Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

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

Research Article

2-Substituted Benzoxazoles as Potent Anti-Inflammatory Agents: Synthesis, Molecular Docking and In vivo Anti-Ulcerogenic Studies

Author(s): Iqra Hamid, Humaira Nadeem*, Sameen Fatima Ansari, Sonia Khiljee, Inzamam Abbasi, Asma Bukhari, Muazzam Arif and Muhammad Imran*

Volume 18, Issue 7, 2022

Published on: 15 February, 2022

Page: [791 - 809] Pages: 19

DOI: 10.2174/1573406418666211220125344

Price: $65

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are the commonly used therapeutic interventions of inflammation and pain that competitively inhibit the cyclooxygenase (COX) enzymes. Several side effects like gastrointestinal and renal toxicities are associated with the use of these drugs. The therapeutic anti-inflammatory benefits of NSAIDs are produced by the inhibition of COX-2 enzymes, while undesirable side effects arise from the inhibition of COX-1 enzymes.

Objective: In the present study, a new series of 2-substituted benzoxazole derivatives 2(a-f) and 3(ae) were synthesized in our lab as potent anti-inflammatory agents with outstanding gastro-protective potential. The new analogs 2(a-f) and 3(a-e) were designed depending upon the literature review to serve as ligands for the development of selective COX-2 inhibitors.

Methods: The synthesized analogs were characterized using different spectroscopic techniques (FTIR, 1HNMR, 13CNMR) and elemental analysis. All synthesized compounds were screened for their binding potential in the protein pocket of COX-2 and evaluated for their anti-inflammatory potential in animals using the carrageenan-induced paw edema method. Further 5 compounds were selected to assess the in vivo anti-ulcerogenic activity in an ethanol-induced anti-ulcer rat model.

Results: Five compounds (2a, 2b, 3a, 3b and 3c) exhibited potent anti-inflammatory activity and significant binding potential in the COX-2 protein pocket. Similarly, these five compounds demonstrated a significant gastro-protective effect (**p<0.01) in comparison to the standard drug, Omeprazole.

Conclusion: Depending upon our results, we hypothesize that 2-substituted benzoxazole derivatives have excellent potential to serve as candidates for the development of selective anti-inflammatory agents (COX-2 inhibitors). However, further assessments are required to delineate their underlying mechanisms.

Keywords: 2-Substituted benzoxazole, anti-inflammatory, coxibs, COX-2 inhibitor, ethanol, docking.

