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Activities of anti-Toxoplasma drugs and compounds against tissue cysts in the last three decades (1987 to 2017), a systematic review

  • Mahbobeh Montazeri
  • Saeed Mehrzadi
  • Mehdi Sharif
  • Shahabeddin Sarvi
  • Shayesteh Shahdin
  • Ahmad Daryani
Review
  • 61 Downloads

Abstract

Currently, there is no approved therapy that can eradicate Toxoplasma gondii tissue cysts, which are responsible for chronic infection. This systematic review was performed to assess drugs or compounds that can be used as anti-T. gondii tissue cysts in vitro and in vivo. English electronic databases (i.e., PubMed, Science Direct, Scopus, Google Scholar, and Web of Science) were systematically searched for articles published up to 2017. A total of 55 papers published from 1987 to 2017 were eligible for inclusion in this systematic review. Among the drugs, atovaquone and azithromycin were found effective after long-term inoculation into mice; however, clinical cases of resistance to these drugs have been reported. Also, FR235222, QUI-11, tanshinone IIA, and hydroxyzine were shown to be effective against Toxoplasma cysts, but their effectiveness in vivo remains unknown. Additionally, compound 32, endochin-like quinolones, miltefosine, and guanabenz can be used as effective antiparasitic with the unique ability to reduce brain tissue cysts in chronically infected mice. Importantly, these antimicrobial agents are significant criteria for drug candidates. Future studies should focus on the biology and drug susceptibility of the cyst form of T. gondii in chronic toxoplasmosis patients to find more effective strategies that have sterilizing activity for eliminating T. gondii tissue cysts from the host, preventing disease relapse and potentially shortening the required duration of drug administration.

Graphical abstract

Keywords

Toxoplasma gondii Toxoplasmosis Drugs Compounds Tissue cysts 

Notes

Acknowledgments

We would like to thank the Vice Chancellors for Research of the Mazandaran University of Medical Sciences, Sari, Iran (grant number 1430) for the financial support. We would also like to thank the Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.

Author contributions

A.D. and M.S. designed the systematic review protocol; M.M., S.S.H., and S.H.S. searched the databases for potentially eligible articles based on their titles and abstracts; M.M. and S.S.H. extracted the data; M.M. wrote the manuscript; and S.M. critically reviewed the manuscript. All the authors read and approved the final manuscript for publication.

Compliance with ethical standards

Conflict interest

The authors declare that there is no conflict of interest.

