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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Research Article

Synthesis, Antimicrobial Evaluation and Molecular Docking of Some Potential 2,6-disubstituted 1H-Benzimidazoles; Non-Classical Antifolates

Author(s): Sunil Harer*, Manish Bhatia and Vikram Kawade

Volume 15, Issue 7, 2019

Page: [813 - 832] Pages: 20

DOI: 10.2174/1573406415666190206231555

Price: $65

Abstract

Background: Dihydrofolate reductase is one of the important enzymes for thymidylate and purine synthesis in micro-organisms. A large number of drugs have been designed to inhibit microbial DHFR but over the period of time, some drugs have developed resistance and cross reactivity towards the enzyme. Over the past few decades, benzimidazoles, triazoles and their derivatives have been grabbing the attention of the synthetic chemists for their wide gamut of antibacterial and antifungal activities targeting microbial protein DHFR.

Objective: Our goal behind present investigation is to explore benzimidazoles class of drugs as microbial DHFR inhibitors by studying ligand-receptor binding interactions, in vitro enzyme inhibition assay and confirmation of anti-microbial activity against selected pathogenic microorganisms.

Methods: A library containing thirty novel 2,6-disubstituted 1H-benzimidazoles was synthesized by one pot condensation of o-nitro aniline or 2,4-dinitro aniline with series of aldehydes or acetophenones using Na2S2O4 or SnCl2 respectively and reflux for 5-6hr. Structures of compounds have been confirmed by spectroscopic methods as 1H and 13C NMR, FT-IR and MS. In vitro DHFR inhibition study was performed by using Epoch microplate reader and IC50 of the test compounds was compared with Trimethoprim. In vitro antimicrobial activity was performed against selected clinical pathogens by agar disk diffusion method and MIC (µg/mL) was reported.

Results: Moderate to good level of DHFR inhibition was observed with IC50 values in the range of 7-23 µM. Compounds B1, B19, B22, B24 and B30 expressed 1.1 to 1.4 folds more prominent DHFR inhibitory activity as compared to standard Trimethoprim. Remarkable antimicrobial activity was exhibited by B1, B19, B22, B24 and B30. Molecular docking study revealed perfect binding of test ligands with key amino acids of DHFR as Phe31, Ile94, Ile5, Asp27, Gln32 and Phe36.

Conclusion: Nature of 1H-benzimidazole substituents at position 2 and 6 had influence over magnitude and type of molecular binding and variation in the biological activity. The present series of 1H-benzimidazoles could be considered promising broad-spectrum antimicrobial candidates that deserve in future for preclinical antimicrobial evaluation and development of newer antimicrobial agents targeting microbial DHFR.

Keywords: 1H-benzimidazoles, DHFR, molecular modeling, antimicrobial activity, agar disk diffusion, MIC, IC50.