Graphical Abstract

[1]
Firke, S.D.; Bari, S.B. Synthesis, biological evaluation and docking study of maleimide derivatives bearing benzenesulfonamide as selective COX-2 inhibitors and anti-inflammatory agents. Bioorg. Med. Chem., 2015, 23(17), 5273-5281.
[http://dx.doi.org/10.1016/j.bmc.2015.07.070] [PMID: 26277757]
[2]
Kaplan, A.P.; Joseph, K.; Silverberg, M. Pathways for bradykinin formation and inflammatory disease. J. Allergy Clin. Immunol., 2002, 109(2), 195-209.
[http://dx.doi.org/10.1067/mai.2002.121316] [PMID: 11842287]
[3]
Paramashivappa, R.; Phani Kumar, P.; Subba Rao, P.V.; Srinivasa Rao, A. Design, synthesis and bio-logical evaluation of benzimidazole/benzothiazole and benzoxazole derivatives as cyclooxygenase in-hibitors. Bioorg. Med. Chem. Lett., 2003, 13(4), 657-660.
[http://dx.doi.org/10.1016/S0960-894X(02)01006-5] [PMID: 12639552]
[4]
Simmons, D.L. What makes a good anti-inflammatory drug target? Drug Discov. Today, 2006, 11(5-6), 210-219.
[http://dx.doi.org/10.1016/S1359-6446(05)03721-9] [PMID: 16580598]
[5]
Murdoch, J.R.; Lloyd, C.M. Chronic inflammation and asthma. Mutat. Res., 2010, 690(1-2), 24-39.
[http://dx.doi.org/10.1016/j.mrfmmm.2009.09.005] [PMID: 19769993]
[6]
Scanzello, C.R. Role of low-grade inflammation in osteoarthritis. Curr. Opin. Rheumatol., 2017, 29(1), 79-85.
[http://dx.doi.org/10.1097/BOR.0000000000000353] [PMID: 27755180]
[7]
Dowlatshahi, E.A.; van der Voort, E.A.; Arends, L.R.; Nijsten, T. Markers of systemic inflammation in psoriasis: A systematic review and meta-analysis. Br. J. Dermatol., 2013, 169(2), 266-282.
[http://dx.doi.org/10.1111/bjd.12355] [PMID: 23550658]
[8]
Navarro-González, J.F.; Mora-Fernández, C.; Muros de Fuentes, M.; García-Pérez, J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat. Rev. Nephrol., 2011, 7(6), 327-340.
[http://dx.doi.org/10.1038/nrneph.2011.51] [PMID: 21537349]
[9]
Doupis, J.; Lyons, T.E.; Wu, S.; Gnardellis, C.; Dinh, T.; Veves, A. Microvascular reactivity and in-flammatory cytokines in painful and painless peripheral diabetic neuropathy. J. Clin. Endocrinol. Metab., 2009, 94(6), 2157-2163.
[http://dx.doi.org/10.1210/jc.2008-2385] [PMID: 19276232]
[10]
Said, G. Diabetic neuropathy-a review. Nat. Clin. Pract. Neurol., 2007, 3(6), 331-340.
[http://dx.doi.org/10.1038/ncpneuro0504] [PMID: 17549059]
[11]
Rakoff-Nahoum, S. Why cancer and inflammation? YJBM, 2006, 79(3-4), 123-130.
[PMID: 17940622]
[12]
Mantovani, A.; Allavena, P.; Sica, A.; Balkwill, F. Cancer-related inflammation. Nature, 2008, 454(7203), 436-444.
[http://dx.doi.org/10.1038/nature07205] [PMID: 18650914]
[13]
Marnett, L.J.; Rowlinson, S.W.; Goodwin, D.C.; Kalgutkar, A.S.; Lanzo, C.A. Arachidonic acid oxy-genation by COX-1 and COX-2. Mechanisms of catalysis and inhibition. J. Biol. Chem., 1999, 274(33), 22903-22906.
[http://dx.doi.org/10.1074/jbc.274.33.22903] [PMID: 10438452]
[14]
Arif, M.N.; Nadeem, H.; Paracha, R.Z. Khan, A-u.; Imran, M.; Ali, F. Synthesis, anti-inflammatory, antimicrobial potential and molecular docking studies of 4, 5-disubstituted-1, 2, 4-triazole thioacetate derivatives. Lett. Drug Des. Discov., 2019, 16(7), 734-745.
[http://dx.doi.org/10.2174/1570180815666180810122226]
[15]
Xie, W.L.; Chipman, J.G.; Robertson, D.L.; Erikson, R.L.; Simmons, D.L. Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc. Natl. Acad. Sci. USA, 1991, 88(7), 2692-2696.
[http://dx.doi.org/10.1073/pnas.88.7.2692] [PMID: 1849272]
[16]
Kujubu, D.A.; Fletcher, B.S.; Varnum, B.C.; Lim, R.W.; Herschman, H.R. TIS10, a phorbol ester tu-mor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin syn-thase/cyclooxygenase homologue. J. Biol. Chem., 1991, 266(20), 12866-12872.
[http://dx.doi.org/10.1016/S0021-9258(18)98774-0] [PMID: 1712772]
[17]
Hla, T.; Neilson, K. Human cyclooxygenase-2 cDNA. Proc. Natl. Acad. Sci. USA, 1992, 89(16), 7384-7388.
[http://dx.doi.org/10.1073/pnas.89.16.7384] [PMID: 1380156]
[18]
Unlü, S.; Baytas, S.N.; Kupeli, E.; Yesilada, E. Studies on novel 7- acyl-5-chloro-2-oxo-3H-benzoxazole derivatives as potential analgesic and anti-inflammatory agents. Arch. Pharm. (Weinheim), 2003, 336(6-7), 310-321.
[http://dx.doi.org/10.1002/ardp.200300748] [PMID: 12953219]
[19]
Gambaro, G.; Perazella, M.A. Adverse renal effects of antiinflammatory agents: evaluation of selective and nonselective cyclooxygenase inhibitors. J., 2003, 253(6), 643-652.
