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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

Research Article

Synthesis and Cytotoxic Properties of New Substituted Glycosides-Indole Conjugates as Apoptosis Inducers in Cancer Cells

Author(s): Aladdin M. Srour, Mohamed N. El-Bayaa*, Mervat M. Omran, Marwa M. Sharaky and Wael A. El-Sayed*

Volume 21, Issue 10, 2021

Published on: 29 September, 2020

Page: [1323 - 1333] Pages: 11

DOI: 10.2174/1871520620666200929155246

Price: $65

Abstract

Background & Objective: Glycosyl heterocycles, being as nucleoside analogs with modified glycon and hybrid heterocycle motifs, are of considerable interest, and thus, the targeted compounds were synthesized via a convenient and efficient approach.

Methods: New indolyl-thiadiazolyl thioglycosides scaffolds were synthesized, starting with the reaction of indole-3-carbaldehyde with 2-aminothiadiazole-5-thiole followed by glycosylation and deprotection. Likewise, new molecular hybrids comprising indole, thiadiazole, triazole and glycosyl moieties were synthesized utilizing click chemistry strategy. The cytotoxic activities of the newly synthesized compounds were studied on colon carcinoma HCT116, breast carcinoma MCF-7, lung carcinoma A549 and hepatocellular carcinoma HepG2 cell lines using Sulphorhodamine-B (SRB) assay.

Results: The 1,3,4-thiadiazole thioglycoside and the 1,2,3-triazole N1-glycoside possessing xylose moiety, compounds 8 and 15 revealed the most potent bio-activity among the new chemical entities; therefore, they undertook for further analysis of apoptosis.

Conclusion: IC50s of Compound 8 were 38, 36, 33 and 158μg/ml, while they were 41, 44, 32 and 25μg/ml for compound 15 on HepG2, MCF7, HCT116 and A549 cell lines, respectively; furthermore, the total apoptosis rate (%) for control untreated cells were 9.63, 28.4, 25.4 (%), compounds 8 and 15 respectively, they produced a significant increase in total and early apoptosis rate (%) compared to control (P=0.0001). At the same time, no significant difference was detected in the late apoptosis rate (%), which means that both derivatives have the potential to be developed into potent anticancer agents.

Keywords: Indole-3-carbaldehyde, triazole, thiadiazole, glycosides, anticancer, apoptosis.

