Current Bioactive Compounds最新文献

{"title":"Investigation on the Potential of Some N-phenylalkanehydrazides as Superoxide Anion Radical Scavengers and Glutathione Peroxidase Binders\u0000with ADME Prediction: Comparison with Vitamin C","authors":"H. Mouada, T. Lanez","doi":"10.2174/0115734072325272240712114444","DOIUrl":"https://doi.org/10.2174/0115734072325272240712114444","url":null,"abstract":"\u0000\u0000An investigation on the antioxidant activity and ADME properties of some\u0000N-phenylalkanehydrazides (NPhs) in comparison with ascorbic acid was carried out.\u0000\u0000\u0000\u0000The power of the compounds to scavenge the superoxide anion radical\u0000was examined using cyclic voltammetry. Furthermore, molecular docking was used to examine\u0000how NPhs bind to the antioxidant enzyme glutathione peroxidase (GPx). Finally, ADME properties\u0000were predicted using the SwissADME webserver.\u0000\u0000\u0000\u0000The results showed that the studied compounds had significantly higher EC50 values than\u0000Vitamin C and displayed spontaneous binding with GPx with binding energy similar to ascorbic\u0000acid. Also, substantial values emerged from the predictive analysis of drug-likeness and bioavailability\u0000characteristics.\u0000\u0000\u0000\u0000First, the EC50 of the compounds under study was determined by assessing the decrease\u0000in the anodic current peak intensity; this demonstrated significant radical scavenging activity.\u0000Next, the electrostatic way of binding with ROS radical and with antioxidant enzyme was\u0000disclosed by the binding free energies; however, the oxygen and nitrogen atoms in the compounds'\u0000structures might make many conventional hydrogen bonds with amino acids. Finally,\u0000NPh (a) followed all the rules for drug-likeness and bioavailability estimates, making it a promising\u0000moiety for synthesising new antioxidant chemicals.\u0000\u0000\u0000\u0000The current study is a hybrid of experimental and computational methods that complement\u0000each other perfectly.\u0000","PeriodicalId":10772,"journal":{"name":"Current Bioactive Compounds","volume":"23 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141816045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemistry or Hypoglycaemic Aspect of Thiazolidin-2,4-Dione Insight into\u0000the Structure-activity Relationship","authors":"Parvinder Kaur, Nitin Kumar, Shikha Sharma, B. Banik","doi":"10.2174/0115734072316442240603061608","DOIUrl":"https://doi.org/10.2174/0115734072316442240603061608","url":null,"abstract":"\u0000\u0000Heterocyclic compounds that incorporate nitrogen and sulfur, particularly those within\u0000the thiazole family, have garnered significant attention due to their versatile synthetic properties.\u0000This interest arises from their abundance of biologically active natural products and their effectiveness\u0000as potent agrochemicals and pharmaceuticals. Among these, the thiazolidin-2,4-dione\u0000(TZD) motif plays a pivotal role in the biological functions of many important molecules. The\u0000adaptability of the TZD scaffold is further heightened by the potential for substitutions at the third\u0000and fifth positions, rendering it a widely employed moiety with diverse biological effects. TZD\u0000analogs, bearing substitutions at these positions, exhibit a wide spectrum of biological activities,\u0000with a notable emphasis on hypoglycemic effects attributed to enhanced insulin resistance\u0000through the activation of the PPAR-γ receptor. This manuscript aims to present a comprehensive\u0000review of research conducted on TZD derivatives as potential antihyperglycemic agents spanning\u0000from 2010 to the current date. The review encompasses insights into their molecular mechanisms.\u0000Thiazolidin-based chemicals have received significant attention as hypoglycemic agents and provided\u0000information on patents granted for TZD analogs.\u0000","PeriodicalId":10772,"journal":{"name":"Current Bioactive Compounds","volume":"47 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141353281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Potential of Piper cubeba L. f.: A Comprehensive\u0000Review Covering its Phytochemistry, Pharmacology, and Cutting-edge\u0000Applications","authors":"Sonia Singh, Khushi Sharma","doi":"10.2174/0115734072310948240529112415","DOIUrl":"https://doi.org/10.2174/0115734072310948240529112415","url":null,"abstract":"\u0000\u0000Cubeb, often referred to as Piper cubeba (Piperaceae), has a long history in traditional\u0000herbal medicine, particularly in the management of digestive and respiratory disorders. The plant\u0000is a valuable source of essential oils, which are very important economically and are mostly found\u0000in its fruits. Recent research has validated many of the traditional applications and their bioactive\u0000components, highlighting their antibacterial, antioxidant, anticancer, and anti-inflammatory properties.\u0000This article presents a contemporary summary of bioactive compounds and the pharmacological\u0000properties of plants. It also explores the potential of plant P. cubeba for future applications\u0000in promoting health and nutrition.