[20]
Mahdi, M.F.; Alsaad, H.N. Design, synthesis and hydrolytic behavior of mutual prodrugs of NSAIDs with gabapentin using glycol spacers. Pharmaceuticals (Basel), 2012, 5(10), 1080-1091.
[http://dx.doi.org/10.3390/ph5101080] [PMID: 24281258]
[21]
Masferrer, J.L.; Zweifel, B.S.; Manning, P.T.; Hauser, S.D.; Leahy, K.M.; Smith, W.G.; Isakson, P.C.; Seibert, K. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and non-ulcerogenic. Proc. Natl. Acad. Sci. USA, 1994, 91(8), 3228-3232.
[http://dx.doi.org/10.1073/pnas.91.8.3228] [PMID: 8159730]
[22]
Bombardier, C.; Laine, L.; Reicin, A.; Shapiro, D.; Burgos-Vargas, R.; Davis, B.; Day, R.; Ferraz, M.B.; Hawkey, C.J.; Hochberg, M.C.; Kvien, T.K.; Schnitzer, T.J. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N. Engl. J. Med., 2000, 343(21), 1520-1528, 2, 1528.
[http://dx.doi.org/10.1056/NEJM200011233432103] [PMID: 11087881]
[23]
Mukherjee, D.; Nissen, S.E.; Topol, E.J. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA, 2001, 286(8), 954-959.
[http://dx.doi.org/10.1001/jama.286.8.954] [PMID: 11509060]
[24]
Bertagnolli, M.M.; Eagle, C.J.; Zauber, A.G.; Redston, M.; Solomon, S.D.; Kim, K.; Tang, J.; Rosen-stein, R.B.; Wittes, J.; Corle, D.; Hess, T.M.; Woloj, G.M.; Boisserie, F.; Anderson, W.F.; Viner, J.L.; Bagheri, D.; Burn, J.; Chung, D.C.; Dewar, T.; Foley, T.R.; Hoffman, N.; Macrae, F.; Pruitt, R.E.; Saltzman, J.R.; Salzberg, B.; Sylwestrowicz, T.; Gordon, G.B.; Hawk, E.T. Celecoxib for the preven-tion of sporadic colorectal adenomas. N. Engl. J. Med., 2006, 355(9), 873-884.
[http://dx.doi.org/10.1056/NEJMoa061355] [PMID: 16943400]
[25]
Solomon, S.D.; Wittes, J.; Finn, P.V.; Fowler, R.; Viner, J.; Bertagnolli, M.M.; Arber, N.; Levin, B.; Meinert, C.L.; Martin, B.; Pater, J.L.; Goss, P.E.; Lance, P.; Obara, S.; Chew, E.Y.; Kim, J.; Arndt, G.; Hawk, E. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: The cross tri-al safety analysis. Circulation, 2008, 117(16), 2104-2113.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.764530] [PMID: 18378608]
[26]
Dogné, J-M.; Supuran, C.T.; Pratico, D. Adverse cardiovascular effects of the coxibs. J. Med. Chem., 2005, 48(7), 2251-2257.
[http://dx.doi.org/10.1021/jm0402059] [PMID: 15801815]
[27]
Schneider, F.; Meziani, F.; Chartier, C.; Alt, M.; Jaeger, A. Fatal allergic vasculitis associated with celecoxib. Lancet, 2002, 359(9309), 852-853.
[http://dx.doi.org/10.1016/S0140-6736(02)07922-9] [PMID: 11897288]
[28]
Shono, T.; Tofilon, P.J.; Bruner, J.M.; Owolabi, O.; Lang, F.F. Cyclooxygenase-2 expression in human gliomas: Prognostic significance and molecular correlations. Cancer Res., 2001, 61(11), 4375-4381.
[PMID: 11389063]
[29]
Karim, A.; McCarthy, K.; Jawahar, A.; Smith, D.; Willis, B.; Nanda, A. Differential cyclooxygenase-2 enzyme expression in radiosensitive versus radioresistant glioblastoma multiforme cell lines. Anticancer Res., 2005, 25(1B), 675-679.
[PMID: 15816645]
[30]
Bijnsdorp, I.V.; van den Berg, J.; Kuipers, G.K.; Wedekind, L.E.; Slotman, B.J.; van Rijn, J.; Lafleur, M.V.M.; Sminia, P. Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells. J. Neurooncol., 2007, 85(1), 25-31.
[http://dx.doi.org/10.1007/s11060-007-9385-4] [PMID: 17447009]
[31]
Kang, K.B.; Wang, T.T.; Woon, C.T.; Cheah, E.S.; Moore, X.L.; Zhu, C.; Wong, M.C. Enhancement of glioblastoma radioresponse by a selective COX-2 inhibitor celecoxib: inhibition of tumor angiogen-esis with extensive tumor necrosis. Int. J. Radiat. Oncol. Biol. Phys., 2007, 67(3), 888-896.
[http://dx.doi.org/10.1016/j.ijrobp.2006.09.055] [PMID: 17293239]
[32]
Höcherl, K.; Schmidt, C.; Bucher, M. COX-2 inhibition attenuates endotoxin-induced downregula-tion of organic anion transporters in the rat renal cortex. Kidney Int., 2009, 75(4), 373-380.
[http://dx.doi.org/10.1038/ki.2008.557] [PMID: 18946499]
[33]
Asanuma, M.; Miyazaki, I. Nonsteroidal anti-inflammatory drugs in experimental parkinsonian models and Parkinson’s disease. Curr. Pharm. Des., 2008, 14(14), 1428-1434.
[http://dx.doi.org/10.2174/138161208784480153] [PMID: 18537665]
[34]
Sondhi, S.M.; Singh, N.; Kumar, A.; Lozach, O.; Meijer, L. Synthesis, anti-inflammatory, analgesic and kinase (CDK-1, CDK-5 and GSK-3) inhibition activity evaluation of benzimidazole/benzoxazole derivatives and some Schiff’s bases. Bioorg. Med. Chem., 2006, 14(11), 3758-3765.