References

  1. Afifi MA, Al-Rabia MW (2015) The immunomodulatory effects of rolipram abolish drug-resistant latent phase of Toxoplasma gondii infection in a murine model. JMAU 3(2):86–91PubMedGoogle Scholar
  2. Afifi MA, Jiman-Fatani AA, Al-Rabia MW, Al-Hussainy NH (2014) Application of a phosphodiesterase-4 (PDE4) inhibitor to abort chronic toxoplasmosis and to mitigate consequential pathological changes. JMAU 2(2):94–99Google Scholar
  3. Alqaisi A, Mbekeani A, Llorens MB, Elhammer A, Denny P (2017) The antifungal Aureobasidin A and an analogue are active against the protozoan parasite Toxoplasma gondii but do not inhibit sphingolipid biosynthesis. Parasitology 1–8Google Scholar
  4. Araujo F, Huskinson-Mark J, Gutteridge W, Remington J (1992a) In vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against the cyst form of Toxoplasma gondii. Antimicrob Agents Chemother 36(2):326–330CrossRefPubMedPubMedCentralGoogle Scholar
  5. Araujo F, Huskinson J, Remington J (1991) Remarkable in vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii. Antimicrob Agents Chemother 35(2):293–299CrossRefPubMedPubMedCentralGoogle Scholar
  6. Araujo F, Prokocimer P, Lin T, Remington J (1992b) Activity of clarithromycin alone or in combination with other drugs for treatment of murine toxoplasmosis. Antimicrob Agents Chemother 36(11):2454–2457CrossRefPubMedPubMedCentralGoogle Scholar
  7. Araujo F, Slifer T, Remington J (1994) Rifabutin is active in murine models of toxoplasmosis. Antimicrob Agents Chemother 38(3):570–575CrossRefPubMedPubMedCentralGoogle Scholar
  8. Araujo FG, Khan AA, Remington JS (1996) Rifapentine is active in vitro and in vivo against Toxoplasma gondii. Antimicrob Agents Chemother 40(6):1335–1337PubMedPubMedCentralGoogle Scholar
  9. Araujo FG, Khan AA, Slifer TL, Bryskier A, Remington JS (1997) The ketolide antibiotics HMR 3647 and HMR 3004 are active against Toxoplasma gondii in vitro and in murine models of infection. Antimicrob Agents Chemother 41(10):2137–2140PubMedPubMedCentralGoogle Scholar
  10. Araujo FG, Slifer T (1995) Nonionic block copolymers potentiate activities of drugs for treatment of infections with Toxoplasma gondii. Antimicrob Agents Chemother 39(12):2696–2701CrossRefPubMedPubMedCentralGoogle Scholar
  11. Baatz H, Mirshahi A, Puchta J, Gümbel H, Hattenbach L-O (2006) Reactivation of toxoplasma retinochoroiditis under atovaquone therapy in an immunocompetent patient. Ocul Immunol Inflamm 14(3):185–187CrossRefPubMedGoogle Scholar
  12. Benmerzouga I, Checkley LA, Ferdig MT, Arrizabalaga G, Wek RC, Sullivan WJ (2015) Guanabenz repurposed as an antiparasitic with activity against acute and latent toxoplasmosis. Antimicrob Agents Chemother 59(11):6939–6945CrossRefPubMedPubMedCentralGoogle Scholar
  13. Bottari NB, Baldissera MD, Tonin AA, Rech VC, Alves CB, D'Avila F, Thomé GR, Guarda NS, Moresco RN, Camillo G, Vogel FF, Luchese C, Schetinger MRC, Morsch VM, Tochetto C, Fighera R, Nishihira VSK, da Silva AS (2016) Synergistic effects of resveratrol (free and inclusion complex) and sulfamethoxazole-trimetropim treatment on pathology, oxidant/antioxidant status and behavior of mice infected with Toxoplasma gondii. Microb Pathog 95:166–174CrossRefPubMedGoogle Scholar
  14. Bougdour A, Maubon D, Baldacci P, Ortet P, Bastien O, Bouillon A, Barale JC, Pelloux H, Ménard R, Hakimi MA (2009) Drug inhibition of HDAC3 and epigenetic control of differentiation in Apicomplexa parasites. J Exp Med 206(4):953–966CrossRefPubMedPubMedCentralGoogle Scholar
  15. Braga-Silva CF, Suhett CSR, Drozino RN, Moreira NM, Sant’Ana DMG, de Araújo SM (2016) Biotherapic of Toxoplasma gondii reduces parasite load, improves experimental infection, protects myenteric neurons and modulates the immune response in mice with toxoplasmosis. Eur J Integr Med 8(5):865–874CrossRefGoogle Scholar