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[1]
Ferlay, J.S.I.; Ervik, M.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide; Lyon, France: International Agency for Research on Cancer, 2012.
[2]
Sommerwerk, S.; Heller, L.; Csuk, R. Synthesis and cytotoxic activity of pentacyclic triterpenoid sulfamates. Arch. Pharm. (Weinheim), 2015, 348(1), 46-54.
[http://dx.doi.org/10.1002/ardp.201400297] [PMID: 25581678]
[3]
Mok, N.Y.; Maxe, S.; Brenk, R. Locating sweet spots for screening hits and evaluating pan-assay interference filters from the performance analysis of two lead-like libraries. J. Chem. Inf. Model., 2013, 53(3), 534-544.
[http://dx.doi.org/10.1021/ci300382f] [PMID: 23451880]
[4]
Akhtar, J.; Khan, A.A.; Ali, Z.; Haider, R.; Shahar Yar, M. Structure-Activity Relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities. Eur. J. Med. Chem., 2017, 125, 143-189.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.023] [PMID: 27662031]
[5]
Kolb, H.C.; Sharpless, K.B. The growing impact of click chemistry on drug discovery. Drug Discov. Today, 2003, 8(24), 1128-1137.
[http://dx.doi.org/10.1016/S1359-6446(03)02933-7] [PMID: 14678739]
[6]
Bourne, Y.; Kolb, H.C.; Radić, Z.; Sharpless, K.B.; Taylor, P.; Marchot, P. Freeze-frame inhibitor captures acetylcholinesterase in a unique conformation. Proc. Natl. Acad. Sci. USA, 2004, 101(6), 1449-1454.
[http://dx.doi.org/10.1073/pnas.0308206100] [PMID: 14757816]
[7]
El-Sayed, W.A.; Abdel-Rahman, A.A-H. Copper-catalyzed synthesis and antimicrobial activity of disubstituted 1,2,3-triazoles starting from 1-propargyluracils and ethyl (4-azido- 1,2,3-trihydroxybutyl)furan-3-carboxylate. Monatsh. Chem., 2010, 65(1), 57.
[http://dx.doi.org/10.1515/znb-2010-0110]]
[8]
Broggi, J.; Joubert, N.; Aucagne, V.; Berteina-Raboin, S.; Diez-Gonzalez, S.; Nolan, S.; Topalis, D.; Deville-Bonne, D.; Balzarini, J.; Neyts, J.; Andrei, G.; Snoeck, R.; Agrofoglio, L.A. Alkyne-azide click chemistry mediated carbanucleosides synthesis. Nucleosides Nucleotides Nucleic Acids, 2007, 26(10-12), 1391-1394.
[http://dx.doi.org/10.1080/15257770701534139] [PMID: 18066789]
[9]
El-Sayed, W.A.; El-Essawy, F.A.; Ali, O.M.; Nasr, B.S.; Abdalla, M.M.; Abdel-Rahman, A.A.H. Synthesis and antiviral evaluation of new 2,5-disubstituted 1,3,4-oxadiazole derivatives and their acyclic nucleoside analogues. Monatsh. Chem., 2010, 141(9), 1021-1028.
[http://dx.doi.org/10.1007/s00706-010-0360-y]
[10]
Zhu, R.; Wang, M.; Xia, Y.; Qu, F.; Neyts, J.; Peng, L. Arylethynyltriazole acyclonucleosides inhibit hepatitis C virus replication. Bioorg. Med. Chem. Lett., 2008, 18(11), 3321-3327.
[http://dx.doi.org/10.1016/j.bmcl.2008.04.026] [PMID: 18445526]
[11]
Dutta, S.; Gupta, S.J.; Sen, A.K. Silver trifluoromethanesulfonate and metallic copper mediated syntheses of 1,2,3-triazole-O- and triazolyl glycoconjugates: Consecutive glycosylation and cyclization under one-pot condition. Tetrahedron Lett., 2016, 57(29), 3086-3090.
[http://dx.doi.org/10.1016/j.tetlet.2016.05.088]
[12]
Zhang, S-Y.; Fu, D-J.; Yue, X-X.; Liu, Y-C.; Song, J.; Sun, H-H.; Liu, H-M.; Zhang, Y-B. Design, synthesis and structure-activity relationships of novel chalcone-1, 2, 3-triazole-azole derivates as antiproliferative agents. Molecules, 2016, 21(5), 653.
[http://dx.doi.org/10.3390/molecules21050653] [PMID: 27213317]
[13]
