Vanillin-Related N-Acylhydrazones: Synthesis, Antischistosomal Properties and Target Fishing Studies

Author(s): Daniela G.G. Rando , Marcela O.L. da Costa , Thais F.A. Pavani , Thiago Oliveira , Paloma F. dos Santos , Carina R. Amorim , Pedro L.S. Pinto , Mariana G. de Brito , Marcos P.N. Silva , Daniel B. Roquini , Josué de Moraes* .

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 14 , 2019

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Graphical Abstract:


Background: Schistosomiasis is a neglected disease, which affects millions of people in developing countries. Its treatment relies on a single therapeutic alternative, the praziquantel. This situation may lead to drug resistance which, in turn, made urgent the need for new antischistosomal agents. Nacylhydrazones are usually explored as good antimicrobial agents, but the vanillin-related N-acylhydrazones have never been tested by their antiparasitic potential.

Objective: Herein, we report the synthesis of seven analogues, three of them unpublished, their biological investigation against Schistosoma mansoni and Target Fishing studies.

Methods: The compounds were synthesized following classical synthetical approaches. The anthelmintic potential was assessed as well as their cytotoxicity profile. Confocal laser scanning microscopy and target fishing study were performed to better understand the observed antischistosomal activity.

Results: Compound GPQF-407 exhibited good antischistosomal activity (47.91 µM) with suitable selectivity index (4.14). Confocal laser scanning microscopy revealed that it triggered severe tegumental destruction and tubercle disintegration. Target fishing studies pointed out some probable targets, such as the serine-threonine kinases, dihydroorotate dehydrogenases and carbonic anhydrase II.

Conclusion: The GPQF-407 was revealed to be a promising antischistosomal agent which, besides presenting the N-acylhydrazone privileged scaffold, also could be easily synthesized on large scales from commercially available materials.

Keywords: Schistosoma mansoni, Schistosomiasis, N-acylhydrazones, Vanillin derivatives, Target Fishing, Antischistosomal compounds.

Beckmann, S.; Leutner, S.; Gouignard, N.; Dissous, C.; Grevelding, C.G. Protein kinases as potential targets for novel anti-schistosomal strategies. Curr. Pharm. Des., 2012, 18(24), 3579-3594.
[] [PMID: 22607148]
Mafud, A.C.; Ferreira, L.G.; Mascarenhas, Y.P.; Andricopulo, A.D.; de Moraes, J. Discovery of novel antischistosomal agents by molecular modeling approaches. Trends Parasitol., 2016, 32(11), 874-886.
[] [PMID: 27593339]
Grimes, J.E.; Croll, D.; Harrison, W.E.; Utzinger, J.; Freeman, M.C.; Templeton, M.R. The roles of water, sanitation and hygiene in reducing schistosomiasis: A review. Parasit. Vectors, 2015, 8(1), 156.
[] [PMID: 25884172]
Kassebaum, N.J.; Arora, M.; Barber, R.M.; Brown, J.; Carter, A.; Casey, D.C.; Charlson, F.J.; Coates, M.M.; Coggeshall, M.; Cornaby, L. Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: A systematic analysis for the global burden of disease study 2015. Lancet, 2016, 388(10053), 1603-1658.
[] [PMID: 27733283]
Goldberg, E.M.; Pigott, D.; Shirude, S.; Stanaway, J.; Hay, S.I.; Vos, T. Underestimation of the global burden of schistosomiasis-Authors’ reply. Lancet, 2018, 391(10118), 308.
[] [PMID: 29413043]
Lago, E.M.; Xavier, R.P.; Teixeira, T.R.; Silva, L.M.; da Silva Filho, A.A.; de Moraes, J. Antischistosomal agents: state of art and perspectives. Future Med. Chem., 2018, 10(1), 89-120.
[] [PMID: 29235368]
Cioli, D.; Pica-Mattoccia, L.; Basso, A.; Guidi, A. Schistosomiasis control: Praziquantel forever? Mol. Biochem. Parasitol., 2014, 195(1), 23-29.
[] [PMID: 24955523]
Schistosomiasis, [Feb 14, 2018]. (Available at:,
de Moraes, J. Natural products with antischistosomal activity. Future Med. Chem., 2015, 7(6), 801-820.
[] [PMID: 25996071]
Fallon, P.G.; Doenhoff, M.J. Drug-resistant schistosomiasis: Resistance to praziquantel and oxamniquine induced in Schistosoma mansoni in mice is drug specific. Am. J. Trop. Med. Hyg., 1994, 51(1), 83-88.
