M. Ahsan, S. Shastri, R. Yadav, M. Hassan, M. Bakht, S. S. Jadav, S. Yasmin
In continuance of our search for newer antiproliferative agents we report herein the synthesis and antiproliferative studies of two series (5a–j and 10a–c) of heterocyclic compounds. All the new compounds were characterized by IR, NMR, and mass spectral data. The antiproliferative activity of 10 compounds (5a–j) was carried out on HeLa (cervix cancer cell line) and MDA-MB-435 (melanoma) and LC50, TGI, and GI50 were calculated, while the antiproliferative activity of 3 compounds (10a–c) was carried out against nine different panels of nearly 60 cell lines (NCI-60) according to the National Cancer Institute (NCI US) Protocol at 10 μM. 1-(7-Hydroxy-4-methyl-2-oxoquinolin-1(2H)-yl)-3-(4-methoxylphenyl)urea (5j) was found to have antiproliferative activity with GI50 of 35.1 μM against HeLa (cervix cancer cell line) and 60.4 μM against MDA-MB-435 (melanoma), respectively. The compounds 10a, 10b, and 10c showed antiproliferative activity with comparatively higher selectivity towards HOP-92 (Non-Small Cell Lung Cancer) with percent growth inhibitions (GIs) of 34.14, 35.29, and 31.59, respectively.
{"title":"Synthesis and Antiproliferative Activity of Some Quinoline and Oxadiazole Derivatives","authors":"M. Ahsan, S. Shastri, R. Yadav, M. Hassan, M. Bakht, S. S. Jadav, S. Yasmin","doi":"10.1155/2016/9589517","DOIUrl":"https://doi.org/10.1155/2016/9589517","url":null,"abstract":"In continuance of our search for newer antiproliferative agents we report herein the synthesis and antiproliferative studies of two series (5a–j and 10a–c) of heterocyclic compounds. All the new compounds were characterized by IR, NMR, and mass spectral data. The antiproliferative activity of 10 compounds (5a–j) was carried out on HeLa (cervix cancer cell line) and MDA-MB-435 (melanoma) and LC50, TGI, and GI50 were calculated, while the antiproliferative activity of 3 compounds (10a–c) was carried out against nine different panels of nearly 60 cell lines (NCI-60) according to the National Cancer Institute (NCI US) Protocol at 10 μM. 1-(7-Hydroxy-4-methyl-2-oxoquinolin-1(2H)-yl)-3-(4-methoxylphenyl)urea (5j) was found to have antiproliferative activity with GI50 of 35.1 μM against HeLa (cervix cancer cell line) and 60.4 μM against MDA-MB-435 (melanoma), respectively. The compounds 10a, 10b, and 10c showed antiproliferative activity with comparatively higher selectivity towards HOP-92 (Non-Small Cell Lung Cancer) with percent growth inhibitions (GIs) of 34.14, 35.29, and 31.59, respectively.","PeriodicalId":19688,"journal":{"name":"Organic Chemistry International","volume":"37 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2016-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76915258","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}
Simple and efficient synthetic procedures were established for the preparation of new energetic covalent compounds, salts, and protonated ionic liquids based on the readily available antimicrobial agent metronidazole. Some of these materials exhibit the desirable properties of energetic materials and energetic ionic liquids, such as low vapor pressure, low melting point, good chemical and thermal stability, and high energetic content. For each of the relevant compounds prepared, thermal stability was determined by differential scanning calorimetry. Some of these compounds may be considered promising precursors of pharmaceuticals such as antimicrobial, antiparasitic, antifungal, antineoplastic agents, or enzyme inhibitors.
{"title":"Synthesis of New Energetic Materials and Ionic Liquids Derived from Metronidazole","authors":"M. A. Romero","doi":"10.1155/2016/4705809","DOIUrl":"https://doi.org/10.1155/2016/4705809","url":null,"abstract":"Simple and efficient synthetic procedures were established for the preparation of new energetic covalent compounds, salts, and protonated ionic liquids based on the readily available antimicrobial agent metronidazole. Some of these materials exhibit the desirable properties of energetic materials and energetic ionic liquids, such as low vapor pressure, low melting point, good chemical and thermal stability, and high energetic content. For each of the relevant compounds prepared, thermal stability was determined by differential scanning calorimetry. Some of these compounds may be considered promising precursors of pharmaceuticals such as antimicrobial, antiparasitic, antifungal, antineoplastic agents, or enzyme inhibitors.","PeriodicalId":19688,"journal":{"name":"Organic Chemistry International","volume":"78 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2016-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81735202","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}
S. Rasool, Aziz‐ur‐Rehman, M. Abbasi, S. Z. Siddiqui, S. A. Shah, S. Hassan, I. Ahmad
Because of the reported biological activities of coumarin, 1,3,4-oxadiazole, and acetamides, some new compounds incorporating these moieties were synthesized and evaluated for their biological potential against Gram-positive and Gram-negative bacteria. In the present work, 4-chlororesorcinol (1) and ethyl acetoacetate (2) were mixed in a strong acidic medium to synthesize 6-chloro-7-hydroxy-4-methyl-2-oxo-2H-chromene (3) which was subjected to the intermolecular cyclization after consecutive three steps to synthesize 5-(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]-1,3,4-oxadiazol-2-thiol (6). A series of acetamoyl electrophiles, 8a–o, were synthesized from aralkyl/alkyl/aryl amines, 7a–o, in an aqueous basic medium. The final compounds, 9a–o, were synthesized by the reaction of compounds 6 and 8a–o in DMF/NaH. The synthesized compounds were structurally elucidated by spectral data analysis of IR, 1H-NMR, and EIMS. The most of the synthesized compounds remained moderate to excellent antibacterial agents. The molecules, 9e, 9j, and 9k, were the most efficient ones against all the five bacterial strains taken into account.
