ATP-Diphosphohydrolases in Parasites: Localization, Functions and Recent Developments in Drug Discovery

Author(s): Lara Soares Aleixo de Carvalho, Ismael José Alves Junior, Lauriene Ricardo Junqueira, Lívia Mara Silva, Lorena Rodrigues Riani, Priscila de Faria Pinto, Ademar Alves Da Silva Filho*

Journal Name: Current Protein & Peptide Science

Volume 20 , Issue 9 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


ATP-diphosphohydrolases (EC, also known as ATPDases, NTPases, NTPDases, EATPases or apyrases, are enzymes that hydrolyze a variety of nucleoside tri- and diphosphates to their respective nucleosides, being their activities dependent on the presence of divalent cations, such as calcium and magnesium. Recently, ATP-diphosphohydrolases were identified on the surface of several parasites, such as Trypanosoma sp, Leishmania sp and Schistosoma sp. In parasites, the activity of ATPdiphosphohydrolases has been associated with the purine recuperation and/or as a protective mechanism against the host organism under conditions that involve ATP or ADP, such as immune responses and platelet activation. These proteins have been suggested as possible targets for the development of new antiparasitic drugs. In this review, we will comprehensively address the main aspects of the location and function of ATP-diphosphohydrolase in parasites. Also, we performed a detailed research in scientific database of recent developments in new natural and synthetic inhibitors of the ATPdiphosphohydrolases in parasites.

Keywords: ATP-diphosphohydrolase, apyrase, parasite, ATPDases, inhibitors, NTPDase, ecto-nucleotidases.

Dou, L.; Chen, Y.F.; Cowan, P.J.; Chen, X.P. Extracellular ATP signaling and clinical relevance. Clin. Immunol., 2018, 188, 67-73.
Knowles, A.F. The GDA1-CD39 superfamily: NTPDases with diverse functions. Purinergic Signal., 2011, 7(1), 21-45.
Al-Rashida, M.; Iqbal, J. Therapeutic potentials of ecto-nucleoside triphosphate diphosphohydrolase, ecto-nucleotide pyrophosphatase/phospho-diesterase, ecto-5′-nucleotidase, and alkaline phosphatase inhibitors. Med. Res. Rev., 2014, 34(4), 703-743.
Dias, D.A.; de Barros Penteado, B.; dos Santos, L.D.; dos Santos, P.M.; Arruda, C.C.P.; Schetinger, M.R.C.; Leal, D.B.R.; dos Santos Jaques, J.A. Characterization of Ectonucleoside Triphosphate Diphosphohydrolase (E-NTPDase; EC activity in mouse peritoneal cavity cells. Cell Biochem. Funct., 2017, 35(7), 358-363.
Al-Rashida, M.; Qazi, S.U.; Batool, N.; Hameed, A.; Iqbal, J. Ectonucleotidase inhibitors: A patent review (2011-2016). Expert Opin. Ther. Pat., 2017, 27(12), 1291-1304.
Allard, B.; Longhi, M.S.; Robson, S.C.; Stagg, J. The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets. Immunol. Rev., 2017, 276(1), 121-144.
Silverman, J.A.; Qi, H.; Riehl, A.; Beckers, C.; Nakaar, V.; Joiner, K.A. Induced activation of the Toxoplasma gondii nucleoside triphosphate hydrolase leads to depletion of host cell atp levels and rapid exit of intracellular parasites from infected cells. J. Biol. Chem., 1998, 273(20), 12352-12359.
Nakaar, V.; Samuel, B.U.; Ngo, E.O.; Joiner, K.A. Targeted reduction of nucleoside triphosphate hydrolase by antisense RNA inhibits Toxoplasma gondii Proliferation. J. Biol. Chem., 1999, 274(8), 5083-5087.
Santos, R.F.; Pôssa, M.A.S.; Bastos, M.S.; Guedes, P.M.M.; Almeida, M.R.; DeMarco, R.; Verjovski-Almeida, S.; Bahia, M.T.; Fietto, J.L.R. Influence of ecto-nucleoside triphosphate diphosphohydrolase activity on Trypanosoma cruzi infectivity and virulence. PLoS Negl. Trop. Dis., 2009, 3(3), e387.
Bisaggio, D.F.R.; Peres-Sampaio, C.E.; Meyer-Fernandes, J.R.; Souto-Padrón, T. Ecto-ATPase activity on the surface of Trypanosoma cruzi and its possible role in the parasite-host cell interaction. Parasitol. Res., 2003, 91(4), 273-282.
Barros, F.S.; De Menezes, L.F.; Pinheiro, A.A.S.; Silva, E.F.; Lopes, A.H.C.S.; De Souza, W.; Meyer-Fernandes, J.R. Ectonucleotide diphosphohydrolase activities in Entamoeba histolytica. Arch. Biochem. Biophys., 2000, 375(2), 304-314.
