Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

In Vitro and In Silico Determination of Some N-ferrocenylmethylaniline Derivatives as Anti-Proliferative Agents Against MCF-7 Human Breast Cancer Cell Lines

Author(s): Nadjiba Zegheb, Cherifa Boubekri, Touhami Lanez*, Elhafnaoui Lanez, Tuba Tüylü Küçükkılınç, Esin Öz, Ali Khennoufa, Saida Khamouli and Salah Belaidi

Volume 22, Issue 7, 2022

Published on: 03 January, 2022

Page: [1426 - 1437] Pages: 12

DOI: 10.2174/1871520621666210624141712

Price: $65

Abstract

Background: Since the binding of estradiol to its receptor promotes breast cancer cell proliferation (in the ER+ tumours), many molecules targeting this protein have been synthesized to counteract the estradiol action. Ferrocene derivatives have proved their efficiency against hormone-dependent breast cancer cells (MCF-7).

Objective: In this study, we aimed to find new ferrocene derivatives having pharmacochemistry properties as potential drugs against human breast cancer cells.

Methods: A series of 29 N-ferrocenylmethylaniline derivatives A0-A28 were synthesised, and their anti-proliferative activity against both hormone-dependent (MCF-7) and independent (MDA-MB 231) human breast cancer cell lines were performed using the MTT test. Molecular docking and drug-likeness prediction were also performed for the five most active derivatives towards MCF-7. A QSAR model was also developed for the perdition of the anti-proliferative activity against MCF-7 cell lines using molecular descriptors and MLR analysis.

Results: All studied derivatives demonstrated better cytotoxicity against MCF-7 compared to the MDA-MB-231 cell lines, and compounds A2, A9, A14, A17 and A27 were the most potent ones but still less active than the standard anticancer drug, crizotinib. The QSAR study revealed good predictive ability, as shown by R2 cv = 0.848.

Conclusion: In vitro and in silico results indicated that derivatives A2, A9, A14, A17, and A27 possess the highest anti-proliferative activity; these results can be used to design more potent N-ferrocenylmethylaniline derivatives as anti-proliferative agents.

Keywords: N-ferrocenylmethylaniline, breast cancer, MCF-7, MDA-MB-231, estrogen receptor, progesterone receptor, QSAR, antiproliferative activity.