[] [PMID: 8059919]
Botros, S.S.; Bennett, J.L. Praziquantel Resistance. Expert Opin. Drug Discov., 2007, 2(sup1), S35-S40.
Wang, W.; Wang, L.; Liang, Y.S. Susceptibility or resistance of praziquantel in human schistosomiasis: A review. Parasitol. Res., 2012, 111(5), 1871-1877.
[] [PMID: 23052781]
Gryseels, B.; Mbaye, A.; De Vlas, S.J.; Stelma, F.F.; Guissé, F.; Van Lieshout, L.; Faye, D.; Diop, M.; Ly, A.; Tchuem-Tchuenté, L.A.; Engels, D.; Polman, K. Are poor responses to praziquantel for the treatment of Schistosoma mansoni infections in Senegal due to resistance? An overview of the evidence. Trop. Med. Int. Health, 2001, 6(11), 864-873.
[] [PMID: 11703840]
Duarte, C.D.; Barreiro, E.J.; Fraga, C.A. Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev. Med. Chem., 2007, 7(11), 1108-1119.
[] [PMID: 18045214]
Wang, L.; Guo, D-G.; Wang, Y-Y.; Zheng, C-Z. 4-Hydroxy-3-Methoxy-benzaldehyde series aroyl hydrazones: synthesis, thermostability and antimicrobial activities. RSC Advances, 2014, 4(102), 58895-58901.
Sapra, A.; Kumar, P.; Kakkar, S.; Narasimhan, B. Synthesis, antimicrobial evaluation and QSAR studies of p-hydroxy benzoic acid derivatives. Drug Res. (Stuttg.), 2014, 64(1), 17-22.
[PMID: 23950102]
Alam, M.S.; Lee, D.U. Synthesis, biological evaluation, drug-likeness, and in silico screening of novel benzylidene-hydrazone analogues as small molecule anticancer agents. Arch. Pharm. Res., 2016, 39(2), 191-201.
[] [PMID: 26694484]
Patel, J.M.; Dave, M.P.; Langalia, N.A.; Thaker, K.A. Studies on antitubercular agents. Preparation of 1-(4-Methoxybenzoyl)-2-benzalhydrazines and 2-Aryl-3-(4-Methoxybenzamido)-5-Carboxymethyl-4-Thiazolidinones. J. Indian Chem. Soc., 1985, 62(3), 254-255.
Bala, S.; Uppal, G.; Kamboj, S.; Saini, V.; Prasad, D.N. Design, characterization, computational studies, and pharmacological evaluation of substituted-N′-[(1E) substituted-phenylmethylidene]-benzohydrazide analogs. Med. Chem. Res., 2013, 22(6), 2755-2767.
Abdel-Rahman, R.M.; El-Gendy, Z.; Fawzy, M.M.; Mahmoud, M.B. Biologically active thiazolidinone. Part III. Synthesis and fungal toxicities of substituted thiazolidinone, thioether and n-benzoyl heterocyclic compounds from benzoic acid hydrazones. J. Indian Chem. Soc., 1991, 68(11), 628-631.
Rando, D.G.; Avery, M.A.; Tekwani, B.L.; Khan, S.I.; Ferreira, E.I. Antileishmanial activity screening of 5-nitro-2-heterocyclic benzylidene hydrazides. Bioorg. Med. Chem., 2008, 16(14), 6724-6731.
[] [PMID: 18571927]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[] [PMID: 6606682]
Mafud, A.C.; Silva, M.P.N.; Nunes, G.B.L.; de Oliveira, M.A.R.; Batista, L.F.; Rubio, T.I.; Mengarda, A.C.; Lago, E.M.; Xavier, R.P.; Gutierrez, S.J.C.; Pinto, P.L.S.; da Silva Filho, A.A.; Mascarenhas, Y.P.; de Moraes, J. Antiparasitic, structural, pharmacokinetic, and toxicological properties of riparin derivatives. Toxicol. In Vitro, 2018, 50, 1-10.
[] [PMID: 29476885]
De Moraes, J. Antischistosomal natural compounds: Present challenges for new drug screens. In: Current Topics in Tropical Medicine; Alfonso J. Rodriguez-Morales. Ed.;. IntechOpen, 2012.
Smithers, S.R.; Terry, R.J. The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of the adult worms. Parasitology, 1965, 55(4), 695-700.