Berrêdo-Pinho, M.; Peres-Sampaio, C.E.; Chrispim, P.P.M.; Belmont-Firpo, R.; Lemos, A.P.; Martiny, A.; Vannier-Santos, M.A.; Meyer-Fernandes, J.R. A mg-dependent ecto-ATPase in Leishmania amazonensis and its possible role in adenosine acquisition and virulence. Arch. Biochem. Biophys., 2001, 391(1), 16-24.
Fietto, J.L.R.; DeMarco, R.; Nascimento, I.P.; Castro, I.M.; Carvalho, T.M.U.; De Souza, W.; Bahia, M.T.; Alves, M.J.M.; Verjovski-Almeida, S. Characterization and immunolocalization of an NTP diphosphohydrolase of Trypanosoma cruzi. Biochem. Biophys. Res. Commun., 2004, 316(2), 454-460.
Baqi, Y. Ecto-nucleotidase inhibitors: Recent developments in drug discovery. Mini Rev. Med. Chem., 2015, 15(1), 21-33.
Robson, S.C.; Sévigny, J.; Zimmermann, H. The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance. Purinergic Signal., 2006, 2(2), 409-430.
Flores-Herrera, O.; Uribe, A.; Pardo, J.P.; Rendón, J.L.; Martinez, F. A novel ATP-diphosphohydrolase from human term placental mitochondria. Placenta, 1999, 20(5-6), 475-484.
Robson, S.C.; Wu, Y.; Sun, X.; Knosalla, C.; Dwyer, K.; Enjyoji, K. Ectonucleotidases of CD39 family modulate vascular inflammation and thrombosis in transplantation. Semin. Thromb. Hemost., 2005, 31(2), 217-233.
Leclerc, M.C.; Grondin, G.; Gendron, F.P.; Sévigny, J.; Beaudoin, A.R. Identification, characterization, and immunolocalization of a nucleoside triphosphate diphosphohydrolase in pig liver. Arch. Biochem. Biophys., 2000, 377(2), 372-378.
Kaczmarek, E.; Koziak, K.; Sévigny, J.; Siegel, J.B.; Anrather, J.; Beaudoin, A.R.; Bach, F.H.; Robson, S.C. Identification and characterization of CD39/vascular ATP diphosphohydrolase. J. Biol. Chem., 1996, 271(51), 33116-33122.
Handa, M.; Guidotti, G. Purification and cloning of a soluble ATP-diphosphohydrolase (Apyrase) from potato tubers (Solanum tuberosum). Biochem. Biophys. Res. Commun., 1996, 218(3), 916-923.
Steinebrunner, I.; Jeter, C.; Song, C.; Roux, S.J. Molecular and biochemical comparison of two different apyrases from Arabidopsis thaliana. Plant Physiol. Biochem., 2000, 38(12), 913-922.
Bermudes, D.; Peck, K.R.; Afifi, M.A.; Beckers, C.J.M.; Joiner, K.A. Tandemly repeated genes encode nucleoside triphosphate hydrolase isoforms secreted into the parasitophorous vacuole of Toxoplasma gondii. J. Biol. Chem., 1994, 269(46), 29252-29260.
Coimbra, E.S.; Gonçalves-Da-Costa, S.C.; Corte-Real, S.; De Freitas, F.G.R.; Durão, A.C.; Souza, C.S.F.; Silva-Santos, M.I.; Vasconcelos, E.G. Characterization and cytochemical localization of an ATP diphosphohydrolase from Leishmania amazonensis promastigotes. Parasitology, 2002, 124(2), 137-143.
Sansom, F.M.; Robson, S.C.; Hartland, E.L. Possible effects of microbial ecto-nucleoside triphosphate diphosphohydrolases on host-pathogen interactions. Microbiol. Mol. Biol. Rev., 2008, 72(4), 765-781.
De Aguiar Matos, J.A.; Borges, F.P.; Tasca, T.; Bogo, M.R.; De Carli, G.A.; Da Graça Fauth, M.; Dias, R.D.; Bonan, C.D. Characterisation of an ATP diphosphohydrolase (Apyrase, EC activity in Trichomonas vaginalis. Int. J. Parasitol., 2001, 31(8), 770-775.
Dos Passos Lemos, A.; Acacia de Sá Pinheiro, A.; Berrêdo-Pinho, M.; Fonseca de Souza, A.L.; Motta, M.M.; De Souza, W.; Meyer-Fernandes, J.R. Ectonucleotide diphosphohydrolase activity in Crithidia deanei. Parasitol. Res., 2002, 88(10), 905-911.
Vasconcelos, E.G.; Nascimento, P.S.; Nazareth, M.; Meirelles, L.; Verjovski-Almeida, S.; Ferreira, S.T. Characterization and localization of an ATP-diphosphohydrolase on the external surface of the tegument of Schistosoma mansoni. Mol. Biochem. Parasitol., 1993, 58(2), 205-214.
