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Current Organic Synthesis

Editor-in-Chief

ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Mini-Review Article

A Review on Onychine and its Analogs: Synthesis and Biological Activity

Author(s): Claudia R.B. Gomes, Marcus V.N. de Souza* and Victor Facchinetti

Volume 17, Issue 1, 2020

Page: [3 - 22] Pages: 20

DOI: 10.2174/1570179417666191218112842

Price: $65

Abstract

Background: Onychine is a 4-azafluorenone alkaloid isolated from the Annonaceae family, in low concentrations. Onychine and its analogs exhibit a wide range of pharmacological activities such as antifungal, antibacterial, anticancer, and antimalarial. Because of the high bioactivity of some 4-azafluorenone derivatives, several synthetic methods have been developed for their procurement.

Objective: Considering the importance of these alkaloids, we aim to present the main synthetic approaches to onychines and its derivatives and the biological activity of some 4-azafluorenones.

Methods: The most prominent methodologies for the synthesis of onychines were reviewed.

Results: In this work, we cover many synthetic approaches for the synthesis of onychine and 4-azafluorenone derivatives including intramolecular cyclizations, multicomponent reactions, microwave-assisted multicomponent reactions, Diels-alder reactions, among others. Moreover, we also review the biological activity of 4-azafluorenones.

Conclusion: 4-azafluorenones have risen as prominent structures in medicinal chemistry; however, most of the time, access to new derivatives involves toxic catalysts, harsh reaction conditions, and long-step procedures. Therefore, the development of new synthetic routes with more operational simplicity, simple purification procedure, good yields, and low environmental impact, is desirable.

Keywords: Onychine, 4-azafluorenone, synthetic methods, biological activity, alkaloid, medicinal chemistry.