[] [PMID: 4957633]
Silva, M.P.N.; Oliveira, G.L.S.; de Carvalho, R.B.F.; de Sousa, D.P.; Freitas, R.M.; Pinto, P.L.S.; de Moraes, J. Antischistosomal activity of the terpene nerolidol. Molecules, 2014, 19(3), 3793-3803.
[] [PMID: 24662089]
de Brito, M.R.M.; Peláez, W.J.; Faillace, M.S.; Militão, G.C.G.; Almeida, J.R.G.S.; Argüello, G.A.; Szakonyi, Z.; Fülöp, F.; Salvadori, M.C.; Teixeira, F.S.; Freitas, R.M.; Pinto, P.L.S.; Mengarda, A.C.; Silva, M.P.N.; Da Silva Filho, A.A.; de Moraes, J. Cyclohexene-fused 1,3-oxazines with selective antibacterial and antiparasitic action and low cytotoxic effects. Toxicol. In Vitro, 2017, 44, 273-279.
[] [PMID: 28755871]
Silva, M.P.; de Oliveira, R.N.; Mengarda, A.C.; Roquini, D.B.; Allegretti, S.M.; Salvadori, M.C.; Teixeira, F.S.; de Sousa, D.P.; Pinto, P.L.S.; da Silva Filho, A.A.; de Moraes, J. Antiparasitic activity of nerolidol in a mouse model of schistosomiasis. Int. J. Antimicrob. Agents, 2017, 50(3), 467-472.
[] [PMID: 28666754]
de Moraes, J.; de Oliveira, R.N.; Costa, J.P.; Junior, A.L.G.; de Sousa, D.P.; Freitas, R.M.; Allegretti, S.M.; Pinto, P.L.S. Phytol, a diterpene alcohol from chlorophyll, as a drug against neglected tropical disease Schistosomiasis mansoni. PLoS Negl. Trop. Dis., 2014, 8(1)e2617
[] [PMID: 24392173]
Silva, A.P.; Silva, M.P.; Oliveira, C.G.; Monteiro, D.C.; Pinto, P.L.; Mendonça, R.Z.; Costa Júnior, J.S.; Freitas, R.M.; de Moraes, J.; Garcinielliptone, F.C. Garcinielliptone FC: antiparasitic activity without cytotoxicity to mammalian cells. Toxicol. In Vitro, 2015, 29(4), 681-687.
[] [PMID: 25553916]
de Castro, C.C.B.; Costa, P.S.; Laktin, G.T.; de Carvalho, P.H.D.; Geraldo, R.B.; de Moraes, J.; Pinto, P.L.S.; Couri, M.R.C. Pinto, Pde.F.; Da Silva Filho, A.A. Cardamonin, a schistosomicidal chalcone from Piper aduncum L. (Piperaceae) that inhibits Schistosoma mansoni ATP diphosphohydrolase. Phytomedicine, 2015, 22(10), 921-928.
[] [PMID: 26321741]
Campelo, Y.D.M.; Mafud, A.C.; Véras, L.M.C.; Guimarães, M.A.; Yamaguchi, L.F.; Lima, D.F.; Arcanjo, D.D.R.; Kato, M.J.; Mendonça, R.Z.; Pinto, P.L.S.; Mascarenhas, Y.P.; Silva, M.P.N.; de Moraes, J.; Eaton, P.; de Souza de Almeida Leite, J.R. Synergistic effects of in vitro combinations of piplartine, epiisopiloturine and praziquantel against Schistosoma mansoni. Biomed. Pharmacother., 2017, 88, 488-499.
[] [PMID: 28126674]
Dias, M.M.; Zuza, O.; Riani, L.R.; de Faria Pinto, P.; Pinto, P.L.S.; Silva, M.P.; de Moraes, J.; Ataíde, A.C.Z.; de Oliveira Silva, F.; Cecílio, A.B.; Da Silva Filho, A.A. In vitro schistosomicidal and antiviral activities of Arctium lappa L. (Asteraceae) against Schistosoma mansoni and Herpes simplex virus-1. Biomed. Pharmacother., 2017, 94, 489-498.
[] [PMID: 28780467]
Quelemes, P.V.; Perfeito, M.L.G.; Guimarães, M.A.; dos Santos, R.C.; Lima, D.F.; Nascimento, C.; Silva, M.P.N.; Soares, M.J.D.S.; Ropke, C.D.; Eaton, P.; de Moraes, J.; Leite, J.R. Effect of neem (Azadirachta indica A. Juss) leaf extract on resistant Staphylococcus aureus biofilm formation and Schistosoma mansoni worms. J. Ethnopharmacol., 2015, 175, 287-294.