\u0000","PeriodicalId":10772,"journal":{"name":"Current Bioactive Compounds","volume":"95 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141359146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Parameters of Mechanochemical Processing on the Efficacy of Complex Solid Dispersion of Anthelmintics","authors":"A. Varlamova, S. Khalikov, I. Arkhipov, M. Arisov, K. Sadov, Michael M. Ilyin","doi":"10.2174/0115734072303357240528095424","DOIUrl":"https://doi.org/10.2174/0115734072303357240528095424","url":null,"abstract":"\u0000\u0000Due to the fact that animal parasitic diseases often occur in the form\u0000of mixed infections, it is necessary to use complex drugs with a combination of active substances\u0000that act against different classes of helminths. Fenbendazole has a wide spectrum of nematocidal\u0000action and is less effective against cestodes. Considering that sheep are often infected with\u0000both gastro-intestinal nematodes and cestodes, a complex drug based on fenbendazole,\u0000niclosamide with polyvinylpyrrolidone polymer, was developed using mechanochemical\u0000technology in order to increase its solubility and bioavailability and reduce the dosages and side\u0000effects.\u0000\u0000\u0000\u0000This study aimed to evaluate the influence of mechanochemical technology on the efficacy\u0000of complex solid dispersions of anthelmintics against cestodoses and nematodoses.\u0000\u0000\u0000\u0000The influence of different types of mills (roller and planetary mills), levels of energy\u0000intensity (20, 40, 60 g), and component ratio (2:20:78; 3:30:67; 4:40:56) during mechanochemical\u0000processing was studied on the anthelmintic efficacy of complex solid dispersions of fenbendazole,\u0000niclosamide, and polyvinylpyrrolidone in laboratory models of trichinellosis and hymenolepiosis\u0000of white mice, and on sheep naturally infected with helminths.\u0000\u0000\u0000\u0000The efficacy of complex solid dispersions obtained in the planetary mill was higher than\u0000the activity of dispersions obtained in a roller mill. It showed 87.5, 96.36, 83.77, and 99.39% efficacy,\u0000respectively, against experimental trichinellosis, hymenolepiosis of white mice, gastrointestinal\u0000nematode infection and monieziosis of sheep at a ratio of 2:20:78. The basic drug –\u0000fenbendazole demonstrated 31.37 and 22.77% activity against experimental trichinellosis and\u0000gastro-intestinal nematode infection of sheep. The basic drug, niclosamide, showed 36.37% efficacy\u0000against hymenolepiosis in mice and 28.31% against monieziosis in sheep. It was established\u0000that with an increase in the energy intensity level of the planetary mill (20, 40, and 60 g), the decrease\u0000in the efficacy of solid dispersion occurred from 73.90 to 59.12% against T. spiralis and\u0000from 92.73% to 79.81% against H. nana.\u0000\u0000\u0000\u0000The use of mechanochemical technology for the production of solid dispersions\u0000of fenbendazole and niclosamide with polyvinylpyrrolidone makes it possible to increase the\u0000anthelmintic efficacy by 2.7–3 times compared to the activity of basic substances. It was\u0000noted that the complex solid dispersions of anthelmintics obtained in a planetary mill had\u00007.51–10.17% greater activity in comparison with the samples obtained in a roller mill. The most\u0000optimal ratio of active substances was 2:20:78 at a 20 g level of energy intensity of the planetary\u0000mill.\u0000","PeriodicalId":10772,"journal":{"name":"Current Bioactive Compounds","volume":" 84","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141374794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, In vitro Antimicrobial and Antioxidant Evaluation of\u0000Novel Pyrimidine Derivatives","authors":"Kaushal Arora, Prabhakar Kumar Verma","doi":"10.2174/0115734072301970240528053901","DOIUrl":"https://doi.org/10.2174/0115734072301970240528053901","url":null,"abstract":"\u0000\u0000In this study, a new series of 2-amino-6-(substituted)pyrimidin-4-yl-2Hchromen-\u00002-one analogues (S1-S15) was prepared by using the Knovengeal condensation method\u0000and evaluated for antimicrobial as well as antioxidant activity.\u0000\u0000\u0000\u0000To ensure the progress and confirmation of the reactions, TLC was employed. The melting\u0000points (MP) were ascertained utilising a Sunbim-made sonar melting point device produced in India.\u0000To confirm the chemical structures of these compounds, we employed a range of techniques, including\u0000FT-IR, MS, 1H-NMR, and Elemental analysis. The antimicrobial and antifungal activity was\u0000evaluated using the tube dilution method, and a DPPH assay was used to assess antioxidant activity.\u0000\u0000\u0000\u0000Within the series, S1 demonstrated strong antibacterial efficacy against S. Aureus, with a minimum inhibitory concentration value of 16.26μg/ml, while compound S7 displayed significant potential against B. subtilis and E. coli, with a MIC value of 17.34μg/ml. For antifungal activity, compounds S7 and S11 are the most potent against A. niger, showing a minimum inhibitory concentration of 17.34μg/ml. In the evaluation of antioxidant activity, it was observed that compounds S2 and S4 displayed outstanding antioxidant properties, with IC50 values of 13.33μg/ml and 43.13μg/ml.