[http://dx.doi.org/10.1016/j.bmc.2006.01.054] [PMID: 16480879]
[35]
Angajala, G.; Subashini, R. Synthesis, molecular modeling, and pharmacological evaluation of new 2-substituted benzoxazole derivatives as potent anti-inflammatory agents. J. Struct. Chem., 2020, 31(1), 263-273.
[http://dx.doi.org/10.1007/s11224-019-01374-1]
[36]
Aggarwal, N.; Kaur, A.; Anand, K.; Kumar, H.; Wakode, S. Biologically active Benzoxazole: A com-prehensive review. Int. J. Pharm. Sci. Res., 2017, 2(2), 1-15.
[37]
Aiello, S.; Wells, G.; Stone, E.L.; Kadri, H.; Bazzi, R.; Bell, D.R.; Stevens, M.F.; Matthews, C.S.; Bradshaw, T.D.; Westwell, A.D. Synthesis and biological properties of benzothiazole, benzoxazole, and chromen-4-one analogues of the potent antitumor agent 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (PMX 610, NSC 721648). J. Med. Chem., 2008, 51(16), 5135-5139.
[http://dx.doi.org/10.1021/jm800418z] [PMID: 18666770]
[38]
Dadmal, T.; Appalanaidu, K.; Kumbhare, R.M.; Mondal, T.; Ramaiah, M.J.; Bhadra, M.P. Synthesis and biological evaluation of triazole and isoxazole-tagged benzothiazole/benzoxazole derivatives as potent cytotoxic agents. NJC, 2018, 42(19), 15546-15551.
[http://dx.doi.org/10.1039/C8NJ01249K]
[39]
Sato, Y.; Yamada, M.; Yoshida, S.; Soneda, T.; Ishikawa, M.; Nizato, T.; Suzuki, K.; Konno, F. Ben-zoxazole derivatives as novel 5-HT3 receptor partial agonists in the gut. J. Med. Chem., 1998, 41(16), 3015-3021.
[http://dx.doi.org/10.1021/jm9801004] [PMID: 9685241]
[40]
Benazzouz, A.; Boraud, T.; Dubédat, P.; Boireau, A.; Stutzmann, J.M.; Gross, C. Riluzole prevents MPTP-induced parkinsonism in the rhesus monkey: A pilot study. Eur. J. Pharmacol., 1995, 284(3), 299-307.
[http://dx.doi.org/10.1016/0014-2999(95)00362-O] [PMID: 8666012]
[41]
Ryu, C-K.; Lee, R-Y.; Kim, N.Y.; Kim, Y.H.; Song, A.L. Synthesis and antifungal activity of ben-zo[d]oxazole-4,7-diones. Bioorg. Med. Chem. Lett., 2009, 19(20), 5924-5926.
[http://dx.doi.org/10.1016/j.bmcl.2009.08.062] [PMID: 19733068]
[42]
Kaplancikli, Z.A.; Turan-Zitouni, G.; Revial, G.; Guven, K. Synthesis and study of antibacterial and antifungal activities of novel 2-[[(benzoxazole/benzimidazole-2-yl)sulfanyl] acetylamino]thiazoles. Arch. Pharm. Res., 2004, 27(11), 1081-1085.
[http://dx.doi.org/10.1007/BF02975108] [PMID: 15595406]
[43]
Gadhe, D.; Chilumula, N.R.; Gudipati, R.; Ampati, S.; Manda, S. Synthesis of some novel methyl 2 (2 (arylideneamino) oxazol4 ylamino) benzoxazole 5carboxylate derivatives as antimicrobial agents. Int. J. Chem., 2010, 1(1), 1-6.
[44]
Elnima, E.I.; Zubair, M.U.; Al-Badr, A.A. Antibacterial and antifungal activities of benzimidazole and benzoxazole derivatives. Antimicrob. Agents Chemother., 1981, 19(1), 29-32.
[http://dx.doi.org/10.1128/AAC.19.1.29] [PMID: 7247359]
[45]
Katsura, Y.; Inoue, Y.; Nishino, S.; Tomoi, M.; Itoh, H.; Takasugi, H. Studies on antiulcer drugs. III. Synthesis and antiulcer activities of imidazo[1,2-a]pyridinylethylbenzoxazoles and related com-pounds. A novel class of histamine H2-receptor antagonists. Chem. Pharm. Bull. (Tokyo), 1992, 40(6), 1424-1438.
[http://dx.doi.org/10.1248/cpb.40.1424] [PMID: 1356641]
[46]
Sun, L-Q.; Chen, J.; Bruce, M.; Deskus, J.A.; Epperson, J.R.; Takaki, K.; Johnson, G.; Iben, L.; Mahle, C.D.; Ryan, E.; Xu, C. Synthesis and structure-activity relationship of novel benzoxazole de-rivatives as melatonin receptor agonists. Bioorg. Med. Chem. Lett., 2004, 14(14), 3799-3802.
[http://dx.doi.org/10.1016/j.bmcl.2004.04.082] [PMID: 15203165]
[47]
Davidson, J.P.; Corey, E.J. First enantiospecific total synthesis of the antitubercular marine natural product pseudopteroxazole. Revision of assigned stereochemistry. J. Am. Chem. Soc., 2003, 125(44), 13486-13489.
[http://dx.doi.org/10.1021/ja0378916] [PMID: 14583045]
[48]
Sessions, E.H.; Yin, Y.; Bannister, T.D.; Weiser, A.; Griffin, E.; Pocas, J.; Cameron, M.D.; Ruiz, C.; Lin, L.; Schürer, S.C.; Schröter, T.; LoGrasso, P.; Feng, Y. Benzimidazole- and benzoxazole-based inhibitors of Rho kinase. Bioorg. Med. Chem. Lett., 2008, 18(24), 6390-6393.
[http://dx.doi.org/10.1016/j.bmcl.2008.10.095] [PMID: 18996009]
[49]
Kakkar, S.; Tahlan, S.; Lim, S.M.; Ramasamy, K.; Mani, V.; Shah, S.A.A.; Narasimhan, B. Benzoxa-zole derivatives: Design, synthesis and biological evaluation. Chem. Cent. J., 2018, 12(1), 1-16.
[PMID: 29318401]
[50]