Ruddarraju, R.R.; Murugulla, A.C.; Kotla, R.; Chandra Babu Tirumalasetty, M.; Wudayagiri, R.; Donthabakthuni, S.; Maroju, R.; Baburao, K.; Parasa, L.S. Design, synthesis, anticancer, antimicrobial activities and molecular docking studies of theophylline containing acetylenes and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives. Eur. J. Med. Chem., 2016, 123, 379-396.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.024] [PMID: 27487568]
[14]
Dondoni, A.; Marra, A. C-glycoside clustering on calix[4]arene, adamantane, and benzene scaffolds through 1,2,3-triazole linkers. J. Org. Chem., 2006, 71(20), 7546-7557.
[http://dx.doi.org/10.1021/jo0607156] [PMID: 16995658]
[15]
Megna, B.W.; Carney, P.R.; Nukaya, M.; Geiger, P.; Kennedy, G.D. Indole-3-carbinol induces tumor cell death: Function follows form. J. Surg. Res., 2016, 204(1), 47-54.
[http://dx.doi.org/10.1016/j.jss.2016.04.021] [PMID: 27451867]
[16]
Kumar, D.; Maruthi Kumar, N.; Tantak, M.P.; Ogura, M.; Kusaka, E.; Ito, T. Synthesis and identification of α-cyano bis(indolyl)chalcones as novel anticancer agents. Bioorg. Med. Chem. Lett., 2014, 24(22), 5170-5174.
[http://dx.doi.org/10.1016/j.bmcl.2014.09.085] [PMID: 25442306]
[17]
Yousif, M.N.; Hussein, H.A.; Yousif, N.M.; El-Manawaty, M.A.; El-Sayed, W.A. Synthesis and anticancer activity of novel 2- phenylindole linked imidazolothiazole, thiazolo-s-triazine and imidazolyl- sugar systems. J. Appl. Pharm. Sci., 2019, 9(01), 006-014..
[http://dx.doi.org/10.7324/JAPS.2019.90102]
[18]
Zhou, Y.; Duan, K.; Zhu, L.; Liu, Z.; Zhang, C.; Yang, L.; Li, M.; Zhang, H.; Yang, X. Synthesis and cytotoxic activity of novel hexahydropyrrolo[2,3-b]indole imidazolium salts. Bioorg. Med. Chem. Lett., 2016, 26(2), 460-465.
[http://dx.doi.org/10.1016/j.bmcl.2015.11.092] [PMID: 26684853]
[19]
Fortes, M.P.; da Silva, P.B.N.; da Silva, T.G.; Kaufman, T.S.; Militão, G.C.G.; Silveira, C.C. Synthesis and preliminary evaluation of 3-thiocyanato-1H-indoles as potential anticancer agents. Eur. J. Med. Chem., 2016, 118, 21-26.
[http://dx.doi.org/10.1016/j.ejmech.2016.04.039] [PMID: 27116711]
[20]
Gehrcke, M.; Giuliani, L.M.; Ferreira, L.M.; Barbieri, A.V.; Sari, M.H.M.; da Silveira, E.F.; Azambuja, J.H.; Nogueira, C.W.; Braganhol, E.; Cruz, L. Enhanced photostability, radical scavenging and antitumor activity of indole-3-carbinol-loaded rose hip oil nanocapsules. Mater. Sci. Eng. A Struct. Mater., 2017, 74, 279-286.
[http://dx.doi.org/10.1016/j.msec.2016.12.006] [PMID: 28254296]
[21]
El-Sayed, W.A.; El-Sofany, W.I.; Hussein, H.A.R.; Fathy, N.M.; Acids, N. Synthesis and anticancer activity of new [(Indolyl)pyrazolyl]-1,3,4-oxadiazole thioglycosides and acyclic nucleoside analogs. Nucleosides Nucleotides Nucleic Acids, 2017, 36(7), 474-495.
[http://dx.doi.org/10.1080/15257770.2017.1327665] [PMID: 28613111]
[22]
El-Sayed, W.A.; El-Kosy, S.M.; Ali, O.M.; Emselm, H.M.; Abdel-Rahman, A.A. Anticancer activity of new (tetrazol-5-yl)methylindole derivatives and their acyclic c-nucleoside analogs. Acta Pol. Pharm., 2012, 69(4), 669-677.
[PMID: 22876609]
[23]
Schuck, D.C.; Jordão, A.K.; Nakabashi, M.; Cunha, A.C.; Ferreira, V.F.; Garcia, C.R.S. Synthetic indole and melatonin derivatives exhibit antimalarial activity on the cell cycle of the human malaria parasite Plasmodium falciparum. Eur. J. Med. Chem., 2014, 78, 375-382.
[http://dx.doi.org/10.1016/j.ejmech.2014.03.055] [PMID: 24699367]