Guevara-Flores, A.; Olvera-Sánchez, S.; Gómez-Concha, C.; Juárez, O.; Esparza-Perusquía, M.; Pardo, J.P.; Mendoza-Hernández, G.; Martínez, F.; Flores-Herrera, O. 5′-P-Fluorosulfonyl benzoyl adenosine inhibits an ecto-ATP-diphosphohydrolase in the tegument surface of Taenia crassiceps cysticerci. Mol. Biochem. Parasitol., 2008, 162(2), 123-133.
Sansom, F.M.; Newton, H.J.; Crikis, S.; Cianciotto, N.P.; Cowan, P.J.; D’Apice, A.J.F.; Hartland, E.L. A bacterial ecto-triphosphate diphosphohydrolase similar to human CD39 is essential for intracellular multiplication of Legionella pneumophila. Cell. Microbiol., 2007, 9(8), 1922-1935.
Vasconcelos, E.G.; Ferreira, S.T.; De Carvalho, T.M.U.; De Souza, W.; Kettlun, A.M.; Mancilla, M.; Valenzuela, M.A.; Verjovski-Almeida, S. Partial purification and immunohistochemical localization of ATP diphosphohydrolase from Schistosoma mansoni: Immunological cross-reactivities with potato apyrase and Toxoplasma gondii nucleoside triphosphate hydrolase. J. Biol. Chem., 1996, 271(36), 22139-22145.
Gryseels, B.; Polman, K.; Clerinx, J.; Kestens, L. Human schistosomiasis. Lancet, 2006, 368(9541), 1106-1118.
De Souza, V.C.; Nunes, V.S.; Vasconcelos, E.G.; De Faria Pinto, P.; Capriles, P. Structural comparative analysis of secreted NTPDase models of Schistosoma mansoni and Homo sapiens. In Lecture Notes in Computer Science; Springer, Cham 2014; Vol. 8826, pp. 91-98
DeMarco, R.; Kowaltowski, A.T.; Mortara, R.A.; Verjovski-Almeida, S. Molecular Characterization and immunolocalization of Schistosoma mansoni ATP-diphosphohydrolase. Biochem. Biophys. Res. Commun., 2003, 307(4), 831-838.
De Faria Pinto, P.; Meirelle, M.N.L.; Lenzi, H.L.; Mota, E.M.; Penido, M.L.O.; Coelho, P.M.Z.; Vasconcelos, E.G. ATP diphosphohydrolase from Schistosoma mansoni egg: Characterization and immunocytochemical localization of a new antigen. Parasitology, 2004, 129(1), 51-57.
Braschi, S.; Wilson, R.A. Proteins exposed at the adult schistosome surface revealed by biotinylation. Mol. Cell. Proteomics, 2006, 5(2), 347-356.
Braschi, S.; Curwen, R.S.; Ashton, P.D.; Verjovski-Almeida, S.; Wilson, A. The tegument surface membranes of the human blood parasite Schistosoma mansoni: A proteomic analysis after differential extraction. Proteomics, 2006, 6(5), 1471-1482.
Levano-Garcia, J.; Mortara, R.A.; Verjovski-Almeida, S.; DeMarco, R. Characterization of Schistosoma mansoni ATPDase2 gene, a novel apyrase family member. Biochem. Biophys. Res. Commun., 2007, 352(2), 384-389.
Bhardwaj, R.; Skelly, P.J. Purinergic signaling and immune modulation at the schistosome surface? Trends Parasitol., 2009, 25(6), 256-260.
Da’dara, A.A.; Bhardwaj, R.; Ali, Y.B.M.; Skelly, P.J. Schistosome tegumental ecto-apyrase (SmATPDase1) degrades exogenous pro-inflammatory and pro-thrombotic nucleotides. PeerJ, 2014, 2, e316.
Da’dara, A.A.; Bhardwaj, R.; Skelly, P.J. Schistosome apyrase SmATPDase1, but Not SmATPDase2, hydrolyses exogenous ATP and ADP. Purinergic Signal., 2014, 10(4), 573-580.
Sibley, L.D.; Khan, A.; Ajioka, J.W.; Rosenthal, B.M. Genetic diversity of Toxoplasma gondii in animals and humans. Philos. Trans. R. Soc. B Biol. Sci., 2009, 364(1530), 2749-2761.
Asai, T.; O’Sullivan, W.J.; Tatibana, M. A potent nucleoside triphosphate hydrolase from the parasitic protozoan Toxoplasma gondii. Purification, some properties, and activation by thiol compounds. J. Biol. Chem., 1983, 258(11), 6816-6822.