[] [PMID: 26408045]
de Moraes, J.; Dario, B.S.; Couto, R.A.A.; Pinto, P.L.S.; da Costa Ferreira, A.M. Antischistosomal activity of oxindolimine-metal complexes. Antimicrob. Agents Chemother., 2015, 59(10), 6648-6652.
[] [PMID: 26239976]
Mafud, A.C.; Silva, M.P.N.; Monteiro, D.C.; Oliveira, M.F.; Resende, J.G.; Coelho, M.L.; de Sousa, D.P.; Mendonça, R.Z.; Pinto, P.L.S.; Freitas, R.M.; Mascarenhas, Y.P.; de Moraes, J. Structural parameters, molecular properties, and biological evaluation of some terpenes targeting Schistosoma mansoni parasite. Chem. Biol. Interact., 2016, 244, 129-139.
[] [PMID: 26697994]
Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.A. Gaussian 09, Revision D.1; Gaussian, Inc.: Wallingford, CT, 2009.
Liu, X.; Ouyang, S.; Yu, B.; Liu, Y.; Huang, K.; Gong, J.; Zheng, S.; Li, Z.; Li, H.; Jiang, H. PharmMapper server: A web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res., 2010, 38(Web Server issue)(Suppl.2), W609-W614.
[] [PMID: 20430828]
Wang, X.; Shen, Y.; Wang, S.; Li, S.; Zhang, W.; Liu, X.; Lai, L.; Pei, J.; Li, H. PharmMapper 2017 update: A web server for potential drug target identification with a comprehensive target pharmacophore database. Nucleic Acids Res., 2017, 45(W1), W356-W360.
[] [PMID: 28472422]
Altschul, S.F.; Gish, W.; Miller, W.; Myers, E.W.; Lipman, D.J. Basic local alignment search tool. J. Mol. Biol., 1990, 215(3), 403-410.
[] [PMID: 2231712]
Wang, Q.; Pan, Y.; Wang, J.; Peng, Q.; Hongjun, L.; Zheng, J. Synthesis and biological activities of substituted N′-benzoylhydrazone derivatives. Afr. J. Biotechnol., 2011, 10(78), 18013-18021.
Taha, M.; Naz, H.; Rasheed, S.; Ismail, N.H.; Rahman, A.A.; Yousuf, S.; Choudhary, M.I. Synthesis of 4-methoxybenzoylhydrazones and evaluation of their antiglycation activity. Molecules, 2014, 19(1), 1286-1301.
[] [PMID: 24451249]
Lei, Y.; Li, T-Z.; Fu, C.; Guan, X-L.; Tan, Y. Synthesis and crystal structures of 4-Chloro-N′-(4-Hydroxy-3-Nitrobenzylidene)benzo-hydrazide monohydrate and 4-chloro-N′-(4-Hydroxy-3-methoxybenzylidene)benzohydrazide monohydrate. J. Chem. Crystallogr., 2011, 41(11), 1707-1711.
Palla, G.; Predieri, G.; Domiano, P.; Vignali, C.; Turner, W. Conformational behaviour and E/Z isomerization of N-Acyl and N-aroylhydrazones. Tetrahedron, 1986, 42(13), 3649-3654.
Syakaev, V.V.; Podyachev, S.N.; Buzykin, B.I.; Latypov, S.K.; Habicher, W.D.; Konovalov, A.I. NMR study of conformation and isomerization of Aryl- and Heteroarylaldehyde 4-Tert-butylphenoxyacetylhydrazones. J. Mol. Struct., 2006, 788(1–3), 55-62.
van Dijken, D.J.; Kovaříček, P.; Ihrig, S.P.; Hecht, S. Acylhydrazones as widely tunable photoswitches. J. Am. Chem. Soc., 2015, 137(47), 14982-14991.
[] [PMID: 26580808]
Mulvenna, J.; Moertel, L.; Jones, M.K.; Nawaratna, S.; Lovas, E.M.; Gobert, G.N.; Colgrave, M.; Jones, A.; Loukas, A.; McManus, D.P. Exposed proteins of the Schistosoma japonicum tegument. Int. J. Parasitol., 2010, 40(5), 543-554.
[] [PMID: 19853607]
Van Hellemond, J.J.; Retra, K.; Brouwers, J.F.H.M.; van Balkom, B.W.M.; Yazdanbakhsh, M.; Shoemaker, C.B.; Tielens, A.G.M. Functions of the tegument of schistosomes: clues from the proteome and lipidome. Int. J. Parasitol., 2006, 36(6), 691-699.