[24]
Rocha e Silva, L.F.; Montoia, A.; Amorim, R.C.N.; Melo, M.R.; Henrique, M.C.; Nunomura, S.M.; Costa, M.R.F.; Andrade Neto, V.F.; Costa, D.S.; Dantas, G.; Lavrado, J.; Moreira, R.; Paulo, A.; Pinto, A.C.; Tadei, W.P.; Zacardi, R.S.; Eberlin, M.N.; Pohlit, A.M. Comparative in vitro and in vivo antimalarial activity of the indole alkaloids ellipticine, olivacine, cryptolepine and a synthetic cryptolepine analog. Phytomedicine, 2012, 20(1), 71-76.
[http://dx.doi.org/10.1016/j.phymed.2012.09.008] [PMID: 23092722]
[25]
Khan, G.A.; War, J.A.; Naikoo, G.A.; Pandit, U.J.; Das, R. Porous CuO catalysed green synthesis of some novel 3-alkylated indoles as potent antitubercular agents. J. Saudi Chem. Soc., 2018, 22(1), 6-15.
[http://dx.doi.org/10.1016/j.jscs.2016.03.009]
[26]
El-Sayed, W.A.; Abdel Megeid, R.E.; Abbas, H-A.S. Synthesis and antimicrobial activity of new 1-[(tetrazol-5-yl)methyl] indole derivatives, their 1,2,4-triazole thioglycosides and acyclic analogs. Arch. Pharm. Res., 2011, 34(7), 1085-1096.
[http://dx.doi.org/10.1007/s12272-011-0706-y] [PMID: 21811915]
[27]
El-Sayed, W.; Abbas, A.; Mageid, R.; Magdziarz, T. Synthesis, antimicrobial activity and docking studies of new N-ethyl-3-indolyl heterocycles. Med. Chem. Res., 2015, 25(2), 339-355.
[http://dx.doi.org/10.1007/s00044-015-1488-4.]]
[28]
Singh, P.; Kaur, J.; Singh, G.; Bhatti, R. Triblock conjugates: Identification of a highly potent antiinflammatory agent. J. Med. Chem., 2015, 58(15), 5989-6001.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00952] [PMID: 26204057]
[29]
Mehndiratta, S.; Hsieh, Y-L.; Liu, Y-M.; Wang, A.W.; Lee, H-Y.; Liang, L-Y.; Kumar, S.; Teng, C-M.; Yang, C-R.; Liou, J-P. Indole-3-ethylsulfamoylphenylacrylamides: Potent histone deacetylase inhibitors with anti-inflammatory activity. Eur. J. Med. Chem., 2014, 85, 468-479.
[http://dx.doi.org/10.1016/j.ejmech.2014.08.020] [PMID: 25113875]
[30]
Abdel-Aal, M.T.; El-Sayed, W.A.; El-Kosy, S.M.; El-Ashry, S.H. Synthesis and antiviral evaluation of novel 5-(N-Aryl-aminomethyl-1,3,4-oxadiazol-2-yl)hydrazines and their sugars, 1,2,4-triazoles, tetrazoles and pyrazolyl derivatives. Arch. Pharm. (Weinheim), 2008, 341(5), 307-313.
[http://dx.doi.org/10.1002/ardp.200700154] [PMID: 18404774]
[31]
Matysiak, J. Biological and pharmacological activities of 1,3,4-thiadiazole based compounds. Mini Rev. Med. Chem., 2015, 15(9), 762-775.
[http://dx.doi.org/10.2174/1389557515666150519104057] [PMID: 25985954]
[32]
Haider, S.; Alam, M.S.; Hamid, H. 1,3,4-Thiadiazoles: A potent multi targeted pharmacological scaffold. Eur. J. Med. Chem., 2015, 92, 156-177.
[http://dx.doi.org/10.1016/j.ejmech.2014.12.035] [PMID: 25553540]
[33]
Aliabadi, A. 1,3,4-thiadiazole based anticancer agents. Anticancer. Agents Med. Chem., 2016, 16(10), 1301-1314.
[http://dx.doi.org/10.2174/1871520616666160628100936] [PMID: 27484056]
[34]
El-Sayed, W.A.; Metwally, M.A.; Nada, D.S.; Mohamed, A.A.; Abdel-Rahman, A.A-H. Synthesis and antimicrobial activity of new substituted 5-(pyridine-3-yl)-1,3,4-thiadiazoles and their sugar derivatives. J. Heterocycl. Chem., 2013, 50(2), 194-201.
[http://dx.doi.org/10.1002/jhet.901]
[35]
Zhang, K.; Wang, P.; Xuan, L-N.; Fu, X-Y.; Jing, F.; Li, S.; Liu, Y-M.; Chen, B-Q. Synthesis and antitumor activities of novel hybrid molecules containing 1,3,4-oxadiazole and 1,3,4-thiadiazole bearing Schiff base moiety. Bioorg. Med. Chem. Lett., 2014, 24(22), 5154-5156.
