Archiv der Pharmazie最新文献

{"title":"Novel Purine-Based Natural Products as Inhibitors of Cholinesterases and Monoamine Oxidases Presenting Potential Multitarget Therapeutics Tackling Alzheimer's Disease","authors":"Amira E. Shaaban,&nbsp;Ahmed R. Ali,&nbsp;Seif N. Ayyad,&nbsp;Farid A. Badria","doi":"10.1002/ardp.70035","DOIUrl":"https://doi.org/10.1002/ardp.70035","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) is a complex neurological disorder that arises from multiple factors. The innovative multitarget-directed ligand (MTDL) approach, which incorporates multiple pharmacophores into one molecule, enhances the development of effective therapeutics for AD. Eighteen novel natural product-based purine MTDLs were synthesized. These hybrids were evaluated In Vitro for their inhibitory effects on AChE, BChE, MAO-A, and MAO-B. The findings revealed that most hybrids effectively and selectively inhibited AChE. Hybrid <b>9b</b> demonstrated the highest inhibitory potency against AChE, BChE, MAO-A, and MAO-B, exhibiting IC₅₀ values of 5.52, 11.64, 25.99, and 34.78 µM, respectively. In addition, hybrid <b>9b</b> exhibited interesting antioxidant activity, with an IC₅₀ of 6.69 µM. The mechanism of action and the binding modes of hybrid <b>9b</b> were analyzed through molecular docking studies. Molecular dynamics simulation revealed that hybrid <b>9b</b> is stable within the AChE active site. In Silico assessments of physicochemical properties for hybrid <b>9b</b> indicate that it is well absorbed following oral administration and can penetrate brain tissue. Finally, hybrid <b>9b</b> stability studies in simulated gastric and intestinal conditions suggested that it could be absorbed into the bloodstream without significant degradation. Consequently, these findings reinforce the potential therapeutic applications of hybrid <b>9b</b> as a multifunctional therapeutic candidate for addressing AD.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DCAF16-Based Covalent Molecular Glues for Targeted Protein Degradation of Histone Deacetylases","authors":"Tao Sun,&nbsp;Shiyang Zhai,&nbsp;Stephan Lepper,&nbsp;Beate König,&nbsp;Mateo Malenica,&nbsp;Irina Honin,&nbsp;Finn K. Hansen","doi":"10.1002/ardp.70045","DOIUrl":"https://doi.org/10.1002/ardp.70045","url":null,"abstract":"<p>Histone deacetylases (HDACs) are intriguing cancer targets due to their high expression in many tumors. Consequently, inhibition or degradation of HDACs can be beneficial for cancer therapy. Targeted protein degradation using molecular glues represents a promising therapeutic approach, enabling the specific degradation of numerous disease-causing proteins. However, the rational design of molecular glues in a target-based manner remains challenging. A recent study has described the identification of a DCAF16-based covalent linker-less chemical handle for molecular glues. This covalent warhead can be attached to protein of interest ligands to induce the targeted degradation of various protein classes. Inspired by this, we designed and synthesized a new class of DCAF16-based covalent molecular glues utilizing different zinc-binding groups for the targeted degradation of HDACs. This approach led to the discovery of an efficient molecular glue (<b>10a</b>) that reduced HDAC1 levels in multiple myeloma MM.1S cells in a potent and preferential manner.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining Cyclic Triimidazo Triazine Core With Ethynyl-N-Methyl-Pyridinium Groups for Targeting G-Quadruplex Structures","authors":"Chiara Platella,&nbsp;Stefano Di Ciolo,&nbsp;Andrea Criscuolo,&nbsp;Daniele Malpicci,&nbsp;Rosa Gaglione,&nbsp;Angela Arciello,&nbsp;Domenica Musumeci,&nbsp;Elena Lucenti,&nbsp;Elena Cariati,&nbsp;Daniela Montesarchio,&nbsp;Clelia Giannini","doi":"10.1002/ardp.70037","DOIUrl":"https://doi.org/10.1002/ardp.70037","url":null,"abstract":"<p>The synthesis and characterization of a mini-library of cyclic triimidazo triazine (<b>TT</b>) derivatives functionalized with one, two, or three ethynyl-<i>N</i>-methyl-pyridinium moieties are reported here. These compounds were designed with the aim of targeting cancer-related DNA G-quadruplex structures. The newly synthesized compounds were tested for their ability to bind G-quadruplexes from both telomeric