Perry, B.; Beezer, A.; Miles, R.; Smith, B.; Miller, J. Evaluation of microcalorimetry as a drug bioac-tivity screening procedure: Application to a series of novel Schiff base compounds. Microbios, 1986, 45(184-185), 181-191.
[51]
Patel, P.; Thaker, B.; Zele, S. Preparation and characterization of some lanthanide complexes involv-ing a heterocyclic β–diketone. Indian J. Chem., Sect. A: Inorg., Bio-inorg., Phys. Theor. Anal. Chem., 1999, 38(6), 563-567.
[52]
Imran, M.; Shah, F.A.; Nadeem, H.; Zeb, A.; Faheem, M.; Naz, S.; Bukhari, A.; Ali, T.; Li, S. Synthe-sis and biological evaluation of benzimidazole derivatives as potential neuroprotective agents in an ethanol-induced rodent model. ACS Chem. Neurosci., 2021, 12(3), 489-505.
[http://dx.doi.org/10.1021/acschemneuro.0c00659] [PMID: 33430586]
[53]
Xavier, A.; Srividhya, N. Synthesis and study of Schiff base ligands. IOSR-JAC., 2014, 7(11), 6-15.
[http://dx.doi.org/10.9790/5736-071110615]
[54]
Ashraf, Z.; Imran, M.; Amin, S. Synthesis, characterization and in vitro hydrolysis studies of ester and amide prodrugs of dexibuprofen. Med. Chem. Res., 2012, 21(11), 3361-3368.
[http://dx.doi.org/10.1007/s00044-011-9866-z]
[55]
Sun, H.; Tawa, G.; Wallqvist, A. Classification of scaffold-hopping approaches. Drug Discov. Today, 2012, 17(7-8), 310-324.
[http://dx.doi.org/10.1016/j.drudis.2011.10.024] [PMID: 22056715]
[56]
Seth, K.; Garg, S.K.; Kumar, R.; Purohit, P.; Meena, V.S.; Goyal, R.; Banerjee, U.C.; Chakraborti, A.K. 2-(2-Arylphenyl) benzoxazole as a novel anti-inflammatory scaffold: synthesis and biological evaluation. ACS Med. Chem. Lett., 2014, 5(5), 512-516.
[http://dx.doi.org/10.1021/ml400500e] [PMID: 24900871]
[57]
So, Y-H.; Heeschen, J.P.; Murlick, C.L. A mechanistic study of polybenzoxazole formation with model compounds. Macromolecules, 1995, 28(21), 7289-7290.
[http://dx.doi.org/10.1021/ma00125a038]
[58]
Apweiler, R.; Bairoch, A.; Wu, C.H.; Barker, W.C.; Boeckmann, B.; Ferro, S.; Gasteiger, E.; Huang, H.; Lopez, R.; Magrane, M.; Martin, M.J.; Natale, D.A.; O’Donovan, C.; Redaschi, N.; Yeh, L.S. UniProt: The universal protein knowledgebase. Nucleic Acids Res., 2004, 32(Database issue)(Suppl. 1), D115-D119.
[http://dx.doi.org/10.1093/nar/gkh131] [PMID: 14681372]
[59]
Berman, H.; Henrick, K.; Nakamura, H.; Markley, J.L. The worldwide Protein Data Bank (wwPDB): Ensuring a single, uniform archive of PDB data. Nucleic Acids Res., 2007, 35(Suppl. 1), D301-D303.
[http://dx.doi.org/10.1093/nar/gkl971] [PMID: 17142228]
[60]
Volkamer, A.; Kuhn, D.; Grombacher, T.; Rippmann, F.; Rarey, M. Combining global and local measures for structure-based druggability predictions. J. Chem. Inf. Model., 2012, 52(2), 360-372.
[http://dx.doi.org/10.1021/ci200454v] [PMID: 22148551]
[61]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. Au-toDock4 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]
[62]
Volkamer, A.; Kuhn, D.; Rippmann, F.; Rarey, M. DoGSiteScorer: A web server for automatic bind-ing site prediction, analysis and druggability assessment. J. Bioinform., 2012, 28(15), 2074-2075.
[http://dx.doi.org/10.1093/bioinformatics/bts310] [PMID: 22628523]
[63]
Willard, L.; Ranjan, A.; Zhang, H.; Monzavi, H.; Boyko, R.F.; Sykes, B.D.; Wishart, D.S. VADAR: A web server for quantitative evaluation of protein structure quality. Nucleic Acids Res., 2003, 31(13), 3316-3319.
[http://dx.doi.org/10.1093/nar/gkg565] [PMID: 12824316]
[64]
Ibrahim, S.R.M.; Mohamed, G.A.; Khayat, M.T.A.; Ahmed, S. Abo-Haded, H.; Garcixanthone, D. A new xanthone, and other xanthone derivatives from garcinia mangostana pericarps: Their α-amylase inhibitory potential and molecular docking studies. Stärke, 2019, 71(7-8), 1800354.
[http://dx.doi.org/10.1002/star.201800354]
[65]
Kankala, S.; Kankala, R.K.; Gundepaka, P.; Thota, N.; Nerella, S.; Gangula, M.R.; Guguloth, H.; Kagga, M.; Vadde, R.; Vasam, C.S. Regioselective synthesis of isoxazole-mercaptobenzimidazole hy-brids and their in vivo analgesic and anti-inflammatory activity studies. Bioorg. Med. Chem. Lett., 2013, 23(5), 1306-1309.
[http://dx.doi.org/10.1016/j.bmcl.2012.12.101] [PMID: 23357631]
[66]
Khan, M.T.; Nadeem, H.; Khan, A-U.; Abbas, M.; Arif, M.; Malik, N.S.; Malik, Z.; Javed, I. Amino acid conjugates of 2-mercaptobenzimidazole provide better anti-inflammatory pharmacology and im-proved toxicity profile. Drug Dev. Res., 2020, 81(8), 1057-1072.