« Previous
Graphical Abstract

[1]
World Health Organization Cancer fact sheets, Available from: http://gco.iarc.fr/today/fact-sheets-cancers[Accessed November 10, 2020]
[2]
Jéhannin-Ligier, K.; Dantony, E.; Bossard, N.; Molinié, F.; Defossez, G.; Daubisse-Marliac, L.; Delafosse, P.; Remontet, L.; Uhry, Z. Projection de l’incidence et de la mortalité par cancer en France métropolitaine en 2017.Rapport technique; Saint-Maurice: Santé publique France, 2017.
[3]
American Cancer Society Breast cancer, Available from: https://www.cancer.org/cancer/breast-cancer.html[Accessed November 10, 2020]
[4]
Hudis, C.A. Trastuzumab--mechanism of action and use in clinical practice. N. Engl. J. Med., 2007, 357(1), 39-51.
[http://dx.doi.org/10.1056/NEJMra043186] [PMID: 17611206]
[5]
Ismael, G.; Rosa, D.D.; de Azambuja, E.; Braga, S.; Piccart-Gebhart, M. Trastuzumab (herceptin) for early-stage breast cancer. Hematol. Oncol. Clin. North Am., 2007, 21(2), 239-256.
[http://dx.doi.org/10.1016/j.hoc.2007.03.003] [PMID: 17512447]
[6]
Wang, J.; Xu, B. Targeted therapeutic options and future perspectives for HER2-positive breast cancer. Signal Transduct. Target. Ther., 2019, 4(1), 34.
[http://dx.doi.org/10.1038/s41392-019-0069-2] [PMID: 31637013]
[7]
Hortobagyi, G.N.; Buzdar, A.U. Current status of adjuvant systemic therapy for primary breast cancer: Progress and controversy. CA Cancer J. Clin., 1995, 45(4), 199-226.
[http://dx.doi.org/10.3322/canjclin.45.4.199] [PMID: 7600278]
[8]
Group, E.B.C.T.C. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet, 2005, 365(9472), 1687-1717.
[http://dx.doi.org/10.1016/S0140-6736(05)66544-0] [PMID: 15894097]
[9]
Gong, Z.; Chen, M.; Ren, Q.; Yue, X.; Dai, Z. Fibronectin-targeted dual-acting micelles for combination therapy of metastatic breast cancer. Signal Transduct. Target. Ther., 2020, 5(1), 12.
[http://dx.doi.org/10.1038/s41392-019-0104-3] [PMID: 32296050]
[10]
Jordan, V.C. Antiestrogens and selective estrogen receptor modulators as multifunctional medicines. 2. Clinical considerations and new agents. J. Med. Chem., 2003, 46(7), 1081-1111.
[http://dx.doi.org/10.1021/jm020450x] [PMID: 12646017]
[11]
Singh, M.N.; Stringfellow, H.F.; Paraskevaidis, E.; Martin-Hirsch, P.L.; Martin, F.L. Tamoxifen: Important considerations of a multi-functional compound with organ-specific properties. Cancer Treat. Rev., 2007, 33(2), 91-100.
[http://dx.doi.org/10.1016/j.ctrv.2006.09.008] [PMID: 17178195]
[12]
Dixon, J.M. Exemestane and aromatase inhibitors in the management of advanced breast cancer. Expert Opin. Pharmacother., 2004, 5(2), 307-316.
[http://dx.doi.org/10.1517/14656566.5.2.307] [PMID: 14996627]
[13]
Meegan, M.J.; Lloyd, D.G. Advances in the science of estrogen receptor modulation. Curr. Med. Chem., 2003, 10(3), 181-210.
[http://dx.doi.org/10.2174/0929867033368501] [PMID: 12570707]
[14]
Magarian, R.; Overacre, L.; Singh, S.; Meyer, K. The medicinal chemistry of nonsteroidal antiestrogens: A review. Curr. Med. Chem., 1994, 1, 61-104.
[15]
American Cancer Society. Treating breast cancer, Available from: https://www.cancer.org/cancer/breast-cancer/treatment.html[Accessed November 10, 2020]
[16]
Köpf-Maier, P.; Köpf, H.; Neuse, E.W. Ferricenium complexes: A new type of water-soluble antitumor agent. J. Cancer Res. Clin. Oncol., 1984, 108(3), 336-340.
[http://dx.doi.org/10.1007/BF00390468] [PMID: 6511806]
[17]
Köpf-Maier, P. Tumor inhibition by ferricenium complexes: Systemic effect in vivo and cell growth inhibition in vitro. Z Naturforsch C Biosci, 1985, 40(11-12), 843-846.
[http://dx.doi.org/10.1515/znc-1985-11-1215] [PMID: 3832667]
[18]
Vessières, A.; Top, S.; Pigeon, P.; Hillard, E.; Boubeker, L.; Spera, D.; Jaouen, G. Modification of the estrogenic properties of diphenols by the incorporation of ferrocene. Generation of antiproliferative effects in vitro. J. Med. Chem., 2005, 48(12), 3937-3940.
[http://dx.doi.org/10.1021/jm050251o] [PMID: 15943467]
[19]
Hillard, E.; Vessières, A.; Le Bideau, F.; Plazuk, D.; Spera, D.; Huché, M.; Jaouen, G. A series of unconjugated ferrocenyl phenols: Prospects as anticancer agents. ChemMedChem, 2006, 1(5), 551-559.
[http://dx.doi.org/10.1002/cmdc.200500035] [PMID: 16892391]
[20]
Khand, I.U.; Lanez, T.; Pauson, P.L. Ferrocene derivatives. Part 24. Synthesis of dihydro-2-pyrindines and dihydro-3H-2-cyclopent[c]azepines by photolysis of their cyclopentadienyliron derivatives. J. Chem. Soc., Perkin Trans. 1, 1989, 2075-2078.