Graphical Abstract

[1]
Bracher, F. A regioselective synthesis of azafluorenone alkaloids. Synlett, 1991, 95-96Available at .
[http://dx.doi.org/10.1055/s-1991-20639]
[2]
Dhara, S.; Ahmed, A.; Nandi, S.; Baitalik, S.; Ray, J.K. Synthesis of azafluorenone via oxidative intramolecular Heck cyclization. Tetrahedron Lett., 2013, 54, 63-65.Available at .
[http://dx.doi.org/10.1016/j.tetlet.2012.10.085]
[3]
Yoshida, N.C.; Siqueira, J.M.; Rodrigues, R.P.; Correia, R.P.; Garcez, W.S. An azafluorenone alkaloid and a megastigmane from Unonopsis lindmanii (Annonaceae). J. Braz. Chem. Soc., 2013, 24(4), 529-533.
[4]
Arita, M.; Yokoyama, S.; Asahara, H.; Nishiwaki, N. Facile Synthesis of onychines. Synthesis, 2019, 51, 2007-2013.Available at .
[http://dx.doi.org/10.1055/s-0037-1612058]
[5]
Achenbach’, H.; Schwinn, A. Synthesis of 2-Methoxyonychine Alkaloids - Structure revision of oxylopidine. Arch. Pharm. (Weinheim), 1994, 327, 755-762.Available at .
[http://dx.doi.org/10.1002/ardp.19943271202]
[6]
Taneichi, Y.; Shimada, K.; Korenaga, T. A short-step synthesis of onychine and the related 4-azafluorenones via hetero Diels-Alder reaction of 5-substituted isotellurazoles. Heterocycles, 2018, 96(3), 440-451.Available at .
[http://dx.doi.org/10.3987/COM-17-13865]
[7]
Koyama, J.; Okatani, T.; Tagahara, K.; Irie, H. Synthesis of alkaloids cleistopholine oxylopine isoursuline and ursuline. Heterocycles, 1989, 29(9), 1649-1654.Available at .
[http://dx.doi.org/10.3987/COM-89-5048]
[8]
Zhang, J.; el-Shabrawy, A-R.O.; el-Shanawany, M.A.; Schiff, P.L., Jr; Slatkin, D.J. New azafluorene alkaloids from oxandra xylopioides. J. Nat. Prod., 1987, 50(5), 800-806.Available at .
[http://dx.doi.org/10.1021/np50053a005]
[9]
Tadic, D.; Cassels, B.K.; Cavé, A. Spectral properties of ring-C-oxygenated 4-azafluorenes. The structures of natural onychine derivatives. Heterocycles, 1988, 27(2), 407-421.Available at .
[http://dx.doi.org/10.3987/COM-87-4376]
[10]
Sanchez, L.M.; Sathicq, A.G.; Romanelli, G.P.; González, L.M.; Villa, A.L. Activity of immobilized metallic phthalocyanines in the multicomponent synthesis of dihydropyridine derivatives and their subsequent aromatization. Mol. Catal, 2017, 435, 1-12.Available at .
[http://dx.doi.org/10.1016/j.mcat.2017.03.010]
[11]
Jana, A.; Mondal, J.; Borah, P.; Mondal, S.; Bhaumik, A.; Zhao, Y. Ruthenium bipyridyl tethered porous organosilica: A versatile, durable and reusable heterogeneous photocatalyst. Chem. Commun. (Camb.), 2015, 51(53), 10746-10749.Available at .
[http://dx.doi.org/10.1039/C5CC03067F] [PMID: 26051552]
[12]
Alves, T.; de Oliveira, A.B.; Snieckus, V. Short synthesis of azafluorenone alkaloids using transition metal-catalyzed. Tetrahedron Lett., 1988, 29(18), 2135-2136.Available at .
[http://dx.doi.org/10.1016/S0040-4039(00)86691-5]
[13]
Laha, J.K.; Patel, K.V. Saima; Pandey, S.; Solanke, G.; Vashisht, V. Scope of regioselective Suzuki reactions in the synthesis of arylpyridines and benzylpyridines and subsequent intramolecular cyclizations to azafluorenes and azafluorenones. New J. Chem., 2018, 42, 16069-16074.Available at .
[http://dx.doi.org/10.1039/C8NJ02734J]
[14]
Chun, Y.S.; Lee, J.H.; Kim, J.H.; Ko, Y.O.; Lee, S.G. Tandem one-pot synthesis of polysubstituted pyridines using the Blaise reaction intermediate and 1,3-enynes. Org. Lett., 2011, 13(24), 6390-6393.Available at .
