinal applications. The five-membered heterocycles incorporating heteroatoms, such as nitrogen, oxygen, and sulfur, influence their chemical and biological properties. Advances in synthetic strategies, including transition metal catalysis, Staudinger cycloaddition, the Kinugasa reaction, halocyclization, and functionalization using available β-lactam drugs, have facilitated the construction of a variety of β-lactam scaffolds. This article presents an in-depth review of the latest methods for the synthesis of five-membered heterocycles (N/O/S) linked β-lactams from 2020–2025. This review aims to support researchers in designing and developing novel β-lactam linked with five-membered heterocycles (N/O/S) with enhanced therapeutic efficacy by delving into recent advances (2020–2025) in synthetic endeavors for β-lactams.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1145 - 1176"},"PeriodicalIF":2.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125814","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":"CO as a potential therapeutic agent: an initial investigation of dosing and concentration dynamics in solution","authors":"Dongning Liu,&nbsp;Qiyue Mao,&nbsp;Xiaoxiao Yang,&nbsp;Nicola Bauer,&nbsp;Shivanagababu Challa,&nbsp;Binghe Wang","doi":"10.1007/s00044-025-03405-5","DOIUrl":"10.1007/s00044-025-03405-5","url":null,"abstract":"<div><p>Carbon monoxide (CO) is an endogenously produced gaseous signaling molecule that has been shown to have therapeutic values. In studying CO pharmacology, dose dependency has not been properly studied in most, if not all, such work. Part of the reason is the difficulty in determining the solution concentration of a gaseous molecule (CO) with limited water solubility (~1 mM). Along this line, CO solution prepared at a pre-determined concentration has been widely used in studying CO pharmacology. However, different from making a solution of a non-volatile small-molecule drug, CO is expected to quickly escape from the solution, leading to unknown concentrations and an intractable scenario for dose-dependency studies. In this study, we hope to help define the boundary conditions by studying the concentration decay profiles of CO in solution at a pre-determined concentration. Results from such studies will be very important foundational information for future dose-dependency studies of CO pharmacology.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 5","pages":"1136 - 1143"},"PeriodicalIF":2.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918959","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":"Halogens’ effect on human cancer cells of synthesized Vilsmeier reaction-based indole-containing azines derivatives","authors":"Shama Bano,&nbsp;Mohd Asif,&nbsp;Zainab Feroz,&nbsp;Saikh Mohammad Wabaidur,&nbsp;Tazeen Azaz,&nbsp;Snober S. Mir,&nbsp;Abul Hasnat,&nbsp;Abdul Rahman Khan,&nbsp;Malik Nasibullah","doi":"10.1007/s00044-025-03406-4","DOIUrl":"10.1007/s00044-025-03406-4","url":null,"abstract":"<div><p>Herein, Vilsmeier reaction-based synthesized 1H-indole-3-carbaldehyde was utilized in the azines derivatives (<b>6a-d)</b> synthesis through C-5 halogen-substituted oxindoles and their anticancer effect against human cancer cells, as reported. The effect of halogens at C-5 of synthesized compounds (<b>6a-d</b>) on human cancer cells was demonstrated by the National Cancer Institute-Developmental Therapeutics Program, USA. The effect of halogens was notably cytotoxicity against cells, but the bromo-substituted compound <b>6c</b> was further analyzed under five-dose screening at different concentrations, including 10⁻⁴, 10⁻⁶, 10⁻⁵, 10⁻⁷, and 10⁻⁸M. It was concluded that EKVX and UACC-257 cell lines were shown to be −6.58 (lowest) and −4.65 (highest) GI₅₀ at log₁₀ high concentration −4.0, respectively. However, TGI values for RXF and UACC-257 cell lines were shown to be −5.12 (lowest) and −4.0 (more than) at the same concentrations. The lowest LC₅₀ value was calculated at −4.50 for RXF 393 cell line, while the highest LC₅₀ value was noted at less than −4.0 for the T-47D cell of breast cancer at log₁₀ high concentration −4.0, respectively. The aim of research is to demonstrate the halogen’s effects on human cancer cells whenever it is attached at a suitable position at C-5 of the oxindole ring. In the future it could be used as lead molecule in clinical in-vivo investigations on human lung 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 5","pages":"1122 - 1135"},"PeriodicalIF":2.