[http://dx.doi.org/10.1039/p19890002075]
[21]
Boubekri, C.; Khelef, A.; Terki, B.; Lanez, T. Synthesis and electrochemical properties of n-(ferrocenylmethyl)aminobenzonitrile and n-(ferrocenylmethyl)nitroaniline derivatives. ILCPA, 2015, 49, 27-34.
[http://dx.doi.org/10.18052/www.scipress.com/ILCPA.49.27]
[22]
Lanez, E.; Bechki, L.; Lanez, T. N6,9-bis(ferrocenylmethyl)adenine: Synthesis, cyclic voltammetric, spectroscopic characterization, and DFT calculations. St. Cerc. St. CICBIA, 2019, 20(4), 509-519.
[23]
Khelef, A.; Terki, B.; Mahboub, M.S.; Lanez, T. N-Ferrocenymethyl-N-phenylpropionamide. Acta Crystallogr., 2012, E68, m647.
[24]
Lanez, E.; Bechki, L.; Lanez, T. Ferrocenylmethylnucleobases: Synthesis, DFT calculations, electrochemical and spectroscopic characterisation. Chem. Chem. Technol, 2020, 14(2), 146-153.
[http://dx.doi.org/10.23939/chcht14.02.146]
[25]
Becke, A.D. Density-functional thermochemistry. III. The role of exact exchange. J. Chem. Phys., 1993, 98(7), 5648-5652.
[http://dx.doi.org/10.1063/1.464913]
[26]
Miehlich, B. Results obtained with the correlation energy density functionals of Becke and Lee, Yang and Parr. Chem. Phys. Lett., 1989, 157(3), 200-206.
[http://dx.doi.org/10.1016/0009-2614(89)87234-3]
[27]
Frisch, M. Gaussian 09; Gaussian, Inc.: Wallingford, CT, 2009.
[28]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[29]
Dykstra, K.D.; Guo, L.; Birzin, E.T.; Chan, W.; Yang, Y.T.; Hayes, E.C.; DaSilva, C.A.; Pai, L.Y.; Mosley, R.T.; Kraker, B.; Fitzgerald, P.M.; DiNinno, F.; Rohrer, S.P.; Schaeffer, J.M.; Hammond, M.L. Estrogen receptor ligands. Part 16: 2-Aryl indoles as highly subtype selective ligands for ERalpha. Bioorg. Med. Chem. Lett., 2007, 17(8), 2322-2328.
[http://dx.doi.org/10.1016/j.bmcl.2007.01.054] [PMID: 17289385]
[30]
Williams, S.P.; Sigler, P.B. Atomic structure of progesterone complexed with its receptor. Nature, 1998, 393(6683), 392-396.
[http://dx.doi.org/10.1038/30775] [PMID: 9620806]
[31]
Systèmes, D. Biovia discovery studio modeling environment; Dassault Systèmes Biovia: San Diego, CA, USA, 2016.
[32]
Darwin, K.H.; Ehrt, S.; Gutierrez-Ramos, J.C.; Weich, N.; Nathan, C.F. The proteasome of mycobacterium tuberculosis is required for resistance to nitric oxide. Science, 2003, 302(5652), 1963-1966.
[http://dx.doi.org/10.1126/science.1091176] [PMID: 14671303]
[33]
Bandyopadhyay, N.; Pradhan, A.B.; Das, S.; Lu, L.; Zhu, M.; Chowdhury, S.; Naskar, J.P. Synthesis, structure, DFT calculations, electrochemistry, fluorescence, DNA binding and molecular docking aspects of a novel oxime based ligand and its palladium(II) complex. J. Photochem. Photobiol. B, 2016, 160, 336-346.
[http://dx.doi.org/10.1016/j.jphotobiol.2016.04.026] [PMID: 27179300]
[34]
Guhathakurta, B. Synthesis, characterization, structure, DNA binding aspects and molecular docking study of a novel Schiff base ligand and its bis (μ-chloro) bridged Cu (II) dimer. Polyhedron, 2017, 126, 195-204.
[http://dx.doi.org/10.1016/j.poly.2017.01.033]
[35]
Salentin, S.; Schreiber, S.; Haupt, V.J.; Adasme, M.F.; Schroeder, M. PLIP: Fully automated protein-ligand interaction profiler. Nucleic Acids Res., 2015, 43(W1), W443-7.
[http://dx.doi.org/10.1093/nar/gkv315] [PMID: 25873628]
[36]
Daina, A.; Michielin, O.; Zoete, V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7, 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[37]
Daina, A.; Michielin, O.; Zoete, V. iLOGP: A simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. J. Chem. Inf. Model., 2014, 54(12), 3284-3301.
[http://dx.doi.org/10.1021/ci500467k] [PMID: 25382374]
[38]
Teppen, B.J. HyperChem, release 2: Molecular modeling for the personal computer. J. Chem. Inf. Comput. Sci., 1992, 32(6), 757-759.
[http://dx.doi.org/10.1021/ci00010a025]
[39]
Purkayastha, S.K.; Jha, T.; Pal, D.K.; De, A.U. Possible antineoplastic agents: Part XIII. Synthesis, biological evaluation and QSAR studies of some 1-(substituted benzenesulphonyl)-5-oxopyrrolidine-2-carboxylic acid derivatives. Anticancer Drug Des., 1993, 8(2), 95-100.
[PMID: 8494605]
[40]
Srikanth, K. As a part of a composite programme of rational drug design (RDD)', we had synthesized some substituted. Indian J. Biochem. Biophys., 2001, 38, 120.
[PMID: 11563323]
[41]