Asai, T.; Miura, S.; Sibley, L.D.; Okabayashi, H.; Takeuchi, T. Biochemical and molecular characterization of nucleoside triphosphate hydrolase isozymes from the parasitic protozoan Toxoplasma gondii. J. Biol. Chem., 1995, 270(19), 11391-11397.
Kikuchi, T.; Furuta, T.; Kojima, S. Membrane localization and demonstration of isoforms of nucleoside triphosphate hydrolase from Toxoplasma gondii. Parasitology, 2001, 122(1), 15-23.
Nakaar, V.; Beckers, C.J.M.; Polotsky, V.; Joiner, K.A. Basis for substrate specificity of the Toxoplasma gondii nucleoside triphosphate hydrolase. Mol. Biochem. Parasitol., 1998, 97(1-2), 209-220.
Nakaar, V.; Bermudes, D.; Peck, K.R.; Joiner, K.A. Upstream elements required for expression of nucleoside triphosphate hydrolase genes of Toxoplasma gondii. Mol. Biochem. Parasitol., 1998, 92(2), 229-239.
Tan, F.; Hu, X.; Pan, C.W.; Ding, J.Q.; Chen, X.G. Monoclonal antibodies against nucleoside triphosphate hydrolase-II can reduce the replication of Toxoplasma gondii. Parasitol. Int., 2010, 59(2), 141-146.
Vera-Izaguirre, D.S.; Vega-Memije, E.; Quintanilla-Cedillo, M.R.; Arenas, R. Leishmaniasis revisión. Dermatologia Cosmet. Medica y Quir., 2006, 4(4), 252-260.
Torres-Guerrero, E.; Quintanilla-Cedillo, M.R.; Ruiz-Esmenjaud, J.; Arenas, R. Leishmaniasis: A review. F1000 Res., 2017, 6, 750.
Azulay, R.D.; Azulay, D.R.; Azulay-Abulafia, L. Dermatologia, 7th ed.; Guanabara Koogan: Rio de Janeiro 2017.
Sansom, F.M. The role of the NTPDase enzyme family in parasites: What do we know, and where to from here? Parasitology, 2012, 139(8), 963-980.
Vasconcellos, R.D.S.; Mariotini-Moura, C.; Gomes, R.S.; Serafim, T.D.; Firmino, R. de C.; Silva e Bastos, M.; Castro, F.F. de; De Oliveira, C.M.; Borges-Pereira, L.; De Souza, A.C.A.; De Souza, R.F.; Gómez, G.A.T.; Pinheiro, A. da C.; Maciel, T.E.F.; Silva-Júnior, A.; Bressan, G.C.; Almeida, M.R.; Baqui, M.M.A.; Afonso, L.C.C.; Fietto, J.L.R. Leishmania infantum ecto-nucleoside triphosphate diphosphohydrolase-2 is an apyrase involved in macrophage infection and expressed in infected dogs. PLoS Negl. Trop. Dis., 2014, 8(11), e3309.
Detoni, M.L.; Fessel, M.R.; Maia, A.C.; Porcino, G.N.; Quellis, L.R.; Faria-Pinto, P.; Marques, M.J.; Juliano, M.A.; Juliano, L.; Diniz, V.A.; Côrte-Real, S.; Gonçalves-da-Costa, S.C.; Souza, C.S.; Vasconcelos, E.G. An antigenic domain of the Leishmania amazonensis nucleoside triphosphate diphosphohydrolase (NTPDase 1) is associated with disease progression in susceptible infected mice. Parasitol. Res., 2013, 112(8), 2773-2782.
Meyer-Fernandes, J.R.; Cosentino-Gomes, D.; Vieira, D.P.; Lopes, A.H.C.S. Ecto-nucleoside triphosphate diphosphohydrolase activities in trypano- somatids: Possible roles in infection, virulence and purine recycling. Open Parasitol. J., 2010, 4(4), 116-119.
Meyer-Fernandes, J.R.; Dutra, P.M.L.; Rodrigues, C.O.; Saad-Nehme, J.; Lopes, A.H.C.S. Mg-dependent ecto-ATPase activity in Leishmania tropica. Arch. Biochem. Biophys., 1997, 341(1), 40-46.
Rezende-Soares, F.A.; Carvalho-Campos, C.; Marques, M.J.; Porcino, G.N.; Giarola, N.L.L.; Costa, B.L.S.; Taunay-Rodrigues, A.; De Faria Pinto, P.; Souza, M.A.; Diniz, V.Á.; Corte-Real, S.; Juliano, M.A.; Juliano, L.; Vasconcelos, E.G. Cytochemical localization of ATP diphosphohydrolase from Leishmania (Viannia) braziliensis promastigotes and identification of an antigenic and catalytically active isoform. Parasitology, 2010, 137(5), 773-783.
Sinha, P.; Paswan, R.K.; Kumari, A.; Kumar, S.; Bimal, S.; Das, P.; Lal, C.S. Magnesium-dependent ecto-ATP diphosphohydrolase activity in Leishmania donovani. Curr. Microbiol., 2016, 73(6), 811-819.