{"title":"Synthesis, Structural Elucidation, and Antibacterial Evaluation of Some New Molecules Derived from Coumarin, 1,3,4-Oxadiazole, and Acetamide","authors":"S. Rasool, Aziz‐ur‐Rehman, M. Abbasi, S. Z. Siddiqui, S. A. Shah, S. Hassan, I. Ahmad","doi":"10.1155/2016/8696817","DOIUrl":"https://doi.org/10.1155/2016/8696817","url":null,"abstract":"Because of the reported biological activities of coumarin, 1,3,4-oxadiazole, and acetamides, some new compounds incorporating these moieties were synthesized and evaluated for their biological potential against Gram-positive and Gram-negative bacteria. In the present work, 4-chlororesorcinol (1) and ethyl acetoacetate (2) were mixed in a strong acidic medium to synthesize 6-chloro-7-hydroxy-4-methyl-2-oxo-2H-chromene (3) which was subjected to the intermolecular cyclization after consecutive three steps to synthesize 5-(6-chloro-4-methyl-2-oxo-2H-chromen-7-yl)oxy]-1,3,4-oxadiazol-2-thiol (6). A series of acetamoyl electrophiles, 8a–o, were synthesized from aralkyl/alkyl/aryl amines, 7a–o, in an aqueous basic medium. The final compounds, 9a–o, were synthesized by the reaction of compounds 6 and 8a–o in DMF/NaH. The synthesized compounds were structurally elucidated by spectral data analysis of IR, 1H-NMR, and EIMS. The most of the synthesized compounds remained moderate to excellent antibacterial agents. The molecules, 9e, 9j, and 9k, were the most efficient ones against all the five bacterial strains taken into account.","PeriodicalId":19688,"journal":{"name":"Organic Chemistry International","volume":"7 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91062112","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}
Vida Saleh, A. Khazaei, Hamid Abizadeh, Shahnaz Saednia
The condensation of O-phenylenediamine (OPD) with aryl aldehydes is carried out in acetonitrile using poly(N,N′-dibromo-N-ethylnaphthyl-2,7-disulfonamide) (PBNS) as a novel and heterogeneous catalyst. PBNS has some potential advantages which include ease of separation from the reaction mixture by simple filtration, easy preparation, recoverablility, convenience, and stability under normal condition and also is not dangerous as molecular bromine.
{"title":"Synthesis, Characterization, and Application of Poly(N,N′-dibromo-N-ethylnaphthyl-2,7-disulfonamide) as an Efficient Reagent for the Synthesis of 2-Arylbenzimidazole and 2-Aryl-1-arylmethyl-1H-1,3-benzimidazole Derivatives","authors":"Vida Saleh, A. Khazaei, Hamid Abizadeh, Shahnaz Saednia","doi":"10.1155/2015/635630","DOIUrl":"https://doi.org/10.1155/2015/635630","url":null,"abstract":"The condensation of O-phenylenediamine (OPD) with aryl aldehydes is carried out in acetonitrile using poly(N,N′-dibromo-N-ethylnaphthyl-2,7-disulfonamide) (PBNS) as a novel and heterogeneous catalyst. PBNS has some potential advantages which include ease of separation from the reaction mixture by simple filtration, easy preparation, recoverablility, convenience, and stability under normal condition and also is not dangerous as molecular bromine.","PeriodicalId":19688,"journal":{"name":"Organic Chemistry International","volume":"44 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2015-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73968943","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}
Urbain C. Kasséhin, F. Gbaguidi, C. N. Kapanda, C. McCurdy, J. Poupaert
This paper reports efforts aimed at tuning up the synthesis of a compound library centered on the general template 2-amino-1-phenyl-2-thioxoethanone taking the condensation of ω-haloacetophenone, octasulfur, and morpholine as pilot reaction. Considerations about atomic economy were found extremely precious in selecting the best starting halo-reagent. A one-pot practical method based on use of 2-bromo-1-phenylethanone as substrate and N,N-dimethylformamide as solvent can be easily scaled up to gram amounts (72% yield). Based on this synthetic approach, some more specific examples are reported.