Srikanth, K.; Debnath, B.; Jha, T. QSAR study on adenosine kinase inhibition of pyrrolo[2,3-d]pyrimidine nucleoside analogues using the hansch approach. Bioorg. Med. Chem. Lett., 2002, 12(6), 899-902.
[http://dx.doi.org/10.1016/S0960-894X(02)00042-2] [PMID: 11958989]
[42]
Jha, T. QSAR study on some substituted glutamine analogs as anticancer agents. Internet Electron. J. Mol. Des, 2003, 2, 539-545.
[43]
Samanta, S.; Srikanth, K.; Banerjee, S.; Debnath, B.; Gayen, S.; Jha, T. 5-N-Substituted-2-(substituted benzenesulphonyl) glutamines as antitumor agents. Part II: Synthesis, biological activity and QSAR study. Bioorg. Med. Chem., 2004, 12(6), 1413-1423.
[http://dx.doi.org/10.1016/j.bmc.2004.01.006] [PMID: 15018914]
[44]
Vladusic, E.A.; Hornby, A.E.; Guerra-Vladusic, F.K.; Lupu, R. Expression of estrogen receptor β messenger RNA variant in breast cancer. Cancer Res., 1998, 58(2), 210-214.
[PMID: 9443393]
[45]
Brzozowski, A.M.; Pike, A.C.; Dauter, Z.; Hubbard, R.E.; Bonn, T.; Engström, O.; Ohman, L.; Greene, G.L.; Gustafsson, J.A.; Carlquist, M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature, 1997, 389(6652), 753-758.
[http://dx.doi.org/10.1038/39645] [PMID: 9338790]
[46]
Mordasini, T.; Curioni, A.; Bursi, R.; Andreoni, W. The binding mode of progesterone to its receptor deduced from molecular dynamics simulations. ChemBioChem, 2003, 4(2-3), 155-161.
[http://dx.doi.org/10.1002/cbic.200390026] [PMID: 12616628]
[47]
Tanenbaum, D.M.; Wang, Y.; Williams, S.P.; Sigler, P.B. Crystallographic comparison of the estrogen and progesterone receptor’s ligand binding domains. Proc. Natl. Acad. Sci. USA, 1998, 95(11), 5998-6003.
[http://dx.doi.org/10.1073/pnas.95.11.5998] [PMID: 9600906]
[48]
Alam, S.; Khan, F. 3D-QSAR, Docking, ADME/Tox studies on Flavone analogs reveal anticancer activity through Tankyrase inhibition. Sci. Rep., 2019, 9(1), 5414.
[http://dx.doi.org/10.1038/s41598-019-41984-7] [PMID: 30932078]
[49]
Jalali-Heravi, M.; Kyani, A. Use of computer-assisted methods for the modeling of the retention time of a variety of volatile organic compounds: A PCA-MLR-ANN approach. J. Chem. Inf. Comput. Sci., 2004, 44(4), 1328-1335.
[http://dx.doi.org/10.1021/ci0342270] [PMID: 15272841]
[50]
Podunavac-Kuzmanović, S.O.; Cvetković, D.D.; Barna, D.J. QSAR analysis of 2-amino or 2-methyl-1-substituted benzimidazoles against Pseudomonas aeruginosa. Int. J. Mol. Sci., 2009, 10(4), 1670-1682.
[http://dx.doi.org/10.3390/ijms10041670] [PMID: 19468332]
[51]
Srivastava, A.; Shukla, N. Quantitative structure activity relationship (QSAR) studies on a series of imidazole derivatives as novel ORL1 receptor antagonists. J. Saudi Chem. Soc., 2013, 17(3), 321-328.
[http://dx.doi.org/10.1016/j.jscs.2011.04.014]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version332msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[23:30:13] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[23:30:13] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[23:30:13] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[23:30:13] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (148ms)time
  • Application (184ms)time
  • 1 x Application (55.33%)
    184ms
    1 x Booting (44.67%)
    148ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated101ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('316303896','',1,1740526213,1740526213) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740526213
      1.25msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('316303896','/article/116321',1,1740526213,1740526213)
      150μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) limit 1
      13.75msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316303896
      • 1: 316303896
      • 2: 316303896
      • 3: 316303896
      • 4: 316303896
      • 5: 316303896
      • 6: 316303896
      • 7: 316303896
      • 8: 316303896
      • 9: 316303896
      • 10: 316303896
      • 11: 316303896
      • 12: 316303896
      • 13: 316303896
      • 14: 316303896
      • 15: 316303896
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=116321
      710μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 1 limit 1
      780μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 1
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 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=1) and sj.journal_id!=1 group by `j`.`nid`) as `aggregate_table`