Meyer-Fernandes, J.R.; Saad-Nehme, J.; Peres-Sampaio, C.E.; Belmont-Firpo, R.; Bisaggio, D.F.R.; Do Couto, L.C.; Fonseca De Souza, A.L.; Lopes, A.H.C.S.; Souto-Padrón, T. A Mg-dependent ecto-ATPase is increased in the infective stages of Trypanosoma cruzi. Parasitol. Res., 2004, 93(1), 41-50.
Fonseca, F.V.; Fonseca De Souza, A.L.; Mariano, A.C.; Entringer, P.F.; Gondim, K.C.; Meyer-Fernandes, J.R. Trypanosoma rangeli: Characterization of a Mg-dependent ecto ATP-diphosphohydrolase activity. Exp. Parasitol., 2006, 112(2), 76-84.
Stemmer, S.M.; Mordechai, E.; Adelson, M.E.; Gygax, S.E.; Hilbert, D.W. Trichomonas vaginalis is most frequently detected in women at the age of peri-/premenopause: An unusual pattern for a sexually transmitted pathogen Am. J. Obstet. Gynecol, 2018. 218(3), 328e1-328e13
Hosny, A.E.D.M.S.; El-khayat, W.; Kashef, M.T.; Fakhry, M.N. Association between preterm labor and genitourinary tract infections caused by Trichomonas vaginalis, Mycoplasma hominis, gram-negative bacilli, and coryneforms. J. Chinese. Med. Assoc., 2017, 80(9), 575-581.
Gong, Y-H.; Liu, Y.; Li, P.; Zhu, Z-J.; Hong, Y.; Fu, G-H.; Xue, Y-J.; Xu, C.; Li, Z. A Nonobstructive azoospermic patient with Trichomonas vaginalis infection in testes. Asian J. Androl., 2018, 20(1), 97-98.
Tsevat, D.G.; Wiesenfeld, H.C.; Parks, C.; Peipert, J.F. Sexually transmitted diseases and infertility. Am. J. Obstet. Gynecol., 2017, 216(1), 1-9.
Cherpes, T.L.; Wiesenfeld, H.C.; Melan, M.A.; Kant, J.A.; Cosentino, L.A.; Meyn, L.A.; Hillier, S.L. The associations between pelvic inflammatory disease, Trichomonas vaginalis infection, and positive Herpes simplex virus type 2 serology. Sex. Transm. Dis., 2006, 33(12), 747-752.
Taylor, B.D.; Darville, T.; Haggerty, C.L. Does bacterial vaginosis cause pelvic inflammatory disease? Sex. Transm. Dis., 2013, 40(2), 117-122.
Lazenby, G.B.; Taylor, P.T.; Badman, B.S.; McHaki, E.; Korte, J.E.; Soper, D.E.; Young Pierce, J. An association between Trichomonas vaginalis and high-risk human papillomavirus in rural tanzanian women undergoing cervical cancer screening. Clin. Ther., 2014, 36(1), 38-45.
De Jesus, J.B.; De Sá Pinheiro, A.A.; Lopes, A.H.C.S.; Meyer-Fernandes, J.R. An ectonucleotide ATP-diphosphohydrolase activity in Trichomonas vaginalis stimulated by galactose and its possible role in virulence. Zeitschrift fur Naturforsch. - Sect. C J. Biosci., 2002, 57(9-10), 890-896.
Frasson, A.P.; Dos Santos, O.; Meirelles, L.C.; Macedo, A.J.; Tasca, T. Five putative nucleoside triphosphate diphosphohydrolase genes are expressed in Trichomonas vaginalis. FEMS Microbiol. Lett., 2016, 363(2), fnv221.
Tasca, T.; Bonan, C.D.; De Carli, G.A.; Sarkis, J.J.F. Trichomonas vaginalis: Cytochemical localization of a ntpdase1 and an ecto-5′-nucleotidase and effects of adenine nucleotides on cellular viability. Parasitol. Res., 2004, 93(4), 300-303.
Frasson, A.P.; De Carli, G.A.; Bonan, C.D.; Tasca, T. Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis. Purinergic Signal., 2012, 8(1), 1-9.
De Jesus, J.B.; Ferreira, M.A.; Cuervo, P.; Britto, C.; Costa e Silva-Filho, F.; Roberto Meyer-Fernandes, J. Iron modulates ecto-phosphohydrolase activities in pathogenic trichomonads. Parasitol. Int., 2006, 55(4), 285-290.
Borges, F.P.; De Brum Vieira, P.; Wiltuschnig, R.C.M.; Tasca, T.; De Carli, G.A.; Bonan, C.D. Characterization of nucleoside triphosphate diphosphohydrolase activity in Trichomonas gallinae and the influence of penicillin and streptomycin in extracellular nucleotide hydrolysis. FEMS Microbiol. Lett., 2008, 283(2), 189-195.