  16. Buchholz KR, Bowyer PW, Boothroyd JC (2013) Bradyzoite pseudokinase 1 is crucial for efficient oral infectivity of the Toxoplasma gondii tissue cyst. Eukaryot Cell 12(3):399–410CrossRefPubMedPubMedCentralGoogle Scholar
  17. Chang HR, Arsenijevic D, Comte R, Polak A, Then RL, Pechere J-C (1994) Activity of epiroprim (Ro 11-8958), a dihydrofolate reductase inhibitor, alone and in combination with dapsone against Toxoplasma gondii. Antimicrob Agents Chemother 38(8):1803–1807CrossRefPubMedPubMedCentralGoogle Scholar
  18. Chang HR, Comte R, Piguet P-F, Pechère J-C (1991) Activity of minocycline against Toxoplasma gondii infection in mice. J Antimicrob Chemother 27(5):639–645CrossRefPubMedGoogle Scholar
  19. Chew WK, Segarra I, Ambu S, Mak JW (2012) Significant reduction of brain cysts caused by Toxoplasma gondii after treatment with spiramycin coadministered with metronidazole in a mouse model of chronic toxoplasmosis. Antimicrob Agents Chemother 56(4):1762–1768CrossRefPubMedPubMedCentralGoogle Scholar
  20. Chirgwin K, Hafner R, Leport C, Remington J, Andersen J, Bosler EM, Roque C, Rajicic N, McAuliffe V, Morlat P, Jayaweera DT, Vilde JL, Luft BJ, the AIDS Clinical Trials Group 237/Agence Nationale de Recherche sur le SIDA, Essai 039 Study Team (2002) Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 study. Clin Infect Dis 34(9):1243–1250CrossRefPubMedGoogle Scholar
  21. Choi W-Y, Park S-K, Nam H-W, Kim D-J (1994) Culture of tissue-cyst forming strain of Toxoplasma gondii and the effect of cyclic AMP and pyrimidine salvage inhibitors. Korean J Parasitol 32(1):19–26CrossRefPubMedGoogle Scholar
  22. Couzinet S, Dubremetz J, Buzoni-Gatel D, Jeminet G, Prensier G (2000) In vitro activity of the polyether ionophorous antibiotic monensin against the cyst form of Toxoplasma gondii. Parasitology 121(4):359–365CrossRefPubMedGoogle Scholar
  23. De Lima LPO, Seabra SH, Carneiro H, Barbosa HS (2015) Effect of 3-bromopyruvate and atovaquone on infection during in vitro interaction of Toxoplasma gondii and LLC-MK2 cells. Antimicrob Agents Chemother 59(9):5239–5249CrossRefPubMedPubMedCentralGoogle Scholar
  24. Djurković-Djaković O, Milenković V, Nikolić A, Bobić B, Grujić J (2002) Efficacy of atovaquone combined with clindamycin against murine infection with a cystogenic (Me49) strain of Toxoplasma gondii. J Antimicrob Chemother 50(6):981–987CrossRefPubMedGoogle Scholar
  25. Doggett JS, Nilsen A, Forquer I, Wegmann KW, Jones-Brando L, Yolken RH, Bordon C, Charman SA, Katneni K, Schultz T, Burrows JN, Hinrichs DJ, Meunier B, Carruthers VB, Riscoe MK (2012) Endochin-like quinolones are highly efficacious against acute and latent experimental toxoplasmosis. Proc Natl Acad Sci 109(39):15936–15941CrossRefPubMedGoogle Scholar
  26. Doleski PH, Leal DBR, Machado VS, Bottari NB, Manzoni AG, Casali EA, Moritz CEJ, Rocha ACA, Camillo G, Vogel FF, Stefani LM, Mendes RE, da Silva AS (2017a) Diphenyl diselenide modulates nucleotidases, reducing inflammatory responses in the liver of Toxoplasma gondii-infected mice. Purinergic Signal 13(4):489–496CrossRefPubMedPubMedCentralGoogle Scholar
  27. Doleski PH, ten Caten MV, Passos DF, Castilhos LG, Leal DBR, Machado VS, Bottari NB, Vogel FF, Mendes RE, da Silva AS (2017b) Toxoplasmosis treatment with diphenyl diselenide in infected mice modulates the activity of purinergic enzymes and reduces inflammation in spleen. Exp Parasitol 181:7–13CrossRefPubMedGoogle Scholar
  28. Dubey J (1977) Toxoplasma, Hammondia, Besnoitia, Sarcocystis, and other tissue cyst-forming coccidia of man and animals. Parasitic Protozoa 3:101–237Google Scholar