[http://dx.doi.org/10.1021/ol202691b] [PMID: 22074496]
[15]
Pan, E.; Cao, S.; Brodie, P.J.; Callmander, M.W.; Randrianaivo, R.; Rakotonandrasana, S.; Rakotobe, E.; Rasamison, V.E.; TenDyke, K.; Shen, Y.; Suh, E.M.; Kingston, D.G.I. Isolation and synthesis of antiproliferative eupolauridine alkaloids of Ambavia gerrardii from the Madagascar Dry Forest. J. Nat. Prod., 2011, 74(5), 1169-1174.Available at .
[http://dx.doi.org/10.1021/np200093n] [PMID: 21504145]
[16]
Shimada, K.; Takata, Y.; Osaki, Y.; Moro-oka, A.; Kogawa, H.; Sakuraba, M.; Aoyagi, S.; Takikawa, Y.; Ogaw, S. Regioselective synthesis of polysubstituted pyridines via hetero-Diels-Alder reaction of isotellurazoles with acetylenic dienophiles. Tetrahedron Lett., 2009, 50, 6651-6653.Available at .
[http://dx.doi.org/10.1016/j.tetlet.2009.09.060]
[17]
Zhang, S.; Liao, L-Y.; Zhang, F.; Duan, X-F. Arylation, alkenylation, and alkylation of 2-halopyridine N-oxides with grignard reagents: A solution to the problem of C2/C6 regioselective functionalization of pyridine derivatives. J. Org. Chem., 2013, 78(6), 2720-2725.Available at .
[http://dx.doi.org/10.1021/jo302511s] [PMID: 23390982]
[18]
Tong, H.T.; Wong, H.N.C. Synthesis of eupolauridine and its benzo-annulated derivative. Synth. Commun., 1992, 22(12), 1773-1782.Available at .
[http://dx.doi.org/10.1080/00397919208020497]
[19]
Koyama, J.; Ogura, T.; Tagahara, K.; Miyashita, M. Irie, H. Synthesis of 5,6,7,8-tetrahydroquinolines by thermolysis of oxime-O-allyl ethers in the the presence of boron trifluoride etherate. Chem. Pharm. Bull. (Tokyo), 1993, 41(7), 1297-1298.Available at .
[http://dx.doi.org/10.1248/cpb.41.1297]
[20]
Irie, H.; Tanaka, S.; Zhang, Y.; Koyama, J.; Taga, T.; Machida, K. Synthesis of methoxy onychine and use of 1H and 13C-Nuclear Magnetic Resonance spectra for structure determination of geometrical isomers of indan-1-one oxime derivatives. Chem. Pharm. Bull. (Tokyo), 1988, 36, 3134-3137.Available at .
[http://dx.doi.org/10.1248/cpb.36.3134]
[21]
Tu, S.; Jiang, B.; Jia, R.; Zhang, J.; Zhang, Y. An efficient and expeditious microwave-assisted synthesis of 4-azafluorenones via a multi-component reaction. Tetrahedron Lett., 2007, 48(8), 1369-1374.Available at .
[http://dx.doi.org/10.1016/j.tetlet.2006.12.102]
[22]
Tu, S.; Jiang, B.; Jiang, H.; Zhang, Y.; Jia, R.; Zhang, J.; Shao, Q.; Li, C.; Zhou, D.; Cao, L. A novel three-component reaction for the synthesis of new 4-azafluorenone derivatives. Tetrahedron, 2007, 63, 5406-5414.Available at .
[http://dx.doi.org/10.1016/j.tet.2007.04.053]
[23]
Gul, H.I.; Tugrak, M.; Gul, M.; Sakagami, H.; Umemura, N.; Anil, B. Synthesis and cytotoxicities of new azafluorenones with apoptotic mechanism of action and cell cycle analysis. Anticancer. Agents Med. Chem., 2018, 18(12), 1770-1778.Available at .
[http://dx.doi.org/10.2174/1871520618666180525085445] [PMID: 29793413]
[24]
Addla, D. Bhima; Sridhar, B.; Devi, A.; Kantevari, S. Design, synthesis and antimicrobial evaluation of novel 1-benzyl 2-butyl-4-chloroimidazole embodied 4-azafluorenones via molecular hybridization approach. Bioorg. Med. Chem. Lett., 2012, 22(24), 7475-7480.Available at .
[http://dx.doi.org/10.1016/j.bmcl.2012.10.042] [PMID: 23147074]
[25]
Quiroga, J.; Cobo, D.; Insuasty, B.; Abonía, R. Regioselective three-component synthesis of novel indeno[1,2-b]- pyrazolo[4,3-e]pyridines-fused derivatives of 4-azafluorenone alkaloid. J. Heterocycl. Chem., 2008, 45, 155-159.Available at .