[http://dx.doi.org/10.1016/j.bmcl.2014.09.086] [PMID: 25442303]
[36]
Yadagiri, B.; Gurrala, S.; Bantu, R.; Nagarapu, L.; Polepalli, S.; Srujana, G.; Jain, N. Synthesis and evaluation of benzosuberone embedded with 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole moieties as new potential anti proliferative agents. Bioorg. Med. Chem. Lett., 2015, 25(10), 2220-2224.
[http://dx.doi.org/10.1016/j.bmcl.2015.03.032] [PMID: 25827522]
[37]
Li, Y-J.; Qin, Y-J.; Makawana, J.A.; Wang, Y-T.; Zhang, Y-Q.; Zhang, Y-L.; Yang, M-R.; Jiang, A-Q.; Zhu, H-L. Synthesis, biological evaluation and molecular modeling of 1,3,4-thiadiazol-2-amide derivatives as novel antitubulin agents. Bioorg. Med. Chem., 2014, 22(15), 4312-4322.
[http://dx.doi.org/10.1016/j.bmc.2014.05.017] [PMID: 24909678]
[38]
Guan, P.; Wang, L.; Hou, X.; Wan, Y.; Xu, W.; Tang, W.; Fang, H. Improved antiproliferative activity of 1,3,4-thiadiazole-containing Histone Deacetylase (HDAC) inhibitors by introduction of the heteroaromatic surface recognition motif. Bioorg. Med. Chem., 2014, 22(21), 5766-5775.
[http://dx.doi.org/10.1016/j.bmc.2014.09.039] [PMID: 25311567]
[39]
Hosseinzadeh, L.; Khorand, A.; Aliabadi, A. Discovery of 2-phenyl-N-(5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)acetamide derivatives as apoptosis inducers via the caspase pathway with potential anticancer activity. Arch. Pharm. (Weinheim), 2013, 346(11), 812-818.
[http://dx.doi.org/10.1002/ardp.201300180] [PMID: 24123162]
[40]
Hassan, A.; Ali, M.M.; Diaa, M.; Germoush, M.O.; Mohamed, A.M.; El-Sayed, W. Oxidative stress of some triazolopyrimidine derivatives and their nucleoside analogues on Mcf-7 and A549 cell lines. Egypt. J. Chem., 2020, 63(1), 247-253.
[http://dx.doi.org/10.21608/ejchem.2019.18248.2136]
[41]
Yousif, M.N.M.; Nassar, I.F.; Yousif, N.M.; Awad, H.M.; El-Sayed, W.A. Synthesis and anticancer activity of new substituted piperidinones linked to pyrimidine, thiazole, and triazole glycoside derivatives. Russ. J. Gen. Chem., 2019, 89(8), 1673-1682.
[http://dx.doi.org/10.1134/S1070363219080218]
[42]
Kassem, A.F.; Nassar, I.F.; Abdel-Aal, M.T.; Awad, H.M.; El-Sayed, W.A. Synthesis and anticancer activity of new ((furan-2-yl)-1,3,4-thiadiazolyl)-1,3,4-oxadiazole acyclic sugar derivatives. Chem. Pharm. Bull. (Tokyo), 2019, 67(8), 888-895.
[http://dx.doi.org/10.1248/cpb.c19-00280] [PMID: 31366838]
[43]
Khaw, P.T.; Sherwood, M.B.; MacKay, S.L.D.; Rossi, M.J.; Schultz, G. Five-minute treatments with fluorouracil, floxuridine, and mitomycin have long-term effects on human Tenon’s capsule fibroblasts. Arch. Ophthalmol., 1992, 110(8), 1150-1154.
[http://dx.doi.org/10.1001/archopht.1992.01080200130040] [PMID: 1386726]
[44]
Nassar, I.F. El kady, D.S.; Awad, H.M.; El-Sayed, W.A. Design, synthesis, and anticancer activity of new oxadiazolyl-linked and thiazolyl-linked benzimidazole arylidines, thioglycoside, and acyclic analogs. J. Heterocycl. Chem., 2019, 56(3), 1086-1100.
[http://dx.doi.org/10.1002/jhet.3496]
[45]
De Clercq, E. Antiviral drugs in current clinical use. J. Clin. Virol., 2004, 30(2), 115-133.
[http://dx.doi.org/10.1016/j.jcv.2004.02.009] [PMID: 15125867]
[46]
Tolan, H.E.M.; El-Sayed, W.A.; Tawfek, N.; Abdel-Megeid, F.M.E.; Kutkat, O.M. Synthesis and anti-H5N1 virus activity of triazole- and oxadiazole-pyrimidine hybrids and their nucleoside analogs. Nucleosides Nucleotides Nucleic Acids, 2020, 29(5), 649-670.