{"title":"Insight into the Willgerodt-Kindler Reaction of ω-Haloacetophenone Derivatives: Mechanistic Implication","authors":"Urbain C. Kasséhin, F. Gbaguidi, C. N. Kapanda, C. McCurdy, J. Poupaert","doi":"10.1155/2014/486540","DOIUrl":"https://doi.org/10.1155/2014/486540","url":null,"abstract":"This paper reports efforts aimed at tuning up the synthesis of a compound library centered on the general template 2-amino-1-phenyl-2-thioxoethanone taking the condensation of ω-haloacetophenone, octasulfur, and morpholine as pilot reaction. Considerations about atomic economy were found extremely precious in selecting the best starting halo-reagent. A one-pot practical method based on use of 2-bromo-1-phenylethanone as substrate and N,N-dimethylformamide as solvent can be easily scaled up to gram amounts (72% yield). Based on this synthetic approach, some more specific examples are reported.","PeriodicalId":19688,"journal":{"name":"Organic Chemistry International","volume":"6 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2014-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87350667","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}
A series of substituted 1,3,4-oxadiazole derivatives (3a–f) and (6a–f) have been synthesized from diphenylacetic acid hydrazide under microwave irradiation in various reaction conditions. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, and 1H NMR. These targeted compounds have been tested for their antibacterial and antifungal activities compared to ampicillin and griseofulvin as standard drug. Compounds 3a, 3e, 3f, 6c, 6d, 6e, and 6d exhibited the maximum antibacterial activities while 3b, 3c, 3d, 3e, 6a, 6d, and 6e exhibited the maximum antifungal activities.
{"title":"Microwave-Assisted Synthesis of Some 1,3,4-Oxadiazole Derivatives and Evaluation of Their Antibacterial and Antifungal Activity","authors":"Deepak Swarnkar, R. Ameta, Ritu Vyas","doi":"10.1155/2014/694060","DOIUrl":"https://doi.org/10.1155/2014/694060","url":null,"abstract":"A series of substituted 1,3,4-oxadiazole derivatives (3a–f) and (6a–f) have been synthesized from diphenylacetic acid hydrazide under microwave irradiation in various reaction conditions. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, and 1H NMR. These targeted compounds have been tested for their antibacterial and antifungal activities compared to ampicillin and griseofulvin as standard drug. Compounds 3a, 3e, 3f, 6c, 6d, 6e, and 6d exhibited the maximum antibacterial activities while 3b, 3c, 3d, 3e, 6a, 6d, and 6e exhibited the maximum antifungal activities.","PeriodicalId":19688,"journal":{"name":"Organic Chemistry International","volume":"73 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2014-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76439147","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}
The synthesis and biological activity of N-heteroaryl substituted benzene sulphonamides (3a–h) were successful. Simple condensation reaction of benzene sulphonyl chloride (1) with substituted heteroaromatic compounds (2a–h) under dry pyridine and acetone gave the target molecules (3a–h) in good to excellent yield. The compounds were characterized using FTIR, 1HNMR, and 13CNMR. The compounds were screened for antibacterial activity against E. coli, Salmonella typhi, P. aeruginosa, B. cereus, K. pneumonia, and Sarcina lutea and antifungal activity against C. albicans and A. niger. The results of the antimicrobial activity showed improved biological activity against some tested organisms.
{"title":"Synthesis, Characterization, and Evaluation for Antibacterial and Antifungal Activities of N-Heteroaryl Substituted Benzene Sulphonamides","authors":"Christiana Nonye Igwe, U. Okoro","doi":"10.1155/2014/419518","DOIUrl":"https://doi.org/10.1155/2014/419518","url":null,"abstract":"The synthesis and biological activity of N-heteroaryl substituted benzene sulphonamides (3a–h) were successful. Simple condensation reaction of benzene sulphonyl chloride (1) with substituted heteroaromatic compounds (2a–h) under dry pyridine and acetone gave the target molecules (3a–h) in good to excellent yield. The compounds were characterized using FTIR, 1HNMR, and 13CNMR. The compounds were screened for antibacterial activity against E. coli, Salmonella typhi, P. aeruginosa, B. cereus, K. pneumonia, and Sarcina lutea and antifungal activity against C. albicans and A. niger. The results of the antimicrobial activity showed improved biological activity against some tested organisms.","PeriodicalId":19688,"journal":{"name":"Organic Chemistry International","volume":"1 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2014-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76659066","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}
K. Nobuoka, S. Kitaoka, T. Kojima, Y. Kawano, Kazuya Hirano, M. Tange, S. Obata, Yuki Yamamoto, Thomas Harran, Y. Ishikawa
Chiral ionic liquids, starting from (S)-proline, have been prepared and evaluated the ability of a chiral catalyst. In Michael reaction of trans-β-nitrostyrene and cyclohexanone, all the reactions were carried out under homogeneous conditions without any solvent except for excess cyclohexanone. The chiral ionic liquid catalyst with the positive charge delocalized bulky pyrrolidinium cation shows excellent yields (up to 92%), diastereoselectivities (syn/anti = 96/4), and enantioselectivities (up to 95% ee) and could be reused at least three times without any loss of its catalytic activity. Such results demonstrated a promising new approach for green and economic chiral synthesis by using the chiral ionic liquids as a chiral catalyst and a chiral medium.