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[1]
Singh, N.; Pandurangan, A.; Rana, K.; Anand, P.; Ahmed, A.; Tiwari, A.K. Benzimidazole: A short review of their antimicrobial activity. Int. Curr. Pharm. J., 2012, 1(5), 119-127.
[2]
Nadeem, S.; Waquar, A.; Shamsher, A.; Ruhi, A.; Jain, S.; Azad, B.; Akhtar, J. Triazoles as potential bioactive agents. Int. J. Pharm. Sci. Rev. Res., 2011, 8(1), 161-169.
[3]
Monika, G.; Shivi, B.J. 1,3,4-Oxadiazole as antimicrobial agents: An overview. Chem. Pharm. Res., 2011, 3(3), 137-147.
[4]
Periti, P. Brodimoprim, a new bacterial dihydrofolate reductase inhibitor: A mini review. J. Chemother., 1995, 7(3), 221-223.
[5]
Somisetti, N.R.; Ravisankar, T.; Latha, J.; Sudhakar, B.K. Synthesis, characterization and antimicrobial activity of novel biphenyl tetrazoles. Der. Pharma Chem., 2012, 4(3), 1093-1103.
[6]
Moni, S.; Prem, M.S.C. Dihydrofolate reductase as therapeutic target for infectious diseases: Opportunities and challenges. Future Med. Chem., 2012, 4(10), 1335-1365.
[7]
Bayomi, S.M.; Maarouf, A.R.; Abdel, A.N.I.; Ahmed, A.B.M. Synthesis, molecular modeling study, preliminary antitumor and antimicrobial evaluation of new benzimidazole derivatives. J. Am. Sci., 2013, 9(10), 42-48.
[8]
Chowdhury, S.F.; Guerrero, R.H.; Reto, B.R. Synthesis and testing of 5-benzyl-2,4-diaminopyrimidines as potential inhibitors of leishmanial and trypanosomal dihydrofolate reductase. J. Enzyme Inhib. Med. Chem., 2002, 17(5), 293-302.
[9]
Hassan, H.S.; El-Messery, S.M.; Al-Omary, F.A.; Al-Rashood, S.T.; Shabayek, M.I.; Abulfadl, Y.S. Habib, El-S.E.; El-Hallouty, S.M.; Fayad, W.; Mohamed, K.M.; El-Menshawi, B.S.; El-Subbagh, H.I. Non-classical antifolates, part 4. 5-(2-aminothiazol-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiols as a new class of DHFR inhibitors: Synthesis, biological evaluation and molecular modeling study. Eur. J. Med. Chem., 2013, 66, 135-145.
[10]
Cunha, E.F.; Ramalho, T.C.; Maia, R.E.; Fundao, I.D.; Janeiro, R.D.; Teodorico, C.R.; Ricardo, B.D. The search for new DHFR inhibitors: A review of patents, January 2001-February 2005. Expert Opin. Ther. Pat., 2005, 15(8), 967-986.
[11]
Yaseen, G.; Jadhav, S. Design, synthesis and antimicrobial activity of 2-mercaptobenzimidazole derivatives. Int. J. Pharma Bio Sci., 2010, 1(4), 281-286.
[12]
Lam, T.; Hilgers, M.T.; Cunningham, M.L.; Bryan, P.K.; Kirk, J.N.; Vickie, B.D.; Voon, O.; Michael, T.; Grayson, H.; Karen, J.Y.S.; John, F. Structure based design of new dihydrofolate reductase antibacterial agents: 7-(Benzimidazol-1yl)-2,4-diamino-quinazolines. J. Med. Chem., 2014, 57(3), 651-668.
[13]
Ohmeng, K.A.; Barbara, R. Receptor based design of novel dihydrofolate reductase inhibitors; benzimidazole and indole derivatives. J. Med. Chem., 1991, 34(4), 1383-1394.
[14]
Jing, X.; Zhu, Q.; Xu, F.; Ren, X.; Li, D.; Yan, C. Rapid one-pot preparation of 2-substituted benzimidazoles from esters using microwave conditions. Synth. Commun., 2006, 36, 2597-2602.
[15]
Tandon, V.K.; Kumar, M. BF3Et2 promoted one-pot expeditious and convenient synthesis of 2-substituted benzimidazoles and 3,1,5-benzoxadiazepines. Tetrahedron Lett., 2004, 45, 4185-4191.
[16]
Balalaie, S.; Hashemi, M.M.; Akhbari, M. A novel one-pot synthesis of tetrasubstituted imidazoles under solvent free conditions and microwave irradiation. Tetrahedron Lett., 2003, 44(8), 1709-1711.
[17]
Rastogi, R.; Sharma, S. 2-amino benzimidazoles in organic synthesis. Synthesis, 1983, 861-866.
[18]
Van Vliet, D.S.; Gillespie, P.; Scicinski, J. Rapid one-pot preparation of 2-substituted benzimidazoles from 2-nitroanilines using microwave conditions. Tetrahedron Lett., 2005, 46, 6741-6746.
[19]
Hegedus, A.; Hell, Z.; Potor, A. Zeolite-catalyzed environmentally friendly synthesis of benzimidazole derivatives. Synth. Commun., 2006, 36, 3625-3635.
[20]
Lin, A.Y.; Isome, Y.; Stewart, E.; Liu, J.F.; Yohannes, D.; Yu, L. Microwave-assisted one step high-throughput synthesis of benzimidazoles. Tetrahedron Lett., 2006, 47, 2883-2892.
[21]
Bastien, D.; Ebert, M.C.C.J.C.; Forge, D.; Toulouse, J.; Kadnikova, N.; Perron, F.; Mayence, A.; Huang, T.L.; Eynde, J.V.; Pelletier, J.N. Fragment-based design of symmetrical bis-benzimidazoles as selective inhibitors of the trimethoprim-resistant, type II R67 dihydrofolate reductase. J. Med. Chem., 2012, 55(7), 3182-3192.
[22]
Savel, J.; Durand, R. Dihydrofolate reductase inhibitors: New developments in antiparasitic chemotherapy. Expert Opin. Ther. Pat., 2001, 11(8), 1285-1290.
[23]
Yuthavonga, Y.; Tarnchompooa, B.; Vilaivanb, T. Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target. Proc. Natl. Acad. Sci., 2012, 109(42), 16823-16828.
[24]
Kisliuk, R.L. The biochemistry of folates. In: Sirotnak, F.M.; Ensminger, W.D.; Burchall, J.J.; Montgomery, J.A. (Eds). Folate antagonists as therapeutic agents; New York: Academic Press. Sirotnak, F.M. John Wiley and Sons, New York, 1984, Vol. 1, pp. 1- 55.