[http://dx.doi.org/10.1002/jhet.5570450116]
[26]
Kraus, G.A.; Kempema, A. Synthesis of azafluorenone antimicrobial agents. J. Nat. Prod., 2010, 73(11), 1967-1968.Available at .
[http://dx.doi.org/10.1021/np100536a] [PMID: 20964320]
[27]
Gibson, e.; Middleton, R.J. The intramolecular Heck reaction. Contemp. Org. Synth., 1996, 3(6), 447-471.Available at .
[http://dx.doi.org/10.1039/CO9960300447]
[28]
Marquise, N.; Harford, J.; Chevallier, F.; Roisnel, T.; Wheatley, A.E.H.; Gros, P.C.; Morgin, F. Efficient two-step access to azafluorenones and related compounds. Tetrahedron Lett., 2013, 54, 3154-3157.Available at .
[http://dx.doi.org/10.1016/j.tetlet.2013.04.020]
[29]
Marquise, N.; Floris, P.J.H.; Chevallier, F.; Roisnel, T.; Dorcet, V.; Gagez, A-L.; Sablée, S.; Picot, L.; Thiérye, V.; Wheatley, A.E.H.; Gros, P.C.; Mongin, F. Synthesis of azafluorenones and related compounds using deprotocuprationearoylation followed by intramolecular direct arylation. Tetrahedron, 2013, 69, 10123-10133.Available at .
[http://dx.doi.org/10.1016/j.tet.2013.09.030]
[30]
Marquise, N.; Dorcet, V.; Chevallier, F.; Mongin, F. Synthesis of substituted azafluorenones from dihalogeno diaryl ketones by palladium-catalyzed auto-tandem processes. Org. Biomol. Chem., 2014, 12(41), 8138-8141.Available at .
[http://dx.doi.org/10.1039/C4OB01629G] [PMID: 25233952]
[31]
Marquise, N.; Chevallier, F.; Nassar, E.; Frédérich, M.; Ledoux, A.; Halauko, Y.S.; Ivashkevich, O.A.; Matulis, V.E.; Roisnel, T.; Dorcet, V.; Morgin, F. Substituted azafluorenones: Access from dihalogeno diaryl ketones by palladium-catalyzed auto-tandem processes and evaluation of their antibacterial, antifungal, antimalarial and antiproleferative activities. Tetrahedron, 2016, 72, 825-836.Available at .
[http://dx.doi.org/10.1016/j.tet.2015.12.050]
[32]
Zheng, M.; Chen, P.; Wu, W.; Jiang, H. Palladium-catalyzed Heck-type reaction of oximes with allylic alcohols: Synthesis of pyridines and azafluorenones. Chem. Commun. (Camb.), 2016, 52(1), 84-87.Available at .
[http://dx.doi.org/10.1039/C5CC06958K] [PMID: 26496814]
[33]
Laha, J.K.; Jethava, K.P.; Patel, S.; Patel, K.V. Intramolecular acylation of unactivated pyridines or arenes via multiple C−H functionalizations: synthesis of all four azafluorenones and fluorenones. J. Org. Chem., 2017, 82(1), 76-85.Available at .
[http://dx.doi.org/10.1021/acs.joc.6b02065] [PMID: 27966934]
[34]
Laha, J.K.; Jethava, K.P.; Patel, S. Scope of successive C-H functionalizations of the methyl group in 3-Picolines: Intramolecular carbonylation of arenes to the metal-free synthesis of 4-Azafluorenones. Org. Lett., 2015, 17(23), 5890-5893.Available at .
[http://dx.doi.org/10.1021/acs.orglett.5b03071] [PMID: 26587583]
[35]
Mishra, K.; Pandey, A.K.; Singh, J.B.; Singh, R.M. Metal free TBHP-promoted intramolecular carbonylation of arenes via radical cross-dehydrogenative coupling: Synthesis of indenoquinolinones, 4-azafluorenones and fluorenones. Org. Biomol. Chem., 2016, 14(26), 6328-6336.Available at .
[http://dx.doi.org/10.1039/C6OB00998K] [PMID: 27270707]
[36]
Nishiyama, T.; Fujiwaki, T.; Hatae, N.; Uchiyama, E.; Takeuchi, N.; Minami, K.; Yokoyama, C.; Kinoshita, T.; Ishikura, M.; Hibino, S.; Choshi, T. Concise synthesis of azafluorenone and its application to indeno[1,2-c]isoquinolone. Heterocycles, 2018, 97(1), 383-394.Available at .