[] [PMID: 16545817]
Guimarães, M.A.; de Oliveira, R.N.; Véras, L.M.; Lima, D.F.; Campelo, Y.D.; Campos, S.A.; Kuckelhaus, S.A.; Pinto, P.L.; Eaton, P.; Mafud, A.C.; Mascarenhas, Y.P.; Allegretti, S.M.; de Moraes, J.; Lolić, A.; Verbić, T.; Leite, J.R. Anthelmintic activity in vivo of epiisopiloturine against juvenile and adult worms of Schistosoma mansoni. PLoS Negl. Trop. Dis., 2015, 9(3)e0003656
[] [PMID: 25816129]
de Lima, L.I.; Py-Daniel, K.R.; Guimarães, M.A.; Muehlmann, L.A.; Mafud, A.C.; Mascarenhas, Y.P.; Moraes, J.; de Souza de Almeida Leite, J.R.; Jiang, C.S.; Azevedo, R.B.; Figueiró Longo, J.P. Self-nanoemulsifying drug-delivery systems improve oral absorption and antischistosomal activity of epiisopiloturine. Nanomedicine (Lond.), 2018, 13(7), 689-702.
[] [PMID: 29564947]
Moraes, Jd.; Almeida, A.A.C.; Brito, M.R.M.; Marques, T.H.C.; Lima, T.C.; Sousa, D.P.; Nakano, E.; Mendonça, R.Z.; Freitas, R.M. Anthelmintic activity of the natural compound (+)-limonene epoxide against Schistosoma mansoni. Planta Med., 2013, 79(3-4), 253-258.
[] [PMID: 23408270]
Moraes, Jd.; Nascimento, C.; Lopes, P.O.M.V.; Nakano, E.; Yamaguchi, L.F.; Kato, M.J.; Kawano, T. Schistosoma mansoni: In vitro schistosomicidal activity of piplartine. Exp. Parasitol., 2011, 127(2), 357-364.
[] [PMID: 20832410]
de Moraes, J.; Nascimento, C.; Yamaguchi, L.F.; Kato, M.J.; Nakano, E. Schistosoma mansoni: in vitro schistosomicidal activity and tegumental alterations induced by piplartine on schistosomula. Exp. Parasitol., 2012, 132(2), 222-227.
[] [PMID: 22796749]
Aleixo de Carvalho, L.S.; Geraldo, R.B.; de Moraes, J.; Silva Pinto, P.L.; de Faria Pinto, P. Pereira, Odos.S., Jr; Da Silva Filho, A.A. Schistosomicidal activity and docking of Schistosoma mansoni ATPDase 1 with licoflavone B isolated from Glycyrrhiza inflata (Fabaceae). Exp. Parasitol., 2015, 159, 207-214.
[] [PMID: 26454044]
Bahia, D.; Andrade, L.F.; Ludolf, F.; Mortara, R.A.; Oliveira, G. Protein tyrosine kinases in Schistosoma mansoni. Mem. Inst. Oswaldo Cruz, 2006, 101(May)(Suppl. 1), 137-143.
[] [PMID: 17308761]
Andrade, L.F.; Nahum, L.A.; Avelar, L.G.; Silva, L.L.; Zerlotini, A.; Ruiz, J.C.; Oliveira, G. Eukaryotic protein kinases (ePKs) of the helminth parasite Schistosoma mansoni. BMC Genomics, 2011, 12, 215.
[] [PMID: 21548963]
Davies, S.J.; Shoemaker, C.B.; Pearce, E.J. A divergent member of the transforming growth factor beta receptor family from Schistosoma mansoni is expressed on the parasite surface membrane. J. Biol. Chem., 1998, 273(18), 11234-11240.
[] [PMID: 9556614]
Ardito, F.; Giuliani, M.; Perrone, D.; Troiano, G.; Lo Muzio, L. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy. (Review). Int. J. Mol. Med., 2017, 40(2), 271-280.
[] [PMID: 28656226]
Hsu, V.; Zobel, C.L.; Lambie, E.J.; Schedl, T.; Kornfeld, K. Caenorhabditis elegans lin-45 raf is essential for larval viability, fertility and the induction of vulval cell fates. Genetics, 2002, 160(2), 481-492.