and oncogene promoter sequences using an affinity chromatography-based assay, spectroscopic and electrophoretic techniques, as well as molecular docking analysis. The obtained results demonstrated the effective capacity of the investigated compounds to specifically recognize the selected G-quadruplex models, with their <b>TT</b> cores targeting the outer G-quartets and their positively charged <i>N</i>-methyl-pyridinium groups interacting with the top edge of G-quadruplex grooves. Notably, the trisubstituted cyclic triimidazole compounds showed higher stabilizing properties than the related disubstituted derivatives, which in turn were stronger binders than their monosubstituted analogs. However, the mono- and disubstituted derivatives showed higher G-quadruplex versus duplex recognition selectivity compared with the trisubstituted ones. Altogether, the biophysical experiments, also in agreement with the biological assays, underlined the advantage of introducing an alkyne linker between the triimidazole core and the methylpyridinium group, proving to be beneficial to increase both the stabilizing effects on the G-quadruplexes and the anticancer activity compared with the analogs of the same family lacking the alkyne linker.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quinolinone Derivatives Suppress Angiogenesis in Human Umbilical Vein Endothelial Cells by Blocking the VEGF-Induced VEGFR2 Signaling Pathway","authors":"Xiaoxi Lin,&nbsp;Bonian Chen,&nbsp;Xiao Xiao,&nbsp;Rui Wang,&nbsp;Weiming Yao,&nbsp;Ao Li","doi":"10.1002/ardp.70040","DOIUrl":"https://doi.org/10.1002/ardp.70040","url":null,"abstract":"<div>\u0000 \u0000 <p>Targeting the vascular endothelial growth factor (VEGF) pathway is crucial for antiangiogenesis therapy in treating cancers and diseases with abnormal blood vessel growth. Human umbilical vein endothelial cells (HUVECs) activated by VEGF are widely used for exploring the impact of antiangiogenic agents on cellular functions. In this study, seven quinolinone derivatives were successfully synthesized and structurally confirmed through ¹H, ¹³C NMR, and HRMS spectra. Compounds <b>4</b> and <b>5</b> exhibited significant inhibition of VEGF-induced HUVEC proliferation, with IC₅₀ values of 84.8 and 58.1 μM for 48 h. Compounds <b>3</b>‒<b>6</b> effectively suppressed VEGF-induced HUVEC migration and invasion, demonstrating potent inhibitory effects in the Matrigel tube formation assay. Compounds <b>4</b> and <b>5</b> directly bind to vascular endothelial growth factor receptor 2 (VEGFR2), thereby inhibiting VEGFR2-mediated downstream angiogenic signaling pathways (PI3K/Akt, ERK1/2/p38 MAPK, and FAK). Cell-cycle analysis revealed that compounds <b>4</b> and <b>5</b> induced substantial G₂/M phase arrest in HUVECs, accompanied by increased p53 phosphorylation and upregulation of p21^cip1 expression. Compounds <b>3</b>‒<b>6</b> also induced apoptosis in HUVECs, as evidenced by nuclear condensation, DNA laddering, and increased Annexin V/PI staining. Western blot analysis showed that compounds <b>4</b> and <b>5</b> significantly increased the levels of apoptosis-related proteins, particularly cleaved caspase-3 and PARP. Through in vivo experiments utilizing the chicken embryo chorioallantoic membrane (CAM) assay, a marked decline in newly formed microvessels was observed posttreatment with both compounds. These results suggest that compounds <b>4</b> and <b>5</b> show promise as antiangiogenic agents, warranting further investigation into their therapeutic efficacy in conditions characterized by abnormal angiogenesis.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of New Thiadiazole Derivatives as VEGFR-2 Inhibitors With Anticancer and Proapoptotic Activities‏","authors":"Hazem Elkady,&nbsp;Walid E. Elgammal,&nbsp;Mohamed M. Khalifa,&nbsp;Hazem A. Mahdy,&nbsp;Ahmed S. Ibrahim,&nbsp;Abdullah Y. Saad,&nbsp;Bshra A. Alsfouk,&nbsp;Eslam B. Elkaeed,&nbsp;Ahmed M. Metwaly,&nbsp;Ibrahim H. Eissa","doi":"10.1002/ardp.70042","DOIUrl":"https://doi.org/10.1002/ardp.70042","url":null,"abstract":"<div>\u0000 \u0000 <p>A series of thiadiazole-based derivatives were synthesized and evaluated for their potential as VEGFR-2 inhibitors and anticancer agents. Among them, compound <b>7b</b> demonstrated significant