\u0000\u0000\u0000\u0000The newly created derivatives exhibited robust antimicrobial and antioxidant characteristics\u0000upon assessment through designated methodologies, surpassing the efficacy of conventional\u0000drugs in the comparative analysis. Notably, compounds S1, S2, S7, S4, and S11 exhibited even\u0000greater activity than the reference drugs. Their structure-activity relationship was also discussed.\u0000","PeriodicalId":10772,"journal":{"name":"Current Bioactive Compounds","volume":"22 46","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141380174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Chemistry and Biological Activity of Sulphonamides","authors":"Mahmoud N. M. Yousif","doi":"10.2174/0115734072310728240528071149","DOIUrl":"https://doi.org/10.2174/0115734072310728240528071149","url":null,"abstract":"<jats:sec>\u0000<jats:title/>\u0000<jats:p/>\u0000</jats:sec>","PeriodicalId":10772,"journal":{"name":"Current Bioactive Compounds","volume":"242 3‐5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141386748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-carcinogenic Potential of Nano-curcumin -“Killing Cancerous Cells”","authors":"Mohsin Ali Khan, Anwar Khan, Akhlak Ahmed Khan, Simrah, Mohd. Aamir Mirza, Kamran Javed Naquvi, Devendra Kumar","doi":"10.2174/0115734072294675240502065442","DOIUrl":"https://doi.org/10.2174/0115734072294675240502065442","url":null,"abstract":"\u0000\u0000Nowadays, cancer treatment is currently limited to surgery, chemotherapy, and radiation,\u0000which carry the risk of damaging the normal tissue of the body and incomplete removal of\u0000the cancerous cells from the body. Thus, the Nano technique offers a great means to target therapies\u0000directly on cancerous cells and neoplasm. Moreover, because nano-based formulations of\u0000polyphenolic curcumin show a major effect on cancer and tumour cells, nanoparticles have a tendency\u0000to overcome the hydrophobic nature of curcumin to improve its stability and bioavailability\u0000in vitro and in vivo. It is apparent from the studies that Curcumin has shown anticancer effects by\u0000regulating various immunomodulators, which include cytokines, reactive oxygen species, and\u0000cyclooxygenase-2 (COX-2). It also takes part in the downregulation of growth factors, protein\u0000kinases, oncogenic molecules, and various signalling pathways, such as nuclear factor kappalight-\u0000chain enhancer of activated B cells (NF-κB), c-Jun N-terminal kinase (JNK), and signal\u0000transducer and activator of transcription 3 (STAT3) signalling. According to recent studies and\u0000clinical trials, nano curcumin shows a major effect on cancerous cells. In this article, the authors\u0000summarised the mechanism of nano curcumin in various metastatic cancers and the most recent\u0000clinical trials performed.\u0000","PeriodicalId":10772,"journal":{"name":"Current Bioactive Compounds","volume":"138 41","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140976376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron(III) Monoglycerolate: A Potential Hemostatic Agent for Topical Application","authors":"Tat’yana Khonina, Alexander Safronov, M. Bulatova, L. Larionov, Irina Antropova, M. Dobrinskaya, N. Izmozherova, D. Tishin, Semyon Alekseenko, E. Bogdanova, Maxim Karabanalov, O. Chupakhin","doi":"10.2174/0115734072295011240425080837","DOIUrl":"https://doi.org/10.2174/0115734072295011240425080837","url":null,"abstract":"\u0000\u0000Glycerolates of biogenic elements are of interest because of their pharmacological\u0000activity. Some of them are used as active substances in agents for topical application\u0000and as biocompatible precursors in sol-gel synthesis of bioactive materials.\u0000\u0000\u0000\u0000In this work, morphostructural feature, ability to hydrolyze, and the pharmacological\u0000activity of previously synthesized iron(III) monoglycerate were studied.\u0000\u0000\u0000\u0000Analytical techniques, including SEM, TEM, XRD, TGA, IR spectroscopy, DLS and\u0000ELS, were used. Hemostatic activity was studied in vivo, and primary toxicological studies were\u0000carried out on experimental animals. Antimicrobial activity was studied using the agar diffusion\u0000method.\u0000\u0000\u0000\u0000When dispersed in glycerol, solid crystalline iron(III) monoglycerolate transforms into\u0000an amorphous state, forming aggregates with an average particle size of 250 nm (according to\u0000DLS data). It slowly hydrolyzes in water at room temperature, while hydrolysis does not take\u0000place in an aqueous glycerol media. Iron(III) monoglycerolate is nontoxic and exhibits pronounced\u0000hemostatic activity and low antibacterial activity (relative to the strain S. аureus).