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918925","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 biological evaluation of benzimidazole/bis-imine derivatives as glyoxalase I inhibitors","authors":"Buthina A. Al-Oudat,&nbsp;Suaad A. Audat,&nbsp;Nizar A. Al-Shar’i,&nbsp;Qosay A. Al-Balas,&nbsp;Hana’a M. Jaradat,&nbsp;Lara Fakhouri,&nbsp;Aref L. Zayed","doi":"10.1007/s00044-025-03404-6","DOIUrl":"10.1007/s00044-025-03404-6","url":null,"abstract":"<div><p>Glyoxalase I (Glo-I), a key enzyme involved in cellular detoxification, overexpression of which is implicated in cancer cell survival and proliferation, is a promising therapeutic target. Al-Balas et al. discovered NSCI153166 (IC₅₀ = 0.97 μM) as a potent Glo-I inhibitor through virtual screening of the NCI database. The compound was previously reported as a bis-imine derivative <b>1</b>; however, structural elucidation for the in-house synthesized compound revealed it to be a 1,2-disubstituted benzimidazole <b>2</b>. Surprisingly, both compounds exhibited comparable inhibitory activities. To explore structure-activity relationships, 31 analogues of both scaffolds were synthesized and evaluated against Glo-I. Key findings demonstrated that in the benzimidazole series, both aromatic rings and hydroxyl groups are essential for activity, as removal of the substituted benzyl ring and variations in the phenyl ring substituents led to a complete loss of activity, highlighting the importance of both aromatic rings and the hydroxyl groups, confirmed by docking studies showing crucial interactions of these groups with the Glo-I active site. In the bis-imine series, while modifications to the linker and phenyl rings were tolerated, the scaffold proved to be more fruitful. Notably, <i>meta</i>- and <i>para</i>-substituted bis-imines <b>22</b> (IC₅₀ = 0.86 μM) and <b>23</b> (IC₅₀ = 0.89 μM) exhibited potent activity, comparable to NSCI153166. However, docking studies of <b>23</b> indicated a lack of zinc chelation, suggesting potential for optimization through zinc-chelating substituents. The phenyl linker proved superior to the aliphatic ethylene linker. While both scaffolds show promise as Glo-I inhibitors, further optimization is necessary to enhance potency by exploring alternative linker groups and structural modifications to improve zinc binding affinity, ultimately leading to the development of novel Glo-I inhibitors for cancer therapy.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 5","pages":"1104 - 1121"},"PeriodicalIF":2.6,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919160","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":"Does the negatively charged phosphate backbone contribute to stabilize the complex between cationic organic molecules and G-quadruplex structures? From guessing to calculating","authors":"Francesco Pietra","doi":"10.1007/s00044-025-03403-7","DOIUrl":"10.1007/s00044-025-03403-7","url":null,"abstract":"<div><p>Modeling cationic small-molecule inhibitors of G-quadruplex structures faces controversial opinions as to whether stabilization of the complex can occur by the interaction of the inhibitor with the negatively charged phosphate backbone. The challenge has been taken here of bringing light on such a awful situation by disentangling the energies of interaction of G-quadruplex residues with the inhibitor in a series of representative G-quadruplex complexes. The problem was addressed to computer simulations in the lack of suitable experimental approaches. It emerged that the phosphate contribution can range from dominating to nil, according to whether, in a dynamic course, the inhibitor cationic center can get close to a phosphate group or remain out of the range of coulombic attraction from all them, thus providing guidelines for tailoring the inhibitor toward the best possible stabilization of the complex.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>With two quindoline molecules (top hot pink, bottom green) as inhibitors per G-quadruplex structure, stabilization of the complex by phosphate interaction with the quindoline cationic center is highlighted by interrupted lines.</p></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 5","pages":"1089 - 1103"},"PeriodicalIF":2.6,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919161","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":"6-Phenoxyl-4-aminoquinoline: synthesis and preliminary antitubercular-structure activity relationship analyses","authors":"Richard M. Beteck,&nbsp;Lesetja J. Legoabe,&nbsp;Phelelisiwe S. Dube,&nbsp;Audrey Jordaan,&nbsp;Digby F. Warner","doi":"10.1007/s00044-025-03402-8","DOIUrl":"10.1007/s00044-025-03402-8","url":null,"abstract":"<div><p>Diphenyl ether and quinoline based compounds have been reported to show antibacterial activity. Against <i>Mycobacterium tuberculosis</i>, drug targets inhibited by diphenyl ether compounds are reportedly different from those perturbed by quinoline based antitubercular hits/drugs. Herein, we conceptualized and synthesized novel molecules incorporating quinoline and diphenyl ether moieties. The antitubercular property of the synthesized compounds were measured in vitro using Tween 80 and Tyloxapol supplemented growth media. Compounds in this study generally showed sub micromolar antitubercular activity in tween 80/albumin supplemented growth medium, and moderate to poor activity in tyloxapol/casitone supplemented growth medium. Compound <b>4e</b>, havin a trimethylenediamine moiety and low melting point of 68 °C, emerged as the hit compound, possessing MIC₉₀ value of 0.2 µM. <b>4e</b> is non-cytotoxic when tested against normal human cell line, exhibiting CC₅₀ value &gt; 20 µM.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 5","pages":"1065 - 1073"},"PeriodicalIF":2.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03402-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919029","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}