[25]
Adane, L.; Bhagat, S.; Arfeen, M. Design and synthesis of guanylthiourea derivatives as potential inhibitors of Plasmodium falciparum dihydrofolate reductase enzyme. Bioorg. Med. Chem. Lett., 2014, 24, 613-617.
[26]
Al-Rashood, S.T.; Hassan, S.G.; El-Messery, S.M.; Nagi, M.N.; Habib, E.E.; Al-Omary, F.A.M.; El-Subbagh, H.I. Synthesis, biological evaluation and molecular modeling study of 2-(1,3,4-thiadiazolyl-thio and 4-methyl-thiazolyl-thio)-quinazolin-4-ones as a new class of DHFR inhibitors. Bioorg. Med. Chem. Lett., 2014, 24, 4557-4567.
[27]
Blaney, J.M.; Hansch, C.; Silipo, C.; Vittoria, A. Structure activity relationship of dihydrofolate reductase inhibitors. Chem. Rev., 1984, 84, 333-407.
[28]
Schrodinger, L.L.C. (Maestro, version 10.2). New York, 2015.
[29]
El-Hamamsy, M.H.; Smith, A.W.; Thompson, A.S.; Threadgill, M.D. Structure based design, synthesis and preliminary evaluation of selective inhibitors of dihydrofolate reductase from Mycobacterium tuberculosis. Bioorg. Med. Chem., 2007, 15, 4552-4576.
[30]
Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The protein data bank. Nucleic Acids Res., 2000, 28, 235-242.
[31]
Goncalves, A.D.; França, T.C.C.; Caetano, M.S.; Ramalho, T.C. Reactivation steps by 2-PAM of tabun-inhibited human acetylcholinesterase: Reducing the computational cost in hybrid QM/MM methods. J. Biomol. Struct. Dyn., 2014, 32(2), 301-307.
[32]
Jimonet, P.; Audiau, F.; Barreau, M.; Blanchard, J.C.; Boireau, A.; Bour, Y.; Coleno, M.A.; Doble, A.; Doerflinger, G.; Huu, C.D.; Donat, M.H.; Duchesne, J.M.; Ganil, P.; Gueremy, C.; Honore, E.; Just, B.; Kerphirique, R.; Gontier, S.; Hubert, P.; Laduron, P.M.; Blevec, J.L.; Meunier, M.; Miquet, J.M.; Nemecek, C.; Pasquet, M.; Piot, O.; Pratt, J.; Rataud, J.; Reibaud, M.; Stutzmann, J.M.; Mignani, S. Riluzole series: Synthesis and in vivo “Antiglutamate” activity of 6-substituted-2-benzothiazolamines and 3-substituted-2-imino-benzothiazolines. J. Med. Chem., 1999, 42(15), 2828-2843.
[33]
Tumelty, D.; Schwarz, M.K.; Needels, M.C. Solid phase synthesis of substituted benzimidazoles. Tetrahedron Lett., 1998, 39, 7467-7470.
[34]
Schuerman, R.A.; Tumelty, D. The reduction of aromatic nitro groups on solid supports using sodiumhydrosulfite (Na2S2O4). Tetrahedron Lett., 2000, 41, 6531-6535.
[35]
Bates, D.; Xia, M.J. A sulfoxide-based ring annelation approach to fused, many-membered ring N,S-heterocycles. Org. Chem., 1998, 63, 9190-9196.
[36]
Levai, A. Process for preparing 1,4-benzothiazepine derivatives. Pharmazie, 1980, 35, 680-681.
[37]
Bellamy, F.D.; Ou, K. Selective reduction of aromatic nitro compounds with stannous chloride in non acidic and non aqueous medium. Tetrahedron Lett., 1984, 25, 839-842.
[38]
Kugita, H.; Inoue, H.; Ikezaki, M.; Takeo, S. Novel reactions of nitroarenylketones with SnCl2. Chem. Pharm. Bull., 1970, 18, 2028-2037.
[39]
Hawser, S.; Lociuro, S.; Islam, K. Dihydrofolate reductase inhibitors as antibacterial agents. Biochem. Pharmacol., 2006, 71, 941-948.
[40]
Lin, G.L.; Ednie, M.; Clark, C.; Smith, K.; Kosowska-Shick, S.; McGhee, P.; Dewasse, B.; Beachel, L.; Caspers, P.; Gaucher, B.; Mert, G.; Shapiro, S.; Appelbaum, P.C. Antistaphylococcal activities of dihydrophthalazine dihydrofolates, a family of novel antibacterial drugs by time-kill, abstract F1-3937. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents Chemother. (ICAAC).
[41]
Peppard, W.J.; Schuenke, C.D. Iclaprim, a diaminopyrimidine dihydrofolate reductase inhibitor for the potential treatment of antibiotic resistant staphylococcal infections. Curr. Opin. Investig. Drugs, 2008, 9, 210-225.
[42]
Collins, C.H. Microbiological methods; Butterworths: London, 1964, p. 92.
[43]
Lorian, V. Antibiotics in laboratory medicine; Williams and Wikins: Baltimore, London, 1980, p. 1014.
[44]
CLSI approved standards M100-S15. Performance standards for antimicrobial susceptibility testing; clinical and laboratory standards institute; CLSI: Wayne, PA, 2008.
[45]
Wayne, P.A. CLSI approved standards M100-S15. Performance standards for antimicrobial susceptibility testing; clinical and laboratory standards institute; CLSI, 2008.
[46]
Murray, P.R.; Baron, E.J. Manual of clinical microbiology, 6th ed.; Washington, D.C: ASM Press, 2007.
[47]
Guven, O.O.; Erdogan, T.; Goker, H.; Yildiz, S. Synthesis and antimicrobial activity of some novel phenyl and benzimidazole substituted benzyl ethers. Bioorg. Med. Chem. Lett., 2007, 17, 2233-2236.
[48]
Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 6th ed.; Approved standard. Document M7- A6. Clinical and Laboratory Standards Institute, Wayne, PA, 2003.
[49]
Performance standards for antimicrobial susceptibility testing; 18th informational supplement. Document M100-S19, Clinical Laboratory Standards Institute, 2009.