      1.19msalphaeurekaselec_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=1) and sj.journal_id!=1 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      950μsalphaeurekaselec_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=1) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      3.04msalphaeurekaselec_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=1) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.54msalphaeurekaselec_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` = '116321'
      1.13msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 116321
      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` = '116321'
      4.02msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 116321
      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` = '116321' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.99msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 116321
      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
      220μsalphaeurekaselec_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
      420μsalphaeurekaselec_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 = 1 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      25.42msalphaeurekaselec_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 = 1 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      13.56msalphaeurekaselec_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 = 1 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      12.16msalphaeurekaselec_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` = 116321 limit 1
      720μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 116321
      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 = 116321 and content_type = 'article' order by status desc limit 1
      280μsalphaeurekaselec_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` = 194259 limit 1
      210μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 194259
      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
      190μsalphaeurekaselec_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` = 'ACAMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      270μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: ACAMC
      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 = '116321' 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) )
      340μsalphaeurekaselec_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 = '11336' 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) )
      290μsalphaeurekaselec_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 = '3166' 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) )
      240μsalphaeurekaselec_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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526213 and j.to_date >= 1740526213 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3166) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526213 and j.to_date >= 1740526213 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3166) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526213 and j.to_date >= 1740526213 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3166)
      6.67msalphaeurekaselec_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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526213 and j.to_date >= 1740526213 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11336) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526213 and j.to_date >= 1740526213 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11336) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526213 and j.to_date >= 1740526213 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11336)
      560μsalphaeurekaselec_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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526213 and j.to_date >= 1740526213 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 116321) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526213 and j.to_date >= 1740526213 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 116321) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526213 and j.to_date >= 1740526213 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 116321)
      530μsalphaeurekaselec_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` < '1426' and is_uploaded = 1 and issue_id = 11336 order by cast(first_page as SIGNED) desc limit 1