[http://dx.doi.org/10.3987/COM-18-S(T)26]
[37]
Hong, B-C.; Hallur, M.S. Liao. J.-H. Hetero Diels–Alder cycloaddition of indene for the formal synthesis of onychnine. Synth. Commun., 2006, 36(11), 521.Available at .
[http://dx.doi.org/10.1080/00397910600588520]
[38]
Nitta, M.; Ohnuma, M. On the Reaction of N-Vinyliminophosphoranes. Part 16.' A New Synthesis of 5H-indeno [1,2-b] pyridines and 5H-indeno [1,2-b] pyridin-5-ones J. Chem. Soc. Perkin Trans,, 1991, 1115-1118.
[39]
Clary, K.N.; Back, T.G. Synthesis of onychine and formal synthesis of eupolauridine via the vinylogous aza-Morita-Baylis-Hillman reaction. Synlett, 2010, 18, 2802-2804.
[40]
Tsuzuki, J.K.; Svidzinski, T.I.E.; Shinobu, C.S.; Silva, L.F.A.; Rodrigues-Filho, E.; Cortez, D.A.G.; Ferreira, I.C.P. Antifungal activity of the extracts and saponins from Sapindus saponaria L. An. Acad. Bras. Cienc., 2007, 79(4), 577-583.
[http://dx.doi.org/10.1590/S0001-37652007000400002] [PMID: 18066429]
[41]
Gupta, A.K.; Cooper, E.A. Update in antifungal therapy of dermatophytosis. Mycopathologia, 2008, 166(5-6), 353-367.Available at .
[http://dx.doi.org/10.1007/s11046-008-9109-0] [PMID: 18478357]
[42]
Li, W.R.; Shi, Q.S.; Dai, H.Q.; Liang, Q.; Xie, X.B.; Huang, X.M.; Zhao, G.Z.; Zhang, L.X. Antifungal activity, kinetics and molecular mechanism of action of garlic oil against Candida albicans. Sci. Rep., 2016, 6, 22805.Available at .
[http://dx.doi.org/10.1038/srep22805] [PMID: 26948845]
[43]
Lu, Y.; Su, C.; Liu, H. Candida albicans hyphal initiation and elongation. Trends Microbiol., 2014, 22(12), 707-714.Available at .
[http://dx.doi.org/10.1016/j.tim.2014.09.001] [PMID: 25262420]
[44]
Choi, H.; Lee, D.G. Antifungal activity and pore-forming mechanism of astacidin 1 against Candida albicans. Biochimie, 2014, 105, 58-63.Available at .
[http://dx.doi.org/10.1016/j.biochi.2014.06.014] [PMID: 24955933]
[45]
Ramage, G.; Vande Walle, K.; Wickes, B.L.; López-Ribot, J.L. Standardized method for in vitro antifungal susceptibility testing of Candida albicans biofilms. Antimicrob. Agents Chemother., 2001, 45(9), 2475-2479.Available at .
[http://dx.doi.org/10.1128/AAC.45.9.2475-2479.2001] [PMID: 11502517]
[46]
He, M.; Du, M.; Fan, M.; Bian, Z. In vitro activity of eugenol against Candida albicans biofilms. Mycopathologia, 2007, 163(3), 137-143.Available at .
[http://dx.doi.org/10.1007/s11046-007-0097-2] [PMID: 17356790]
[47]
Douglas, L.J. Candida biofilms and their role in infection. Trends Microbiol., 2003, 11(1), 30-36.Available at .
[http://dx.doi.org/10.1016/S0966-842X(02)00002-1] [PMID: 12526852]
[48]
Hufford, C.D.; Liu, S.; Clark, A.M.; Oguntimein, B.O. Anticandidal activity of eupolauridine and onychine, alkaloids from Cleistopholis patens. J. Nat. Prod., 1987, 50(5), 961-964.Available at .
[http://dx.doi.org/10.1021/np50053a037] [PMID: 3325614]
[49]
Koyama, J.; Morita, I.; Kobayashi, N.; Osakai, T.; Usuki, Y.; Taniguchi, M. Structure-activity relations of azafluorenone and azaanthraquinone as antimicrobial compounds. Bioorg. Med. Chem. Lett., 2005, 15(4), 1079-1082.Available at .
[http://dx.doi.org/10.1016/j.bmcl.2004.12.059] [PMID: 15686916]
[50]