Benchimol, M. The nuclei of Giardia lamblia - new ultrastructural observations. Arch. Microbiol., 2005, 183(3), 160-168.
Lin, B.C.; Su, L.H.; Weng, S.C.; Pan, Y.J.; Chan, N.L.; Li, T.K.; Wang, H.C.; Sun, C.H. DNA topoisomerase II is involved in regulation of cyst wall protein genes and differentiation in Giardia lamblia. PLoS Negl. Trop. Dis., 2013, 7(5), e2218.
Pinheiro, A.A. de S.; Cosentino-Gomes, D.; Lanfredi-Rangel, A.; Ferraro, R.B.; Souza, W De; Meyer-Fernandes, J.R. Giardia lamblia: Biochemical characterization of an ecto-ATPase activity. Exp. Parasitol., 2008, 119(2), 279-284.
Carpio, A. Neurocysticercosis: An update. Lancet Infect. Dis., 2002, 2(12), 751-762.
Higa, A.I.; Cazzulo, J.J. Mg2+-activated adenosine triphosphatase from Crithidia fasciculata: Purification and inhibition by suramin and efrapeptin. Mol. Biochem. Parasitol., 1981, 3(6), 357-367.
Opperdoes, F.R.; De Ruke, D.; Borst, P. Reactions involved in energy transfer in trypanosomes-I. characterization of the mitochondrial adenine nucleotide translocator and the ATPase of Crithidia luciliae. Comp. Biochem. Physiol.-Part B Biochem., 1976, 54(1), 7-12.
Gendron, F.P.; Halbfinger, E.; Fischer, B.; Duval, M.; D’Orléans-Juste, P.; Beaudoin, A.R. Novel inhibitors of nucleoside triphosphate diphosphohydrolases: Chemical synthesis and biochemical and pharmacological characterizations. J. Med. Chem., 2000, 43(11), 2239-2247.
Müller, C.E.; Iqbal, J.; Baqi, Y.; Zimmermann, H.; Röllich, A.; Stephan, H. Polyoxometalates-a New Class of Potent Ecto-Nucleoside Triphosphate Diphosphohydrolase (NTPDase) Inhibitors. Bioorganic. Med. Chem. Lett., 2006, 16(23), 5943-5947.
Andrade, S.F.; Da Silva Filho, A.A.; Resende, D.D.O.; Silva, M.L.A.; Cunha, W.R.; Nanayakkara, N.P.D.; Bastos, J.K. Antileishmanial, antimalarial and antimicrobial activities of the extract and isolated compounds from Austroplenckia populnea (celastraceae). Zeitschrift fur Naturforsch. - Sect. C J. Biosci., 2008, 63(7-8), 497-502.
Parreira, N.A.; Magalhães, L.G.; Morais, D.R.; Caixeta, S.C.; De Sousa, J.P.B.; Bastos, J.K.; Cunha, W.R.; Silva, M.L.A.; Nanayakkara, N.P.D.; Rodrigues, V.; Da Silva Filho, A.A. Antiprotozoal, schistosomicidal, and antimicrobial activities of the essential oil from the leaves of Baccharis dracunculifolia. Chem. Biodivers., 2010, 7(4), 993-1001.
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, P.D.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.
De Carvalho, L.S.A.; Geraldo, R.B.; De Moraes, J.; Silva Pinto, P.L.; De Faria Pinto, P.; Pereira, O. dos S.; 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.
De Almeida, L.M.S.; De Carvalho, L.S.A.; Gazolla, M.C.; Silva Pinto, P.L.; Silva, M.P.N. Da; De Moraes, J.; Da Silva Filho, A.A. Flavonoids and sesquiterpene lactones from Artemisia absinthium and Tanacetum parthenium against Schistosoma mansoni worms. Evidence-based Complement. Altern. Med., 2016, 2016, 9521349.
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.
Souza, R.L.; Gonçalves, U.O.; Badoco, F.R.; De Souza Galvão, L.; Santos, R.A. dos; De Carvalho, P.H.D.; De Carvalho, L.S.A.; Da Silva Filho, A.A.; Veneziani, R.C.S.; Rodrigues, V.; Ambrósio, S.R.; Magalhães, L.G. Licochalcone a induces morphological and biochemical alterations in Schistosoma mansoni adult worms. Biomed. Pharmacother., 2017, 96, 64-71.
Pereira, V.R.D.; Junior, I.J.A.; Silveira, L.S.; Geraldo, R.B.; Faria-Pinto, P.; Teixeira, F.S.; Salvadori, M.C.; Silva, M.P.; Alves, L.A.; Capriles, P.V.S.Z.; Almeida, A.C.; Coimbra, E.S.; Pinto, P.L.S.; Couri, M.R.C.; de Moraes, J.; Da Silva Filho, A.A. In vitro and in vivo antischistosomal activities of chalcones. Chem. Biodivers., 2018, 15(12), e1800398.