{"title":"Proline Based Chiral Ionic Liquids for Enantioselective Michael Reaction","authors":"K. Nobuoka, S. Kitaoka, T. Kojima, Y. Kawano, Kazuya Hirano, M. Tange, S. Obata, Yuki Yamamoto, Thomas Harran, Y. Ishikawa","doi":"10.1155/2014/836126","DOIUrl":"https://doi.org/10.1155/2014/836126","url":null,"abstract":"Chiral ionic liquids, starting from (S)-proline, have been prepared and evaluated the ability of a chiral catalyst. In Michael reaction of trans-β-nitrostyrene and cyclohexanone, all the reactions were carried out under homogeneous conditions without any solvent except for excess cyclohexanone. The chiral ionic liquid catalyst with the positive charge delocalized bulky pyrrolidinium cation shows excellent yields (up to 92%), diastereoselectivities (syn/anti = 96/4), and enantioselectivities (up to 95% ee) and could be reused at least three times without any loss of its catalytic activity. Such results demonstrated a promising new approach for green and economic chiral synthesis by using the chiral ionic liquids as a chiral catalyst and a chiral medium.","PeriodicalId":19688,"journal":{"name":"Organic Chemistry International","volume":"10 4 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2014-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90220893","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}
M. Mamaghani, K. Tabatabaeian, R. Araghi, A. Fallah, R. H. Nia
In this report, synthesis of indenopyrido[2,3-d]pyrimidine and pyrimido[4,5-b]quinoline derivatives was investigated via one-pot three-component reaction between 6-amino-2-(alkylthio)-pyrimidin-4(3H)one, 1,3-indanedione, or 1,3-cyclohexadione and arylaldehyde under ultrasonic irradiation in ethylene glycol as solvent at 65°C. In these reactions fused pyrimidine derivatives were synthesized with high to excellent yields (82–97%) and short reaction times (10–33 min).
{"title":"An Efficient, Clean, and Catalyst-Free Synthesis of Fused Pyrimidines Using Sonochemistry","authors":"M. Mamaghani, K. Tabatabaeian, R. Araghi, A. Fallah, R. H. Nia","doi":"10.1155/2014/406869","DOIUrl":"https://doi.org/10.1155/2014/406869","url":null,"abstract":"In this report, synthesis of indenopyrido[2,3-d]pyrimidine and pyrimido[4,5-b]quinoline derivatives was investigated via one-pot three-component reaction between 6-amino-2-(alkylthio)-pyrimidin-4(3H)one, 1,3-indanedione, or 1,3-cyclohexadione and arylaldehyde under ultrasonic irradiation in ethylene glycol as solvent at 65°C. In these reactions fused pyrimidine derivatives were synthesized with high to excellent yields (82–97%) and short reaction times (10–33 min).","PeriodicalId":19688,"journal":{"name":"Organic Chemistry International","volume":"4 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2014-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90844534","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}
Reaction of 2-cyanothiomethylbenzimidazole 1 with an aromatic aldehydes in water under ultrasonic irradiation for 10–13 min gave the corresponding unsaturated nitriles 2a–h which is an efficient and simple method under green conditions. The unsaturated nitrile derivatives were obtained in 86–98% yield with a short reaction time without any tedious workup procedures.
{"title":"An Ultrasound Mediated Green Synthesis of Benzimidazolylthiounsaturatednitriles Using Water as a Green Solvent","authors":"S. Rao, C. V. Reddy, P. Dubey","doi":"10.1155/2014/403803","DOIUrl":"https://doi.org/10.1155/2014/403803","url":null,"abstract":"Reaction of 2-cyanothiomethylbenzimidazole 1 with an aromatic aldehydes in water under ultrasonic irradiation for 10–13 min gave the corresponding unsaturated nitriles 2a–h which is an efficient and simple method under green conditions. The unsaturated nitrile derivatives were obtained in 86–98% yield with a short reaction time without any tedious workup procedures.","PeriodicalId":19688,"journal":{"name":"Organic Chemistry International","volume":"43 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2014-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75946995","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}