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      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=50) and sj.journal_id!=50 group by `j`.`nid`) as `aggregate_table`
      1.73msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=50) and sj.journal_id!=50 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.4msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=50) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      2.09msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=50) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.93msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '96458'
      2.15msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 96458
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '96458'
      2.84msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 96458
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '96458' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.78msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 96458
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      270μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      570μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 50 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      62.45msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 50 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      35.75msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 50 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      16.15msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 96458 limit 1
      10.7msalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 96458
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 96458 and content_type = 'article' order by status desc limit 1
      2.61msalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 169727 limit 1
      770μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 169727
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      320μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'MC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      410μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: MC
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '96458' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      1.06msalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '9309' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      490μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '2528' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      470μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740774066 and j.to_date >= 1740774066 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2528) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740774066 and j.to_date >= 1740774066 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2528) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740774066 and j.to_date >= 1740774066 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2528)
      154msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740774066 and j.to_date >= 1740774066 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9309) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740774066 and j.to_date >= 1740774066 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9309) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740774066 and j.to_date >= 1740774066 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9309)
      3.69msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740774066 and j.to_date >= 1740774066 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 96458) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740774066 and j.to_date >= 1740774066 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 96458) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740774066 and j.to_date >= 1740774066 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 96458)
      1.52msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '813' and is_uploaded = 1 and issue_id = 9309 order by cast(first_page as SIGNED) desc limit 1
      1.14msalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 813
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '832' and is_uploaded = 1 and issue_id = 9309 order by cast(first_page as SIGNED) asc limit 1
      550μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 832
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      260μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      310μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 96458 limit 1
      3.74msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 96458
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 50 and `b`.`banner_from_date` <= 1740774066 and `b`.`banner_to_date` >= 1740774066 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.62msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 50
      • 3: 1740774066
      • 4: 1740774066
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 50 and `b`.`banner_from_date` <= 1740774066 and `b`.`banner_to_date` >= 1740774066 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.95msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 50
      • 3: 1740774066
      • 4: 1740774066
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='53c91e3584ebe381356e69b527942fed'
      370μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:291
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-28 20:21:06GET/article/96458314361