  29. Dubey J (1988) Long-term persistence of Toxoplasma gondii in tissues of pigs inoculated with T gondii oocysts and effect of freezing on viability of tissue cysts in pork. Am J Vet Res 49(6):910–913PubMedGoogle Scholar
  30. Dubey J, Jones J (2008) Toxoplasma gondii infection in humans and animals in the United States. Int J Parasitol 38(11):1257–1278CrossRefPubMedGoogle Scholar
  31. Dubey J, Lindsay D, Speer C (1998) Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts. Clin Microbiol Rev 11(2):267–299PubMedPubMedCentralGoogle Scholar
  32. Dumas J-L, Chang R, Mermillod B, Piguet PF, Comte R, Pechère J-C (1994) Evaluation of the efficacy of prolonged administration of azithromycin in a murine model of chronic toxoplasmosis. J Antimicrob Chemother 34(1):111–118CrossRefPubMedGoogle Scholar
  33. Dumas J-L, Pizzolato G, Pechère J-C (1999) Evaluation of trimethoprim and sulphamethoxazole as monotherapy or in combination in the management of toxoplasmosis in murine models. Int J Antimicrob Agents 13(1):35–39CrossRefPubMedGoogle Scholar
  34. Eissa MM, Barakat AM, Amer EI, Younis LK (2015) Could miltefosine be used as a therapy for toxoplasmosis? Exp Parasitol 157:12–22CrossRefPubMedGoogle Scholar
  35. El-Sayed NM, Ismail KA, Badawy AF, Elhasanein KF (2016) In vivo effect of anti-TNF agent (etanercept) in reactivation of latent toxoplasmosis. J Parasit Dis 40(4):1459–1465CrossRefPubMedGoogle Scholar
  36. El-Zawawy LA, El-Said D, Mossallam SF, Ramadan HS, Younis SS (2015) Preventive prospective of triclosan and triclosan-liposomal nanoparticles against experimental infection with a cystogenic ME49 strain of Toxoplasma gondii. Acta Trop 141:103–111CrossRefPubMedGoogle Scholar
  37. Elfadaly HA, Hassanain MA, Shaapan RM, Hassanain NA, Barakat AM (2015) Corticosteroids opportunist higher Toxoplasma gondii brain cysts in latent infected mice. Int J Zool Res 11(4):169–176CrossRefGoogle Scholar
  38. Ferguson D, Huskinson-Mark J, Araujo F, Remington J (1994) An ultrastructural study of the effect of treatment with atovaquone in brains of mice chronically infected with the ME49 strain of Toxoplasma gondii. Int J Clin Exp Pathol 75(2):111Google Scholar
  39. Ferreira R, Oliveira A, Gualberto S, Vitor R (2002) Activity of natural and synthetic naphthoquinones against Toxoplasma gondii, in vitro and in murine models of infection. Parasite 9(3):261–269CrossRefPubMedGoogle Scholar
  40. Ferreira RA, de Oliveira AB, Gualberto SA, Miguel del Corral JM, Fujiwara RT, Gazzinelli Guimarães PH, de Almeida Vitor RW (2012) New naphthoquinones and an alkaloid with in vitro activity against Toxoplasma gondii RH and EGS strains. Exp Parasitol 132(4):450–457CrossRefPubMedGoogle Scholar
  41. Ferreira RA, Oliveira AB, Ribeiro MF, Tafuri WL, Vitor RW (2006) Toxoplasma gondii: in vitro and in vivo activities of the hydroxynaphthoquinone 2-hydroxy-3-(1′-propen-3-phenyl)-1, 4-naphthoquinone alone or combined with sulfadiazine. Exp Parasitol 113(2):125–129CrossRefPubMedGoogle Scholar
  42. Fuentes-Castro BE, Reyes-García JG, Valenzuela-Vargas MT, Martínez-Gómez F (2017) Histopathology of murine toxoplasmosis under treatment with dialyzable leukocyte extract. Mem Inst Oswaldo Cruz 112(11):741–747CrossRefPubMedPubMedCentralGoogle Scholar
  43. Goodwin DG, Strobl J, Mitchell SM, Zajac AM, Lindsay DS (2008) Evaluation of the mood-stabilizing agent valproic acid as a preventative for toxoplasmosis in mice and activity against tissue cysts in mice. J Parasitol 94(2):555–557CrossRefPubMedGoogle Scholar
  44. Gormley PD, Pavesio CE, Minnasian D, Lightman S (1998) Effects of drug therapy on Toxoplasma cysts in an animal model of acute and chronic disease. Invest Ophthalmol Vis Sci 39(7):1171–1175PubMedGoogle Scholar