Vellasco, W.T., Jr; Guedes, G.P.; Facchinetti, V.; Vasconcelos, T.R.A.; Vaz, M.G.F.; Cunico, W.; de Souza, M.V.; de Paula, G.R.; Fleming, M.E.C.K.; Gomes, C.R.B. Antibacterial activity of thioetherhydroxyethylsulfonamide derivatives. Med. Chem., 2014, 10(3), 271-276.Available at .
[http://dx.doi.org/10.2174/1573406410666140218103022] [PMID: 24533504]
[51]
Lee, D.K.; Hwang, J.U.; Baek, E.H.; Lee, K.O.; Kim, K.J.; Ha, N.J. New antimicrobial drug resistance and epidemiological typing patterns of Staphylococci from clinical isolates and raw meats. Arch. Pharm. Res., 2008, 31(8), 1016-1022.Available at .
[http://dx.doi.org/10.1007/s12272-001-1262-x] [PMID: 18787791]
[52]
Centers for Disease Control and Prevention Vital Signs: Containing Unusual Resistance., Available at . https://www.cdc.gov/vitalsigns/pdf/2018-04-vitalsigns.pdf
[53]
Appelbaum, P.C. 2012 and beyond: potential for the start of a second pre-antibiotic era? J. Antimicrob. Chemother., 2012, 67(9), 2062-2068.Available at .
[http://dx.doi.org/10.1093/jac/dks213] [PMID: 22687888]
[54]
Fair, R.J.; Tor, Y. Antibiotics and bacterial resistance in the 21st century. Perspect. Medicin. Chem., 2014, 6, 25-64.Available at .
[http://dx.doi.org/10.4137/PMC.S14459] [PMID: 25232278]
[55]
Center for Infectious Disease Reasearch and Policy, University of Minnesota Overuse and Overprescribing of Antibiotics., Available from: . http://www.cidrap.umn.edu/asp/overuse-overprescribing-of-antibiotics (Accessed on August 02, 2019)
[56]
de Souza, M.V.N.; Facchinetti, V.; Cardinot, D.; Gomes, C.R.B. Produtos aturais com atividade inibitória da Translocase I, uma promissora classe de compostos contra tuberculose. Bol. Latinoam. Caribe Plantas Med. Aromat., 2009, 9(1), 1-12.
[57]
Furin, J.; Cox, H.; Pai, M. Tuberculosis. Lancet, 2019, 393(10181), 1642-1656.Available at .
[http://dx.doi.org/10.1016/S0140-6736(19)30308-3] [PMID: 30904262]
[58]
Fogel, N. Tuberculosis: A disease without boundaries. Tuberculosis (Edinb.), 2015, 95(5), 527-531.Available at .
[http://dx.doi.org/10.1016/j.tube.2015.05.017] [PMID: 26198113]
[59]
Prachayasittikul, S.; Manam, P.; Chinworrungsee, M.; Isarankura-Na-Ayudhya, C.; Ruchirawat, S.; Prachayasittikul, V. Bioactive azafluorenone alkaloids from Polyalthia debilis (Pierre) Finet & Gagnep. Molecules, 2009, 14(11), 4414-4424.Available at .
[http://dx.doi.org/10.3390/molecules14114414] [PMID: 19924075]
[60]
Pumsalid, K.; Thaisuchat, H.; Loetchutinat, C.; Nuntasaen, N.; Meepowpan, P.; Pompimon, W. A new azafluorenone from the roots of Polyalthia cerasoides and its biological activity. Nat. Prod. Commun., 2010, 5(12), 1931-1934.Available at .
[http://dx.doi.org/10.1177/1934578X1000501219] [PMID: 21299123]
[61]
Merlo, L.M.F.; Pepper, J.W.; Reid, B.J.; Maley, C.C. Cancer as an evolutionary and ecological process. Nat. Rev. Cancer, 2006, 6(12), 924-935.Available at .
[http://dx.doi.org/10.1038/nrc2013] [PMID: 17109012]
[62]
Sarkar, S.; Horn, G.; Moulton, K.; Oza, A.; Byler, S.; Kokolus, S.; Longacre, M. Cancer development, progression, and therapy: An epigenetic overview. Int. J. Mol. Sci., 2013, 14(10), 21087-21113.
[http://dx.doi.org/10.3390/ijms141021087] [PMID: 24152442]
[63]
Papaccio, F.; Paino, F.; Regad, T.; Papaccio, G.; Desiderio, V.; Tirino, V. Concise review: Cancer cells, cancer stem cells, and mesenchymal stem cells: Influence in cancer development. Stem Cells Transl. Med., 2017, 6(12), 2115-2125.Available at .
[http://dx.doi.org/10.1002/sctm.17-0138] [PMID: 29072369]