\u0000\u0000\u0000\u0000Iron(III) monoglycerolate can be considered a potential hemostatic agent, showing\u0000promise for topical application in medical and veterinary practice, as well as a novel biocompatible\u0000precursor in the sol-gel synthesis of practically useful substances.\u0000","PeriodicalId":10772,"journal":{"name":"Current Bioactive Compounds","volume":" 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140996530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Activity and GC-MS Profiling of Bioactive Constituents in the Methanolic Extracts of Spatoglossum variabile and Gracilaria corticata","authors":"S. Sruthi, Shahjahan A, Kumaran K, Dannie Macrin, Vijay Murali RM, K.N. Aruljothi","doi":"10.2174/0115734072296835240409124751","DOIUrl":"https://doi.org/10.2174/0115734072296835240409124751","url":null,"abstract":"\u0000\u0000Marine algae stand out as repositories of bioactive metabolites, widely\u0000harnessed in treating diverse diseases. Given the often-challenging side effects associated with\u0000conventional cancer treatments, researchers are increasingly turning their attention to marine algae\u0000as a promising source for discovering novel and potent anticancer compounds. In this study,\u0000we meticulously explored the potential anticancer activity of Spatoglossum variabile and\u0000Gracilaria corticata sourced from the Indian Ocean.\u0000\u0000\u0000\u0000Marine algae are rich in bioactive metabolites that are extensively used to treat various diseases. Researchers have considered marine algae for novel and promising anticancer compounds due to the adverse effects of standard cancer treatments\u0000\u0000\u0000\u0000The secondary metabolites were extracted using methanol solvent according\u0000to the standard protocol. The extract was subjected to GC-MS analysis and evaluated for\u0000its short- and long-term cytotoxicity and anti-proliferative ability in the HCT116 cell line using\u0000MTT, clonogenic, and trypan blue dye exclusion assays, respectively.\u0000\u0000\u0000\u0000The methanolic extract of Spatoglossum variabile contained 21 unique\u0000anticancer compounds, except for the other bioactive compounds. The results indicate that increasing\u0000the concentration of algal extracts decreased the cell viability significantly, with an IC50\u0000of 51.49 μg/mL and 37.50 μg /mL in the HCT116 cell line. The results showed a significant reduction\u0000in colorectal cancer colony formation and a gradual reduction in cell proliferation. These\u0000results underscore the potential for targeted, low-toxicity biomedicines due to their selective cytotoxicity\u0000against cancer cells.\u0000\u0000\u0000\u0000The extract was subjected to GC-MS analysis and evaluated for its short- and long-term cytotoxicity and anti-proliferative ability in HCT116 cell line using MTT, clonogenic, and trypan blue dye exclusion assays, respectively.\u0000\u0000\u0000\u0000Our findings show that Spatoglosuum variabile & Gracilaria corticata extracts contain\u0000various bioactive compounds, display long-term and short-term cytotoxicity and antiproliferative\u0000effects, which indicates that their constituent compounds might be further refined\u0000into effective anti-colorectal cancer medications.\u0000\u0000\u0000\u0000The methanolic extract of Spatoglossum variabile contained 21 unique anti-cancer compounds, in addition to other bioactive compounds. The results indicate that increasing the concentration of algal extracts decreased the cell viability significantly, with an IC50 of 51.49 µg/mL and 37.50 µg /ml in the HCT116 cell line. The results showed a significant reduction in colony formation and a gradual reduction in cell proliferation\u0000","PeriodicalId":10772,"journal":{"name":"Current Bioactive Compounds","volume":"63 40","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140664067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xanthone Derivatives: A Pharmacological Panorama of Versatility","authors":"Anuradha Mehra, Rekha Sangwan, Emmanuel Owusu","doi":"10.2174/0115734072278162240406123303","DOIUrl":"https://doi.org/10.2174/0115734072278162240406123303","url":null,"abstract":"\u0000\u0000Xanthones are a class of naturally occurring compounds found in various plant\u0000sources. Over the years, studies have revealed therapeutic impending xanthones in treating and\u0000managing several ailments, including cancer, inflammation, and microbial infections. Xanthones\u0000exert their therapeutic effects through various mechanisms, such as anti-inflammatory, antioxidant,\u0000and anti-proliferative activities. It has also been found that xanthones induce apoptosis, inhibit\u0000cell proliferation, and arrest cell cycles by modulating several signaling pathways. This review\u0000objective is to deliver an inclusive overview of the therapeutic essence of xanthones and\u0000their potential use as a natural remedy for managing and treating various diseases.\u0000","PeriodicalId":10772,"journal":{"name":"Current Bioactive Compounds","volume":" 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140689828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}