  45. Havelaar AH, Haagsma JA, Mangen MJJ, Kemmeren JM, Verhoef LPB, Vijgen SMC, Wilson M, Friesema IHM, Kortbeek LM, van Duynhoven YTHP, van Pelt W (2012) Disease burden of foodborne pathogens in the Netherlands, 2009. Int J Food Microbiol 156(3):231–238CrossRefPubMedGoogle Scholar
  46. Hofflin JM, Remington JS (1987) Clindamycin in a murine model of toxoplasmic encephalitis. Antimicrob Agents Chemother 31(4):492–496CrossRefPubMedPubMedCentralGoogle Scholar
  47. Huskinson-Mark J, Araujo FG, Remington JS (1991) Evaluation of the effect of drugs on the cyst form of Toxoplasma gondii. J Infect Dis 164(1):170–177CrossRefPubMedGoogle Scholar
  48. Konrad C, Queener SF, Wek RC, Sullivan WJ (2013) Inhibitors of eIF2α dephosphorylation slow replication and stabilize latency in Toxoplasma gondii. Antimicrob Agents Chemother 57(4):1815–1822CrossRefPubMedPubMedCentralGoogle Scholar
  49. Kul O, Yildiz K, Ocal N, Freyre A, Deniz A, Karahan S, Atmaca HT, Gokpinar S, Dincel GC, Uzunalioğlu T, Terzi OS (2013) In-vivo efficacy of toltrazuril on experimentally induced Toxoplasma gondii tissue cysts in lambs: a novel strategy for prevention of human exposure to meat-borne toxoplasmosis. Res Vet Sci 94(2):269–276CrossRefPubMedGoogle Scholar
  50. Lourido S, Zhang C, Lopez MS, Tang K, Barks J, Wang Q, Wildman SA, Shokat KM, Sibley LD (2013) Optimizing small molecule inhibitors of calcium-dependent protein kinase 1 to prevent infection by Toxoplasma gondii. J Med Chem 56(7):3068–3077CrossRefPubMedPubMedCentralGoogle Scholar
  51. Luft BJ, Remington JS (1992) Toxoplasmic encephalitis in AIDS. Clin Infect Dis 15(2):211–222CrossRefPubMedGoogle Scholar
  52. Machado VS, Bottari NB, Baldissera MD, Isabel de Azevedo M, Rech VC, Ianiski FR, Vaucher RA, Mendes RE, Camillo G, Vogel FF, de la Rue ML, Carmo GM, Tonin AA, da Silva AS (2016) Toxoplasma gondii: effects of diphenyl diselenide in experimental toxoplasmosis on biomarkers of cardiac function. Exp Parasitol 167:25–31CrossRefPubMedGoogle Scholar
  53. Mahmoud DM, Mahmoud MS, Ezz-El-Din HM, Abo-Zahra FA, Meselhey RA (2017) Artesunate effect on RH virulent and ME49 non-virulent strains of Toxoplasma gondii: in vitro and in vivo experimental studies. Sci Parasitol 17:83–92Google Scholar
  54. Martins-Duarte ÉS, Lemgruber L, de Souza W, Vommaro RC (2010) Toxoplasma gondii: fluconazole and itraconazole activity against toxoplasmosis in a murine model. Exp Parasitol 124(4):466–469CrossRefPubMedGoogle Scholar
  55. Maubon D, Bougdour A, Wong YS, Brenier-Pinchart MP, Curt A, Hakimi MA, Pelloux H (2010) Activity of the histone deacetylase inhibitor FR235222 on Toxoplasma gondii: inhibition of stage conversion of the parasite cyst form and study of new derivative compounds. Antimicrob Agents Chemother 54(11):4843–4850CrossRefPubMedPubMedCentralGoogle Scholar
  56. Meacham RH et al (1980) Relationship of guanabenz concentrations in brain and plasma to antihypertensive effect in the spontaneously hypertensive rat. J Pharmacol Exp Ther 214(3):594–598PubMedGoogle Scholar
  57. Megged O, Shalit I, Yaniv I, Stein J, Fisher S, Levy I (2008) Breakthrough cerebral toxoplasmosis in a patient receiving atovaquone prophylaxis after a hematopoietic stem cell transplantation. Pediatr Transplant 12(8):902–905CrossRefPubMedGoogle Scholar
  58. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269CrossRefPubMedGoogle Scholar
  59. Mokua Mose J et al (2017) Development of neurological mouse model for toxoplasmosis using Toxoplasma gondii isolated from chicken in Kenya Patholog Res Int 2017Google Scholar
  60. Montazeri M, Ebrahimzadeh MA, Ahmadpour E, Sharif M, Sarvi S, Daryani A (2016) Evaluation of propranolol effect on experimental acute and chronic toxoplasmosis using quantitative PCR. Antimicrob Agents Chemother 60(12):7128–7133PubMedPubMedCentralGoogle Scholar