[64]
World Health Organization Available at . https://www.who.int/en/news-room/fact-sheets/detail/cancer (accessed August 06, 2019)
[65]
Shih, Y.C.; Hurria, A. Preparing for an epidemic: Cancer care in an aging population. Am. Soc. Clin. Oncol. Educ. Book, 2014, 34, 133-137.Available at .
[http://dx.doi.org/10.14694/EdBook_AM.2014.34.133] [PMID: 24857069]
[66]
Magalhaes, L.G.; Ferreira, L.L.G.; Andricopulo, A.D. Recent advances and perspectives in cancer drug design. An. Acad. Bras. Cienc., 2018, 90(1)(Suppl. 2), 1233-1250.Available at .
[http://dx.doi.org/10.1590/0001-3765201820170823] [PMID: 29768576]
[67]
Rayan, A.; Raiyn, J.; Falah, M. Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity. PLoS One, 2017, 12(11),e0187925.Available at .
[http://dx.doi.org/10.1371/journal.pone.0187925.] [PMID: 29121120]
[68]
Lago, J.H.G.; Chaves, M.H.; Ayres, M.C.C.; Agripino, D.G.; Young, M.C.M. Evaluation of antifungal and DNA-damaging activities of alkaloids from branches of Porcelia macrocarpa. Planta Med., 2007, 73(3), 292-295.Available at .
[http://dx.doi.org/10.1055/s-2007-967108] [PMID: 17354171]
[69]
Tugrak, M.; Inci Gul, H.; Sakagami, H.; Gulcin, I.; Supuran, C.T. New azafluorenones with cytotoxic and carbonic anhydrase inhibitory properties: 2-Aryl-4-(4-hydroxyphenyl)-5H-indeno[1,2-b]pyridin-5-ones. Bioorg. Chem., 2018, 81, 433-439.Available at .
[http://dx.doi.org/10.1016/j.bioorg.2018.09.013] [PMID: 30223148]
[70]
Muluye, A.B.; Desta, A.G.; Abate, S.K.; Dano, G.T. Anti-malarial activity of the root extract of Euphorbia abyssinica (Euphorbiaceae) against Plasmodium berghei infection in mice. Malar. J., 2019, 18(1), 261.Available at .
[http://dx.doi.org/10.1186/s12936-019-2887-7] [PMID: 31362744]
[71]
World Health Organization. Available from: . https://www.who.int/news-room/fact-sheets/detail/malaria. (Accessed on August 08, 2019)
[72]
Aguiar, A.C.C.; Murce, E.; Cortopassi, W.A.; Pimentel, A.S.; Almeida, M.M.F.S.; Barros, D.C.S.; Guedes, J.S.; Meneghetti, M.R.; Krettli, A.U. Chloroquine analogs as antimalarial candidates with potent in vitro and in vivo activity. Int. J. Parasitol. Drugs Drug Resist., 2018, 8(3), 459-464.Available at .
[http://dx.doi.org/10.1016/j.ijpddr.2018.10.002] [PMID: 30396013]
[73]
Souza, M.C.; Padua, T.A.; Torres, N.D.; Costa, M.F.S.; Facchinetti, V.; Gomes, C.R.B.; Souza, M.V.; Henriques, Md. Study of the antimalarial properties of hydroxyethylamine derivatives using green fluorescent protein transformed Plasmodium berghei. Mem. Inst. Oswaldo Cruz, 2015, 110(4), 560-565.Available at .
[http://dx.doi.org/10.1590/0074-02760140466] [PMID: 26018449]
[74]
Das, S.; Saha, B.; Hati, A.K.; Roy, S. Evidence of artemisinin-resistant plasmodium falciparum malaria in eastern India. N. Engl. J. Med., 2018, 379(20), 1962-1964.Available at .
[http://dx.doi.org/10.1056/NEJMc1713777] [PMID: 30428283]
[75]
Suresh, N.; Haldar, K. Mechanisms of artemisinin resistance in Plasmodium falciparum malaria. Curr. Opin. Pharmacol., 2018, 42, 46-54.Available at .
[http://dx.doi.org/10.1016/j.coph.2018.06.003] [PMID: 30077118]
[76]
Mueller, D.; Davis, R.A.; Duffy, S.; Avery, V.M.; Camp, D.; Quinn, R.J. Antimalarial activity of azafluorenone alkaloids from the Australian tree Mitrephora diversifolia. J. Nat. Prod., 2009, 72(8), 1538-1540.Available at .
[http://dx.doi.org/10.1021/np900247f] [PMID: 19591451]