cytotoxic activity against MCF-7 breast cancer cells, with an IC₅₀ value of 6.13 µM, surpassing that of the reference drug sorafenib (IC₅₀: 7.26 µM). Compound <b>7b</b> also exhibited potent VEGFR-2 inhibition with an IC₅₀ of 40.65 nM, outperforming sorafenib (IC₅₀: 53.32 nM). Further investigation into the mechanism of action revealed that compound <b>7b</b> induced significant changes in the cell-cycle distribution of MCF-7 cells, causing G1 arrest and delaying progression through the G2/M phase. Apoptosis analysis demonstrated that compound <b>7b</b> primarily induced late apoptosis (55.90%) and necrosis (21.81%), with only 22.26% of cells remaining viable. Treatment with <b>7b</b> increased the expression of the proapoptotic gene BAX (4.19 ± 0.34-fold) and suppressed the expression of the antiapoptotic gene Bcl-2 (0.38 ± 0.02-fold), resulting in a dramatic increase in the BAX/Bcl-2 ratio (11.03 ± 1.66-fold). Additionally, caspase-8 and caspase-9 levels were elevated by 2.99 ± 0.22-fold and 4.13 ± 0.11-fold, respectively, confirming activation of both intrinsic and extrinsic apoptotic pathways. In conclusion, compound <b>7b</b> is a potent VEGFR-2 inhibitor with promising anticancer activity, demonstrating cytotoxicity, inhibition of cell migration, and induction of apoptosis in MCF-7 cells. These results suggest that compound <b>7b</b> has the potential to be developed as a therapeutic agent for breast cancer treatment, warranting further in vivo and mechanistic studies.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New D-π-A-Based Coumarin- Derived Fluorescent Theranostic Probes With Broad-Spectrum Antimicrobial Activity","authors":"Himanshu Rai,&nbsp;Atul Kumar Tiwari,&nbsp;Aishwarya Nikhil,&nbsp;Ankit Tiwari,&nbsp;Prahalad Singh Bharti,&nbsp;Suresh Kumar Maury,&nbsp;Munesh Kumar Gupta,&nbsp;Sundaram Singh,&nbsp;Saroj Kumar,&nbsp;Gyan Modi","doi":"10.1002/ardp.70032","DOIUrl":"https://doi.org/10.1002/ardp.70032","url":null,"abstract":"<div>\u0000 \u0000 <p>Understanding how multidrug-resistant (MDR) bacteria and fungi defy the existing antimicrobial agents requires innovative tools and techniques for real-time, in situ exploration of bacterial responses to antibiotics. Fluorescence-tagged antibiotics or dyes with inherent antimicrobial activity can provide a profound understanding of the molecular biology underlying antibiotic action and resistance mechanisms. Cutting-edge research highlights the pursuit of benzo-α-pyrone (coumarin) derivatives due to their excellent pharmacokinetics, diverse pharmacological activities, and innovative fluorescence molecular probes. In this study, donor-π-acceptor-based coumarin dyes were designed and evaluated for antimicrobial efficacy against fungal strains (<i>Candida albicans</i>), Gram-negative pathogens (<i>Escherichia coli</i>), and Gram-positive bacteria (<i>Staphylococcus aureus</i>). I-6 exhibited notable antimicrobial activity against <i>S. aureus</i> and <i>C. albicans</i> compared with <i>E. coli</i>. Conversely, I-9, a congener of I-6, showed a comparable affinity for <i>S. aureus</i> but found poor activity against the remaining tested strains. Mechanistic investigative studies unveiled that the inhibitory efficacy of I-6 can be attributed to its capacity to generate high reactive oxygen species (ROS) formation. Despite the evident antimicrobial potential of I-6 in the data, our future prospects, including real-time visualization to study physiological processes like uptake, distribution, and mechanism of action through fluorescence-based imaging modalities, could enhance the applicability of these probes.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information: Arch Pharm (7/2025)","authors":"","doi":"10.1002/ardp.70052","DOIUrl":"https://doi.org/10.1002/ardp.70052","url":null,"abstract":"","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in 5-Ene-2,4-thiazolidinediones Research: Multifaceted Biological Profile, Structure–Activity Relationship, and Mechanisms of Action","authors":"Neeru Malik,&nbsp;Rajesh Kumar Singh","doi":"10.1002/ardp.70026","DOIUrl":"https://doi.org/10.1002/ardp.