[http://dx.doi.org/10.1080/15257770.2019.1674331] [PMID: 31599202]
[47]
El-Sayed, W.A.; Fathi, N.M.; Gad, W.A.; El‐Ashry, E.S.H. Synthesis and antiviral evaluation of some 5‐N‐arylaminomethyl-2-glycosylsulphanyl‐1,3,4‐oxadiazoles and their analogs against hepatitis A and herpes simplex viruses. J. Carbohydr. Chem., 2008, 27(6), 357-372.
[http://dx.doi.org/10.1080/07328300802262778]
[48]
Jordheim, L.P.; Durantel, D.; Zoulim, F.; Dumontet, C. Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat. Rev. Drug Discov., 2013, 12(6), 447-464.
[http://dx.doi.org/10.1038/nrd4010] [PMID: 23722347]
[49]
Nassar, I.F.; El-Sayed, W.A.; Ragab, T.I.M.; Shalaby, A.S.G.; Mehany, A.B.M. Design, synthesis of new pyridine and pyrimidine sugar compounds as antagonists targeting the ERα via structure-based virtual screening. Mini Rev. Med. Chem., 2019, 19(5), 395-409.
[http://dx.doi.org/10.2174/1389557518666180820125210] [PMID: 30124151]
[50]
Rahman, A.A.H.A.; Nassar, I.F.; Shaban, A.K.F.; El-Kady, D.S.; Awad, H.M.; El Sayed, W.A. Synthesis, docking studies into CDK-2 and anticancer activity of new derivatives based pyrimidine scaffold and their derived glycosides. Mini Rev. Med. Chem., 2019, 19(13), 1093-1110.
[http://dx.doi.org/10.2174/1389557519666190312165717] [PMID: 30864522]
[51]
Kassem, A.F.; Abbas, E.M.H.; El-Kady, D.S.; Awad, H.M.; El-Sayed, W.A. Design, synthesis and anticancer activity of new thiazole-tetrazole or triazole hybrid glycosides targeting CDK-2 via structure-based virtual screening. Mini Rev. Med. Chem., 2019, 19(11), 933-948.
[http://dx.doi.org/10.2174/1389557519666181231121217] [PMID: 30599108]
[52]
Basiony, E.A.; Hassan, A.A.; Al-Amshany, Z.M.; Abd-Rabou, A.A.; Abdel-Rahman, A.A.; Hassan, N.A.; El-Sayed, W.A. Synthesis and cytotoxic activity of new thiazolopyrimidine sugar hydrazones and their derived acyclic nucleoside analogues. Molecules, 2020, 25(2), E399.
[http://dx.doi.org/10.3390/molecules25020399] [PMID: 31963649]
[53]
Saman, E.; Claeyssens, M.; Kersters-Hilderson, H.; De Bruyne, C.K. Letters: Azido compounds as potential affinity labels for glycosidases. Carbohydr. Res., 1973, 30(1), 207-210.
[http://dx.doi.org/10.1016/S0008-6215(00)82193-X] [PMID: 4755283]
[54]
Adesoye, O.G.; Mills, I.N.; Temelkoff, D.P.; Jackson, J.A.; Norris, P. Synthesis of a d-glucopyranosyl azide: Spectroscopic evidence for stereochemical inversion in the SN2 reaction. J. Chem. Educ., 2012, 89(7), 943-945.
[http://dx.doi.org/10.1021/ed200596p]
[55]
Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J.T.; Bokesch, H.; Kenney, S.; Boyd, M.R. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 1990, 82(13), 1107-1112.
[http://dx.doi.org/10.1093/jnci/82.13.1107] [PMID: 2359136]
[56]
Rochette, L.; Guenancia, C.; Gudjoncik, A.; Hachet, O.; Zeller, M.; Cottin, Y.; Vergely, C. Anthracyclines/trastuzumab: New aspects of cardiotoxicity and molecular mechanisms. Trends Pharmacol. Sci., 2015, 36(6), 326-348.
[http://dx.doi.org/10.1016/j.tips.2015.03.005] [PMID: 25895646]
[57]
Zhang, N.; Liu, D.; Wei, S.; Cao, S.; Feng, X.; Wang, K.; Ding, L.; Qiu, F. Phenylethanol glycosides from the seeds of Aesculus chinensis var. chekiangensis. BMC Chem., 2020, 14(1), 31.
[http://dx.doi.org/10.1186/s13065-020-00685-3] [PMID: 32337510]