[http://dx.doi.org/10.1002/ddr.21728]
[67]
Farghaly, A.A.; Bekhit, A.A.Y.; Park, J.Y. Design and synthesis of some oxadiazolyl, thiadiazolyl, thiazolidinyl, and thiazolyl derivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents. Arch. Pharm. (Weinheim), 2000, 333(2-3), 53-57.
[http://dx.doi.org/10.1002/(SICI)1521-4184(200002)333:2/3<53:AID-ARDP53>3.0.CO;2-E] [PMID: 10783518]
[68]
Noor, A.; Qazi, N.G.; Nadeem, H.; Khan, A-U.; Paracha, R.Z.; Ali, F.; Saeed, A. Synthesis, charac-terization, anti-ulcer action and molecular docking evaluation of novel benzimidazole-pyrazole hy-brids. Chem. Cent. J., 2017, 11(1), 85.
[http://dx.doi.org/10.1186/s13065-017-0314-0] [PMID: 29086868]
[69]
Griswold, D.E.; Adams, J.L. Constitutive cyclooxygenase (COX-1) and inducible cyclooxygenase (COX-2): Rationale for selective inhibition and progress to date. Med. Res. Rev., 1996, 16(2), 181-206.
[http://dx.doi.org/10.1002/(SICI)1098-1128(199603)16:2<181:AID-MED3>3.0.CO;2-X] [PMID: 8656779]
[70]
Peskar, B.M. Role of cyclooxygenase isoforms in gastric mucosal defence. J. Physiol. Paris, 2001, 95(1-6), 3-9.
[http://dx.doi.org/10.1016/S0928-4257(01)00003-1] [PMID: 11595412]
[71]
Konturek, P.C.; Kania, J.; Burnat, G.; Hahn, E.G.; Konturek, S.J. Prostaglandins as mediators of COX-2 derived carcinogenesis in gastrointestinal tract. J. Physiol. Pharmacol., 2005, 56(Suppl. 5), 57-73.
[PMID: 16247189]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version396msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[08:21:22] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[08:21:22] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[08:21:22] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[08:21:22] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (145ms)time
  • Application (252ms)time
  • 1 x Application (63.45%)
    252ms
    1 x Booting (36.54%)
    145ms
    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 duplicated147ms
    • 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 ('59354538','',1,1740471682,1740471682) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740471682
      1.38msalphaeurekaselec_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 ('59354538','/article/119529',1,1740471682,1740471682)
      250μsalphaeurekaselec_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 >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) 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 >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) 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 >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) 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 >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) 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 >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) 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 >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 59354538 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59354538) limit 1
      18.05msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 59354538
      • 1: 59354538
      • 2: 59354538
      • 3: 59354538
      • 4: 59354538
      • 5: 59354538
      • 6: 59354538
      • 7: 59354538
      • 8: 59354538
      • 9: 59354538
      • 10: 59354538
      • 11: 59354538
      • 12: 59354538
      • 13: 59354538
      • 14: 59354538
      • 15: 59354538
      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=119529
      1.09msalphaeurekaselec_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` = 50 limit 1
      22.57msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 50
      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=50) and sj.journal_id!=50 group by `j`.`nid`) as `aggregate_table`
      1.35msalphaeurekaselec_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
      1.05msalphaeurekaselec_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`
      2.22msalphaeurekaselec_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
      1.35msalphaeurekaselec_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` = '119529'
      860μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 119529
      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` = '119529'
      3.98msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 119529