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Recent advances in the chemistry of 5-ene-2,4-thiazolidinediones (5-ene-2,4-TZDs) has revealed their broad therapeutic potential, owing to their structural adaptability and ability to engage multiple biological targets. These compounds exhibit potent anti-inflammatory and antioxidant effects through both PPAR-γ- and Nrf2-independent mechanisms, alongside significant antibacterial and antifungal activity. Strategic N3 substitutions and hybrid pharmacophores have further enhanced their efficacy, particularly in treating inflammatory and infectious comorbidities. Importantly, the electrophilic nature of the 5-ene moiety may confer target promiscuity, enabling covalent interactions with nucleophilic residues in protein active sites. This review summarizes recent advances in the synthesis, pharmacological profiling, and SAR of 5-ene-2,4-TZDs, highlighting key molecular interactions with targets such as NF-κB and ROS modulators. By offering mechanistic insights and design strategies, this study provides a roadmap for developing next-generation 5-ene-2,4-TZDs with optimized activity and safety.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quinazolin-4(3H)-One-Based New Glitazones as Dual Inhibitors of α-Glucosidase and Aldose Reductase: Comprehensive Approaches for Managing Diabetes Mellitus and Its Complications","authors":"Feyzi Sinan Tokalı,&nbsp;Yeliz Demir,&nbsp;Şeyma Ateşoğlu,&nbsp;Pelin Tokalı,&nbsp;Halil Şenol","doi":"10.1002/ardp.70033","DOIUrl":"https://doi.org/10.1002/ardp.70033","url":null,"abstract":"<div>\u0000 \u0000 <p>A series of novel glitazones containing thiazolidine-2,4-dione and quinazolin-4(3<i>H</i>)-one moieties were synthesized to explore their potential as dual inhibitors of aldose reductase (ALR2) and α-glucosidase (α-Glu), two key enzymes involved in diabetes and its complications. In vitro assays revealed that compounds <b>8</b> (cyclohexyl substituted), <b>9</b> (phenethyl substituted), and <b>11</b> (phenyl substituted) exhibited potent inhibitory effects on both enzymes, with <b>11</b> being the most active, showing an ALR2 inhibition (<i>K</i>_i = 0.106 µM) approximately nine times more effective than the standard epalrestat (EPR) (<i>K</i>_i = 0.967 µM) and α-Glu inhibition (<i>K</i>_i = 0.648 µM) about six times stronger than acarbose (ACR) (<i>K</i>_i = 0.3.775 µM). Molecular docking and molecular dynamics simulations showed that compound <b>11</b> formed strong interactions with residues Trp-20, Gln-183, and Asp-43 for ALR2 and residues Arg-200, Arg-400, and Glu-271 for Phe-297. Cytotoxicity assays performed on healthy cell lines (HUVEC and BEAS-B2) revealed that the tested compounds were nontoxic at inhibitory concentrations. These findings highlight the potential of compound <b>11</b> as a promising dual inhibitor for managing diabetes and its complications, providing a foundation for further optimization and therapeutic exploration.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benzamide-Containing Histone Deacetylase Inhibitors With Anticancer Therapeutic Potential","authors":"Juntao Song,&nbsp;Shujing Si,&nbsp;Jie Qin,&nbsp;Zhenguo Liu","doi":"10.1002/ardp.70028","DOIUrl":"https://doi.org/10.1002/ardp.70028","url":null,"abstract":"<div>\u0000 \u0000 <p>Histone deacetylases (HDACs) could regulate gene expression, arrest the cell cycle, alter epigenetics, promote angiogenesis, and evade cancer cell survival and apoptosis. HDAC inhibitors could act on cancer cells through multiple mechanisms, primarily by regulating gene expression, inducing cell-cycle arrest, promoting apoptosis, inhibiting angiogenesis, enhancing the immune response, and modifying the epigenome, representing valuable chemical entities for cancer therapy. The benzamide derivatives can chelate with the zinc ion at the active site of HDACs, interact with the surrounding amino acid residues in the active site cavity of HDACs, and cause conformational changes in HDACs. Accordingly, benzamide derivatives are useful HDAC inhibitors, and the benzamide-containing HDAC inhibitors have the potential to demonstrate robust anticancer activity. The purpose of this review is to summarize the current scenario of benzamide-containing HDAC inhibitors with anticancer therapeutic potential developed since 2020 to facilitate further rational exploitation of more effective candidates.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}