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Request history8.2.27PHP Version362msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[05:07:33] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[05:07:33] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[05:07:33] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (110ms)time
  • Application (252ms)time
  • 1 x Application (69.6%)
    252ms
    1 x Booting (30.4%)
    110ms
    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
    37 statements were executed, 4 of which were duplicates, 33 unique. Show only duplicated160ms
    • 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 ('59885649','',1,1740460053,1740460053) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740460053
      1.09msalphaeurekaselec_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 ('59885649','/article/103053',1,1740460053,1740460053)
      200μsalphaeurekaselec_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 >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) 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 >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) 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 >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) 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 >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) 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 >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) 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 >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 59885649 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59885649) limit 1
      11.54msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 59885649
      • 1: 59885649
      • 2: 59885649
      • 3: 59885649
      • 4: 59885649
      • 5: 59885649
      • 6: 59885649
      • 7: 59885649
      • 8: 59885649
      • 9: 59885649
      • 10: 59885649
      • 11: 59885649
      • 12: 59885649
      • 13: 59885649
      • 14: 59885649
      • 15: 59885649
      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=103053
      680μsalphaeurekaselec_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` = 34 limit 1
      810μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 34
      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=34) and sj.journal_id!=34 group by `j`.`nid`) as `aggregate_table`
      610μsalphaeurekaselec_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=34) and sj.journal_id!=34 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      710μsalphaeurekaselec_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=34) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.11msalphaeurekaselec_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=34) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.03msalphaeurekaselec_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` = '103053'
      1.48msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 103053
      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` = '103053'
      3.58msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 103053
      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` = '103053' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      1.23msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 103053
      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
      240μsalphaeurekaselec_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
      460μsalphaeurekaselec_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 = 34 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      31.77msalphaeurekaselec_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 = 34 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      9.54msalphaeurekaselec_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 = 34 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      5.61msalphaeurekaselec_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` = 103053 limit 1
      230μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 103053
      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 = 103053 and content_type = 'article' order by status desc limit 1
      910μsalphaeurekaselec_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 = 466 and content_id!=103053 and cd.content_type = 'article' order by rand() limit 20
      67.4msalphaeurekaselec_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` = 177595 limit 1
      250μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 177595
      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
      250μsalphaeurekaselec_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` = 'COS' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      310μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: COS
      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 = '103053' 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) )
      380μsalphaeurekaselec_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 = '9676' 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) )
      320μsalphaeurekaselec_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 = '2722' 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) )
      310μsalphaeurekaselec_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 <= 59885649 and j.to_ip >=59885649 )) and ((j.from_date <= 1740460053 and j.to_date >= 1740460053 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2722) 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 <= 59885649 and j.to_ip >=59885649 )) and ((j.from_date <= 1740460053 and j.to_date >= 1740460053 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2722) 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 <= 59885649 and j.to_ip >=59885649 )) and ((j.from_date <= 1740460053 and j.to_date >= 1740460053 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2722)
      9.97msalphaeurekaselec_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 <= 59885649 and j.to_ip >=59885649 )) and ((j.from_date <= 1740460053 and j.to_date >= 1740460053 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9676) 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 <= 59885649 and j.to_ip >=59885649 )) and ((j.from_date <= 1740460053 and j.to_date >= 1740460053 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9676) 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 <= 59885649 and j.to_ip >=59885649 )) and ((j.from_date <= 1740460053 and j.to_date >= 1740460053 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9676)
      590μsalphaeurekaselec_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 <= 59885649 and j.to_ip >=59885649 )) and ((j.from_date <= 1740460053 and j.to_date >= 1740460053 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 103053) 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 <= 59885649 and j.to_ip >=59885649 )) and ((j.from_date <= 1740460053 and j.to_date >= 1740460053 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 103053) 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 <= 59885649 and j.to_ip >=59885649 )) and ((j.from_date <= 1740460053 and j.to_date >= 1740460053 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 103053)
      600μsalphaeurekaselec_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` < '3' and is_uploaded = 1 and issue_id = 9676 order by cast(first_page as SIGNED) desc limit 1
      500μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 3
      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` > '22' and is_uploaded = 1 and issue_id = 9676 order by cast(first_page as SIGNED) asc limit 1
      440μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 22
      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'
      180μsalphaeurekaselec_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
      200μsalphaeurekaselec_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` = 103053 limit 1
      2.61msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 103053
      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` = 34 and `b`.`banner_from_date` <= 1740460053 and `b`.`banner_to_date` >= 1740460053 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.58msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 34
      • 3: 1740460053
      • 4: 1740460053
      • 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` = 34 and `b`.`banner_from_date` <= 1740460053 and `b`.`banner_to_date` >= 1740460053 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.14msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 34
      • 3: 1740460053
      • 4: 1740460053
      • 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='a5639a90e712d32a10a3c3b83e988aca'
      230μsalphaeurekaselec_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
        RHU9C3LzXxpslAYLhAW6Vid6LUWgdYzduqPdAV20
        uc_cart_id
        a5639a90e712d32a10a3c3b83e988aca
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/103053" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/103053
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
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