Bastida, J.; Lavilla, R.; Viladomat, F. Chemical and biological aspects of narcissus alkaloids.In: Alkaloids: Chemistry and Biology; Academic Press, 2006, Vol. 63, pp. 87-179.
Heinrich, M.; Teoh, H.L. Galanthamine from snowdrop - the development of a modern drug against Alzheimer’s disease from local caucasian knowledge. J. Ethnopharmacol., 2004, 92(2-3), 147-162.
Arrigoni, O.; Paciolla, C.; De Gara, L. Inhibition of galactonolactone dehydrogenase activity by lycorine. Boll. Soc. Ital. Biol. Sper., 1996, 72(1-2), 37-43.
Giordani, R.B.; Weizenmann, M.; Rosemberg, D.B.; De Carli, G.A.; Bogo, M.R.; Zuanazzi, J.A.S.; Tasca, T. Trichomonas vaginalis nucleoside triphosphate diphosphohydrolase and ecto-5′-nucleotidase activities are inhibited by lycorine and candimine. Parasitol. Int., 2010, 59(2), 226-231.
Schepetkin, I.A.; Kirpotina, L.N.; Mitchell, P.T.; Kishkentaeva, A.S.; Shaimerdenova, Z.R.; Atazhanova, G.A.; Adekenov, S.M.; Quinn, M.T. The natural sesquiterpene lactones arglabin, grosheimin, agracin, parthenolide, and estafiatin inhibit T cell receptor (TCR) activation. Phytochemistry, 2018, 146, 36-46.
Ren, Y.; Yu, J.; Kinghorn, A.D. Development of anticancer agents from plant-derived sesquiterpene lactones. Curr. Med. Chem., 2016, 23(23), 2397-2420.
Ollivier, A.; Grougnet, R.; Cachet, X.; Meriane, D.; Ardisson, J.; Boutefnouchet, S.; Deguin, B. Large scale purification of the SERCA inhibitor thapsigargin from Thapsia garganica L. Roots using centrifugal partition chromatography. J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 2013, 926, 16-20.
Thastrup, O.; Cullen, P.J.; Drøbak, B.K.; Hanley, M.R.; Dawson, A.P. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc. Natl. Acad. Sci. USA, 1990, 87(7), 2466-2470.
Martins, S.M.; Torres, C.R.; Ferreira, S.T. Inhibition of the ecto-ATPdiphosphohydrolase of Schistosoma mansoni by thapsigargin. Biosci. Rep., 2000, 20(5), 369-381.
Penido, M.L.O.; Resende, D.M.; Vianello, M.A.; Humberto da Silveira Bordin, F.; Jacinto, A.A.; Dias, W.D.; Montesano, M.Â.; Nelson, D.L.; Marcos Zech Coelho, P.; Vasconcelos, E.G. A new series of schistosomicide drugs, the alkylaminoalkanethiosulfuric acids, partially inhibit the activity of Schistosoma mansoni ATP diphosphohydrolase. Eur. J. Pharmacol., 2007, 570(1-3), 10-17.
Bernardes, C.F.; Meyer-Fernandes, J.R.; Basseres, D.S.; Castilho, R.F.; Vercesi, A.E. Ca2+-dependent permeabilization of the inner mitochondrial membrane by 4,4′-diisothiocyanatostilbene-2,2′- disulfonic acid (DIDS). BBA - Bioenerg., 1994, 1188(1-2), 93-100.
Bernardes, C.F.; Meyer-Fernandes, J.R.; Saad-Nehme, J.; Vannier-Santos, M.A.; Peres-Sampaio, C.E.; Vercesi, A.E. Effects of 4,4′-diisothyocyanatostilbene-2,2′-disulfonic acid on Trypanosoma cruzi proliferation and Ca2+ homeostasis. Int. J. Biochem. Cell Biol., 2000, 32(5), 519-527.
Crack, B.E.; Pollard, C.E.; Beukers, M.W.; Roberts, S.M.; Hunt, S.F.; Ingall, A.H.; McKechnie, K.C.W.; IJzerman, A.P.; Leff, P. Pharmacological and biochemical analysis of FPL 67156, a novel, selective inhibitor of ecto‐ATPase. Br. J. Pharmacol., 1995, 114(2), 475-481.
Lecka, J.; Gillerman, I.; Fausther, M.; Salem, M.; Munkonda, M.N.; Brosseau, J.P.; Cadot, C.; Martín-Satué, M.; D’Orléans-Juste, P.; Rousseau, É.; Poirier, D.; Künzli, B.; Fischer, B.; Sévigny, J. 8-BuS-ATP derivatives as specific NTPDase1 inhibitors. Br. J. Pharmacol., 2013, 169(1), 179-196.