[PMID: 11861555]
Maetani, M.; Kato, N.; Jabor, V.A.P.; Calil, F.A.; Nonato, M.C.; Scherer, C.A.; Schreiber, S.L. Discovery of antimalarial azetidine-2-carbonitriles that inhibit P. falciparum dihydroorotate dehydrogenase. ACS Med. Chem. Lett., 2017, 8(4), 438-442.
[] [PMID: 28435533]
Padua, R.A.P.; Tomaleri, G.P.; Reis, R.A.G.; David, J.S.; Silva, V.C.; Pinheiro, M.P.; Nonato, M.C. ThermoFMN - A thermofluor assay developed for ligand-screening as an alternative strategy for drug discovery. J. Braz. Chem. Soc., 2014, 25(10), 1864-1871.
Reis, R.A.G.; Calil, F.A.; Feliciano, P.R.; Pinheiro, M.P.; Nonato, M.C. The dihydroorotate dehydrogenases: Past and present. Arch. Biochem. Biophys., 2017, 632, 175-191.
[] [PMID: 28666740]
Hansen, M.; Le Nours, J.; Johansson, E.; Antal, T.; Ullrich, A.; Löffler, M.; Larsen, S. Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Sci., 2004, 13(4), 1031-1042.
[] [PMID: 15044733]
Hill, B.; Kilsby, J.; Rogerson, G.W.; McIntosh, R.T.; Ginger, C.D. The enzymes of pyrimidine biosynthesis in a range of parasitic protozoa and helminths. Mol. Biochem. Parasitol., 1981, 2(3-4), 123-134.
[] [PMID: 6111750]
el Kouni, M.H. Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets. Comp. Biochem. Physiol. B Biochem. Mol. Biol., 2017, 213, 55-80.
Lorsuwannarat, N.; Saowakon, N.; Ramasoota, P.; Wanichanon, C.; Sobhon, P. The anthelmintic effect of plumbagin on Schistosoma mansoni. Exp. Parasitol., 2013, 133(1), 18-27.
[] [PMID: 23085370]
Braschi, S.; Borges, W.C.; Wilson, R.A. Proteomic analysis of the schistosome tegument and its surface membranes. Mem. Inst. Oswaldo Cruz, 2006, 101(Suppl.), 205-212.
Kardoush, M.I.; Ward, B.J.; Ndao, M. Serum carbonic anhydrase 1 is a biomarker for diagnosis of human Schistosoma mansoni Infection. Am. J. Trop. Med. Hyg., 2017, 96(4), 842-849.
[] [PMID: 28500821]
Castro-Borges, W.; Dowle, A.; Curwen, R.S.; Thomas-Oates, J.; Wilson, R.A. Enzymatic shaving of the tegument surface of live schistosomes for proteomic analysis: A rational approach to select vaccine candidates. PLoS Negl. Trop. Dis., 2011, 5(3)e993
[] [PMID: 21468311]
Wilson, R.A.; Wright, J.M.; de Castro-Borges, W.; Parker-Manuel, S.J.; Dowle, A.A.; Ashton, P.D.; Young, N.D.; Gasser, R.B.; Spithill, T.W. Exploring the Fasciola hepatica tegument proteome. Int. J. Parasitol., 2011, 41(13-14), 1347-1359.
[] [PMID: 22019596]
You, H.; Liu, C.; Du, X.; McManus, D.P. Acetylcholinesterase and nicotinic acetylcholine receptors in schistosomes and other parasitic helminths. Molecules, 2017, 22(9), 1550.
[] [PMID: 28906438]
Caby, S.; Pagliazzo, L.; Lancelot, J.; Saliou, J.M.; Bertheaume, N.; Pierce, R.J.; Roger, E. Analysis of the interactome of Schistosoma mansoni histone deacetylase 8. PLoS Negl. Trop. Dis., 2017, 11(11)e0006089
[] [PMID: 29155817]
Hai, Y.; Edwards, J.E.; Van Zandt, M.C.; Hoffmann, K.F.; Christianson, D.W. Crystal structure of Schistosoma mansoni arginase, A potential drug target for the treatment of schistosomiasis. Biochemistry, 2014, 53(28), 4671-4684.
[] [PMID: 25007099]
Sotillo, J.; Pearson, M.; Becker, L.; Mulvenna, J.; Loukas, A. A quantitative proteomic analysis of the tegumental proteins from Schistosoma mansoni schistosomula reveals novel potential therapeutic targets. Int. J. Parasitol., 2015, 45(8), 505-516.
[] [PMID: 25910674]
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Year: 2019
Page: [1241 - 1251]
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DOI: 10.2174/1568026619666190620163237
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