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    • 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
    37 statements were executed, 4 of which were duplicates, 33 unique. Show only duplicated159ms
    • 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 ('873368187','',1,1740515030,1740515030) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740515030
      900μsalphaeurekaselec_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 ('873368187','/article/110333',1,1740515030,1740515030)
      140μsalphaeurekaselec_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 >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) 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 >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) 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 >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) 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 >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) 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 >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) 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 >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 873368187 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873368187) limit 1
      11.62msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 873368187
      • 1: 873368187
      • 2: 873368187
      • 3: 873368187
      • 4: 873368187
      • 5: 873368187
      • 6: 873368187
      • 7: 873368187
      • 8: 873368187
      • 9: 873368187
      • 10: 873368187
      • 11: 873368187
      • 12: 873368187
      • 13: 873368187
      • 14: 873368187
      • 15: 873368187
      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=110333
      630μsalphaeurekaselec_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
      720μsalphaeurekaselec_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`
      1.11msalphaeurekaselec_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
      890μsalphaeurekaselec_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`
      2.82msalphaeurekaselec_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
      2.37msalphaeurekaselec_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` = '110333'
      250μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 110333
      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` = '110333'
      2.41msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 110333
      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` = '110333' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      3.19msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 110333
      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
      300μsalphaeurekaselec_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
      630μsalphaeurekaselec_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
      38.66msalphaeurekaselec_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
      14.35msalphaeurekaselec_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
      10.98msalphaeurekaselec_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` = 110333 limit 1
      230μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 110333
      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 = 110333 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 a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 16 and cd.sub_disease_id = 457 and content_id!=110333 and cd.content_type = 'article' order by rand() limit 20
      46.17msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 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` = 186405 limit 1
      250μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 186405
      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
      220μsalphaeurekaselec_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
      290μsalphaeurekaselec_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 = '110333' 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) )
      350μsalphaeurekaselec_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 = '10503' 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) )
      270μsalphaeurekaselec_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 = '2919' 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) )
      270μsalphaeurekaselec_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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740515030 and j.to_date >= 1740515030 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2919) 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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740515030 and j.to_date >= 1740515030 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2919) 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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740515030 and j.to_date >= 1740515030 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2919)
      10.13msalphaeurekaselec_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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740515030 and j.to_date >= 1740515030 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10503) 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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740515030 and j.to_date >= 1740515030 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10503) 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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740515030 and j.to_date >= 1740515030 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10503)
      570μsalphaeurekaselec_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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740515030 and j.to_date >= 1740515030 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 110333) 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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740515030 and j.to_date >= 1740515030 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 110333) 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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740515030 and j.to_date >= 1740515030 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 110333)
      550μsalphaeurekaselec_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` < '1323' and is_uploaded = 1 and issue_id = 10503 order by cast(first_page as SIGNED) desc limit 1
      510μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 1323
      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` > '1333' and is_uploaded = 1 and issue_id = 10503 order by cast(first_page as SIGNED) asc limit 1
      400μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 1333
      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'
      210μsalphaeurekaselec_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
      290μsalphaeurekaselec_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` = 110333 limit 1
      2.74msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 110333
      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` <= 1740515030 and `b`.`banner_to_date` >= 1740515030 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.55msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1740515030
      • 4: 1740515030
      • 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` <= 1740515030 and `b`.`banner_to_date` >= 1740515030 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.26msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1740515030
      • 4: 1740515030
      • 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='cba159b3a0e3dac8636342a285a75d24'
      260μsalphaeurekaselec_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
        M3iBFHJo3zQvDoWcY994keh57Aa3IDMbLoSX5CFP
        uc_cart_id
        cba159b3a0e3dac8636342a285a75d24
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/110333" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/110333
        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
        []
        
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