Munkonda, M.N.; Kauffenstein, G.; Kukulski, F.; Lévesque, S.A.; Legendre, C.; Pelletier, J.; Lavoie, É.G.; Lecka, J.; Sévigny, J. Inhibition of human and mouse plasma membrane bound NTPDases by P2 receptor antagonists. Biochem. Pharmacol., 2007, 74(10), 1524-1534.
Lecka, J.; Rana, M.S.; Sévigny, J. Inhibition of vascular ectonucleotidase activities by the pro-drugs ticlopidine and clopidogrel favours platelet aggregation. Br. J. Pharmacol., 2010, 161(5), 1150-1160.
Gendron, F.P.; Benrezzak, O.; Krugh, B.W.; Kong, Q.; Weisman, G. a; Beaudoin, A.R. Purine signaling and potential new therapeutic approach: Possible outcomes of NTPDase inhibition. Curr. Drug Targets, 2002, 3(3), 229-245.
Baqi, Y.; Weyler, S.; Iqbal, J.; Zimmermann, H.; Müller, C.E. Structure-activity relationships of anthraquinone derivatives derived from bromaminic acid as inhibitors of ectonucleoside triphosphate diphosphohydrolases (E-NTPDases). Purinergic Signal., 2009, 5(1), 91-106.
Berti, S.L.; Bonan, C.D.; Da Silva, F.L.; Battastini, A.M.O.; Sarkis, J.J.F.; Wannmacher, C.M.D. Phenylalanine and phenylpyruvate inhibit ATP diphosphohydrolase from rat brain cortex. Int. J. Dev. Neurosci., 2001, 19(7), 649-653.
Borges-Pereira, L.; Meissner, K.A.; Wrenger, C.; Garcia, C.R.S. Plasmodium falciparum GFP-E-NTPDase expression at the intraerythrocytic stages and its inhibition blocks the development of the human malaria parasite. Purinergic Signal., 2017, 13(3), 267-277.
Torres, C.R.; Vasconcelos, E.G.; Ferreira, S.T.; Verjovski-Almeida, S. Divalent cation dependence and inhibition of Schistosoma mansoni ATP diphosphohydrolase by fluorosulfonylbenzoyl adenosine. Eur. J. Biochem., 1998, 251(1-2), 516-521.
Pauls, H.; Bredenbröcker, B.; Schoner, W. Inactivation of (Na++ K+)‐ATPase by Chromium(III) complexes of nucleotide triphosphates. Eur. J. Biochem., 1980, 109(2), 523-533.
Moreira, O.C.; Rios, P.F.; Esteves, F.F.; Meyer-Fernandes, J.R.; Barrabin, H. CrATP as a new inhibitor of ecto-ATPases of trypanosomatids. Parasitology, 2009, 136(1), 35-44.
Ranade, V.V. Drug delivery systems-2. site-specific drug delivery utilizing monoclonal antibodies. J. Clin. Pharmacol., 1989, 29(10), 873-884.
Maia, A.C.R.G.; Porcino, G.N.; Detoni, M.L.; Emídio, N.B.; Marconato, D.G.; De Faria Pinto, P.; Fessel, M.R.; Reis, A.B.; Juliano, L.; Juliano, M.A.; Marques, M.J.; Vasconcelos, E.G. An antigenic domain within a catalytically active Leishmania infantum nucleoside triphosphate diphosphohydrolase (NTPDase 1) is a target of inhibitory antibodies. Parasitol. Int., 2013, 62(1), 44-52.
Porcino, G.N.; Carvalho-Campos, C.; Maia, A.C.R.G.; Detoni, M.L.; De Faria Pinto, P.; Coimbra, E.S.; Marques, M.J.; Juliano, M.A.; Juliano, L.; Diniz, V.Á.; Corte-Real, S.; Vasconcelos, E.G. Leishmania (Viannia) braziliensis nucleoside triphosphate diphosphohydrolase (NTPDase 1): Localization and in vitro inhibition of promastigotes growth by polyclonal antibodies. Exp. Parasitol., 2012, 132(2), 293-299.
Grossman, C.J. Regulation of the immune system by sex steroids. Endocr. Rev., 1984, 5(3), 435-455.
Rückert, C.; Stuepp, C. dos S.; Gottardi, B.; Rosa, J.; Cisilotto, J.; Borges, F.P.; Rosemberg, D.B.; Bogo, M.R.; Tasca, T.; De Carli, G.A.; Bonan, C.D. Trichomonas vaginalis: Dehydroepiandrosterone sulfate and 17β-estradiol alter NTPDase activity and gene expression. Exp. Parasitol., 2010, 125(3), 187-195.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 16 September, 2019
Page: [873 - 884]
Pages: 12
DOI: 10.2174/1389203720666190704152827
Price: $65

Article Metrics

PDF: 24