      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` = '119529' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.42msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 119529
      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
      350μsalphaeurekaselec_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
      700μsalphaeurekaselec_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
      46.59msalphaeurekaselec_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
      8.41msalphaeurekaselec_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
      11.39msalphaeurekaselec_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` = 119529 limit 1
      330μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 119529
      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 = 119529 and content_type = 'article' order by status desc limit 1
      320μsalphaeurekaselec_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` = 199168 limit 1
      250μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 199168
      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
      280μsalphaeurekaselec_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
      380μsalphaeurekaselec_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 = '119529' 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) )
      570μsalphaeurekaselec_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 = '11572' 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) )
      450μsalphaeurekaselec_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 = '3136' 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) )
      410μsalphaeurekaselec_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 <= 59354538 and j.to_ip >=59354538 )) and ((j.from_date <= 1740471682 and j.to_date >= 1740471682 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3136) 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 <= 59354538 and j.to_ip >=59354538 )) and ((j.from_date <= 1740471682 and j.to_date >= 1740471682 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3136) 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 <= 59354538 and j.to_ip >=59354538 )) and ((j.from_date <= 1740471682 and j.to_date >= 1740471682 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3136)
      9.19msalphaeurekaselec_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 <= 59354538 and j.to_ip >=59354538 )) and ((j.from_date <= 1740471682 and j.to_date >= 1740471682 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11572) 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 <= 59354538 and j.to_ip >=59354538 )) and ((j.from_date <= 1740471682 and j.to_date >= 1740471682 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11572) 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 <= 59354538 and j.to_ip >=59354538 )) and ((j.from_date <= 1740471682 and j.to_date >= 1740471682 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11572)
      930μsalphaeurekaselec_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 <= 59354538 and j.to_ip >=59354538 )) and ((j.from_date <= 1740471682 and j.to_date >= 1740471682 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 119529) 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 <= 59354538 and j.to_ip >=59354538 )) and ((j.from_date <= 1740471682 and j.to_date >= 1740471682 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 119529) 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 <= 59354538 and j.to_ip >=59354538 )) and ((j.from_date <= 1740471682 and j.to_date >= 1740471682 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 119529)
      890μsalphaeurekaselec_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` < '791' and is_uploaded = 1 and issue_id = 11572 order by cast(first_page as SIGNED) desc limit 1
      720μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 791
      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` > '809' and is_uploaded = 1 and issue_id = 11572 order by cast(first_page as SIGNED) asc limit 1
      600μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 809
      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'
      350μsalphaeurekaselec_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
      340μsalphaeurekaselec_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` = 119529 limit 1
      3.93msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 119529