      540μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 1426
      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` > '1437' and is_uploaded = 1 and issue_id = 11336 order by cast(first_page as SIGNED) asc limit 1
      410μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 1437
      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'
      160μsalphaeurekaselec_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
      170μsalphaeurekaselec_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` = 116321 limit 1
      2.3msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 116321
      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` = 1 and `b`.`banner_from_date` <= 1740526213 and `b`.`banner_to_date` >= 1740526213 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.15msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1740526213
      • 4: 1740526213
      • 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` = 1 and `b`.`banner_from_date` <= 1740526213 and `b`.`banner_to_date` >= 1740526213 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.11msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1740526213
      • 4: 1740526213
      • 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='dd150615556bfe38128e9dc80d9703e7'
      200μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 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#?
        _token
        vccTda7a2N2efl3lmPumcYQy77ukhQ7ptlrUJzwT
        uc_cart_id
        dd150615556bfe38128e9dc80d9703e7
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/116321" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/116321
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 23:30:13 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlY3b2lQV1BxVWJWY3NaV2JaSFdGNWc9PSIsInZhbHVlIjoiVWl1U0VrcHR3Q05BaWtoYTFwZDhwVUxRTU5oejM5YnZDVjlWdGJ4ZVptM1cxU25vSGladDJsN1hBSUQ4TXNLSjB4c1dHSXFZQTBYTU5lU3F5SHFuZDVPVWEwKzVCU1hZVzBvcXd2TUV2V0pXMkFqWXVka1JDeWtkVjBCaUxiN28iLCJtYWMiOiI2YjZjYjZmY2MxMmRhMzdjNzcxNWU1YzViNGZmYjAwMjZiODY1ZTc0ZmE3MjJmYTYxMGU1ZWIxMDlmZWQ0MDMzIiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 11:30:13 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IlY3b2lQV1BxVWJWY3NaV2JaSFdGNWc9PSIsInZhbHVlIjoiVWl1U0VrcHR3Q05BaWtoYTFwZDhwVUxRTU5oejM5YnZDVjlWdGJ4ZVptM1cxU25vSGladDJsN1hBSUQ4TXNLSjB4c1dHS" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkY1QTUxVUI0eE9nSW15Z2dtQytleVE9PSIsInZhbHVlIjoiLzcxYWhwclM5ZzFhMU5wTHM4RXBBZXZaQUVBQWdGOHNWRFJmTXpSb1ExQkU0dUhiM1liS1JsTlRLekNpSG5wY1Jhc3g0QkUxbk5LR2xVd3B6YXZ5QnNFV3pPcmtGVkxNL25jMWJBMW1LK0JUeXlKVlBaeFVEYVdtNlVDNHlCOXEiLCJtYWMiOiIwNDEwOGQ2ZjRmMjAxODkwNGYzOTk3Mjk0ZTkxYzM1ZmNhNGY3NmI0MzA4NzdjNjM1YjRhNWFiN2Q0MDBmMGNiIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IkY1QTUxVUI0eE9nSW15Z2dtQytleVE9PSIsInZhbHVlIjoiLzcxYWhwclM5ZzFhMU5wTHM4RXBBZXZaQUVBQWdGOHNWRFJmTXpSb1ExQkU0dUhiM1liS1JsTlR" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlY3b2lQV1BxVWJWY3NaV2JaSFdGNWc9PSIsInZhbHVlIjoiVWl1U0VrcHR3Q05BaWtoYTFwZDhwVUxRTU5oejM5YnZDVjlWdGJ4ZVptM1cxU25vSGladDJsN1hBSUQ4TXNLSjB4c1dHSXFZQTBYTU5lU3F5SHFuZDVPVWEwKzVCU1hZVzBvcXd2TUV2V0pXMkFqWXVka1JDeWtkVjBCaUxiN28iLCJtYWMiOiI2YjZjYjZmY2MxMmRhMzdjNzcxNWU1YzViNGZmYjAwMjZiODY1ZTc0ZmE3MjJmYTYxMGU1ZWIxMDlmZWQ0MDMzIiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 11:30:13 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IlY3b2lQV1BxVWJWY3NaV2JaSFdGNWc9PSIsInZhbHVlIjoiVWl1U0VrcHR3Q05BaWtoYTFwZDhwVUxRTU5oejM5YnZDVjlWdGJ4ZVptM1cxU25vSGladDJsN1hBSUQ4TXNLSjB4c1dHS" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkY1QTUxVUI0eE9nSW15Z2dtQytleVE9PSIsInZhbHVlIjoiLzcxYWhwclM5ZzFhMU5wTHM4RXBBZXZaQUVBQWdGOHNWRFJmTXpSb1ExQkU0dUhiM1liS1JsTlRLekNpSG5wY1Jhc3g0QkUxbk5LR2xVd3B6YXZ5QnNFV3pPcmtGVkxNL25jMWJBMW1LK0JUeXlKVlBaeFVEYVdtNlVDNHlCOXEiLCJtYWMiOiIwNDEwOGQ2ZjRmMjAxODkwNGYzOTk3Mjk0ZTkxYzM1ZmNhNGY3NmI0MzA4NzdjNjM1YjRhNWFiN2Q0MDBmMGNiIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IkY1QTUxVUI0eE9nSW15Z2dtQytleVE9PSIsInZhbHVlIjoiLzcxYWhwclM5ZzFhMU5wTHM4RXBBZXZaQUVBQWdGOHNWRFJmTXpSb1ExQkU0dUhiM1liS1JsTlR" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "vccTda7a2N2efl3lmPumcYQy77ukhQ7ptlrUJzwT" "uc_cart_id" => "dd150615556bfe38128e9dc80d9703e7" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/116321" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 23:30:13GET/article/116321414361