      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` <= 1740471682 and `b`.`banner_to_date` >= 1740471682 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.47msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 50
      • 3: 1740471682
      • 4: 1740471682
      • 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` <= 1740471682 and `b`.`banner_to_date` >= 1740471682 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.29msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 50
      • 3: 1740471682
      • 4: 1740471682
      • 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='df73e6ad04382d581399b4230e11d946'
      320μsalphaeurekaselec_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
        PRs5euR3AyvHSLCeAnRMJnO0uHdEjp1bkTUY611L
        uc_cart_id
        df73e6ad04382d581399b4230e11d946
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/article/119529" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/119529
        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:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6IjZDT21vbmFkYlc1VFFGMHV0ekoramc9PSIsInZhbHVlIjoiWFNOTEFFOXBUakZISjB4eTFackh2VGpQa2xpdUczZU85eDU3OEVKOEt2bz0iLCJtYWMiOiJkYWQyYzhlYmE5MDE0NDI3MDI3MjgxNzEyZTkxZTU1MDI2NzYxNGY1ZTYxMjBiNDZmZjdjMzRmMzQwNzE5ZjUzIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6IjZDT21vbmFkYlc1VFFGMHV0ekoramc9PSIsInZhbHVlIjoiWFNOTEFFOXBUakZISjB4eTFackh2VGpQa2xpdUczZU85eDU3OEVKOEt2bz0iLCJtYWMiOiJkYWQyYzhlYmE5MDE0" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "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" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        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 08:21:22 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InhLNmVwaWRQL0pBbUhNNWtneFJzblE9PSIsInZhbHVlIjoicythaEJKa01xbTVENzhPRWdLMTI0RHhMaFZ2b0Qwdk9ieGFjZjZoV1NxN1BRdGxsS0FJTmk4ZVAxWmRnTVFXYzhpaWNxdGt0cDUrZUR6MXJZclhBWkJ6OG1CMFM5eUNTbi9iWEE4SmZjTjJtMzF0WHQyWHJrWEdwQlBseFdDYmkiLCJtYWMiOiI5YjIwNmRhMGE5NDRiZjdiNTlkZjlkNzE2ODNlYmE5Y2Y4NGRjNjIyZWJiZDk4ZWY1YzM1Mzc0NWQwOTVlZTRmIiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 20:21:22 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6InhLNmVwaWRQL0pBbUhNNWtneFJzblE9PSIsInZhbHVlIjoicythaEJKa01xbTVENzhPRWdLMTI0RHhMaFZ2b0Qwdk9ieGFjZjZoV1NxN1BRdGxsS0FJTmk4ZVAxWmRnTVFXYzhpaWNxd" 1 => "alphaeurekaselectnet_session=eyJpdiI6InViNFJwSXU2K1Z5Zm5uc05LdXF6NHc9PSIsInZhbHVlIjoiOHY3V3o0TTFZSmJyVXBwTmtXMUk4TU5OeHRKNFEyRUhZRS9Jb1crWFBIUnFxb1JveEtxZUFlRHZ4YWlTTnZXUmNLU0RycWwrTEpaRmp6M1M2dytBZ3B2dEFEK3pKTVVQTE9IcG5PQkFZUFpmbjU4amJjOFgwbG55ajdhNGpVUWIiLCJtYWMiOiI2Y2U1OWJjOWM1NDM1N2E1NmFjZjExNzU5YTcyYThiYzMyOGZjZGI1OGMxNGZlMjkyMjgyNWU0OTdiM2RjNWY3IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6InViNFJwSXU2K1Z5Zm5uc05LdXF6NHc9PSIsInZhbHVlIjoiOHY3V3o0TTFZSmJyVXBwTmtXMUk4TU5OeHRKNFEyRUhZRS9Jb1crWFBIUnFxb1JveEtxZUFlRHZ" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InhLNmVwaWRQL0pBbUhNNWtneFJzblE9PSIsInZhbHVlIjoicythaEJKa01xbTVENzhPRWdLMTI0RHhMaFZ2b0Qwdk9ieGFjZjZoV1NxN1BRdGxsS0FJTmk4ZVAxWmRnTVFXYzhpaWNxdGt0cDUrZUR6MXJZclhBWkJ6OG1CMFM5eUNTbi9iWEE4SmZjTjJtMzF0WHQyWHJrWEdwQlBseFdDYmkiLCJtYWMiOiI5YjIwNmRhMGE5NDRiZjdiNTlkZjlkNzE2ODNlYmE5Y2Y4NGRjNjIyZWJiZDk4ZWY1YzM1Mzc0NWQwOTVlZTRmIiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 20:21:22 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6InhLNmVwaWRQL0pBbUhNNWtneFJzblE9PSIsInZhbHVlIjoicythaEJKa01xbTVENzhPRWdLMTI0RHhMaFZ2b0Qwdk9ieGFjZjZoV1NxN1BRdGxsS0FJTmk4ZVAxWmRnTVFXYzhpaWNxd" 1 => "alphaeurekaselectnet_session=eyJpdiI6InViNFJwSXU2K1Z5Zm5uc05LdXF6NHc9PSIsInZhbHVlIjoiOHY3V3o0TTFZSmJyVXBwTmtXMUk4TU5OeHRKNFEyRUhZRS9Jb1crWFBIUnFxb1JveEtxZUFlRHZ4YWlTTnZXUmNLU0RycWwrTEpaRmp6M1M2dytBZ3B2dEFEK3pKTVVQTE9IcG5PQkFZUFpmbjU4amJjOFgwbG55ajdhNGpVUWIiLCJtYWMiOiI2Y2U1OWJjOWM1NDM1N2E1NmFjZjExNzU5YTcyYThiYzMyOGZjZGI1OGMxNGZlMjkyMjgyNWU0OTdiM2RjNWY3IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6InViNFJwSXU2K1Z5Zm5uc05LdXF6NHc9PSIsInZhbHVlIjoiOHY3V3o0TTFZSmJyVXBwTmtXMUk4TU5OeHRKNFEyRUhZRS9Jb1crWFBIUnFxb1JveEtxZUFlRHZ" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "PRs5euR3AyvHSLCeAnRMJnO0uHdEjp1bkTUY611L" "uc_cart_id" => "df73e6ad04382d581399b4230e11d946" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/article/119529" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 08:21:22GET/article/119529414361