  61. Montazeri M, Sharif M, Sarvi S, Mehrzadi S, Ahmadpour E, Daryani A (2017) A systematic review of in vitro and in vivo activities of anti-Toxoplasma drugs and compounds (2006–2016). Front Microbiol 8:25PubMedPubMedCentralGoogle Scholar
  62. Murata Y, Sugi T, Weiss LM, Kato K (2017) Identification of compounds that suppress Toxoplasma gondii tachyzoites and bradyzoites. PLoS One 12(6):e0178203CrossRefPubMedPubMedCentralGoogle Scholar
  63. Rutaganira FU, Barks J, Dhason MS, Wang Q, Lopez MS, Long S, Radke JB, Jones NG, Maddirala AR, Janetka JW, el Bakkouri M, Hui R, Shokat KM, Sibley LD (2017) Inhibition of calcium dependent protein kinase 1 (CDPK1) by pyrazolopyrimidine analogs decreases establishment and reoccurrence of central nervous system disease by Toxoplasma gondii. J Med Chem 60(24):9976–9989CrossRefPubMedGoogle Scholar
  64. Saraei M, Ghaderi Y, Mosavi T, Shahnazi M, Nassiri-Asl M, Jahanihashemi H (2016) The effect of fluphenazine and thioridazine on Toxoplasma gondii in vivo. Iran J Parasitol 11(2):226PubMedPubMedCentralGoogle Scholar
  65. Saraei M, Samadzadeh N, Khoeini J, Shahnazi M, Nassiri-Asl M, Jahanihashemi H (2015) In vivo anti-Toxoplasma activity of aripiprazole. Iran J Basic Med Sci 18(9):938PubMedPubMedCentralGoogle Scholar
  66. Sarciron M-E, Lawton P, Saccharin C, Petavy A-F, Peyron F (1997) Effects of 2′, 3′-dideoxyinosine on Toxoplasma gondii cysts in mice. Antimicrob Agents Chemother 41(7):1531–1536PubMedPubMedCentralGoogle Scholar
  67. Sarciron M, Walchshofer N, Paris J, Petavy A, Peyron F (1998) Phenylalanine derivatives active against Toxoplasma gondii brain cysts in mice. Parasite 5(4):359–364CrossRefPubMedGoogle Scholar
  68. Scallan E et al (2011) Foodborne illness acquired in the United States—major pathogens. Emerg Infect Dis 17(1)Google Scholar
  69. Shu H, Jiang L (2002) Effect of garlicin and minocycline on the cyst formation of Toxoplasma gondii in mice. Chinese Journal of Zoonoses 18(1):100–101Google Scholar
  70. Sordet F, Aumjaud Y, Fessi H, Derouin F (1998) Assessment of the activity of atovaquone-loaded nanocapsules in the treatment of acute and chronic murine toxoplasmosis. Parasite 5(3):223–229CrossRefPubMedGoogle Scholar
  71. Sumyuen MH, Garin YJF, Derouin F (1996) Effect of immunosuppressive drug regimens on acute and chronic murine toxoplasmosis. J Parasitol Res 82(8):681–686CrossRefGoogle Scholar
  72. Surolia N, Surolia A (2001) Triclosan offers protection against blood stages of malaria by inhibiting enoyl-ACP reductase of Plasmodium falciparum. Nat Med 7(2):167–173CrossRefPubMedGoogle Scholar
  73. Tawfeek G, Oteifa N, Mustafa M (2001) Prophylactic efficacy of recombinant IL-12, clindamycin alone or in combination against experimental reactivated toxoplasmosis. J Egypt Soc Parasitol 31(3):853–866PubMedGoogle Scholar
  74. Vidadala RSR, Rivas KL, Ojo KK, Hulverson MA, Zambriski JA, Bruzual I, Schultz TL, Huang W, Zhang Z, Scheele S, DeRocher AE, Choi R, Barrett LK, Siddaramaiah LK, Hol WGJ, Fan E, Merritt EA, Parsons M, Freiberg G, Marsh K, Kempf DJ, Carruthers VB, Isoherranen N, Doggett JS, van Voorhis WC, Maly DJ (2016) Development of an orally available and central nervous system (CNS) penetrant Toxoplasma gondii calcium-dependent protein kinase 1 (Tg CDPK1) inhibitor with minimal human ether-a-go-go-related gene (hERG) activity for the treatment of toxoplasmosis. J Med Chem 59(13):6531–6546CrossRefPubMedPubMedCentralGoogle Scholar
  75. Weiss LM, Kim K (2000) The development and biology of bradyzoites of Toxoplasma gondii. Front Biosci 5:D391–d405CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Mahbobeh Montazeri
    • 1
    • 2
  • Saeed Mehrzadi
    • 3
  • Mehdi Sharif
    • 1
    • 4
  • Shahabeddin Sarvi
    • 1
    • 5
  • Shayesteh Shahdin
    • 1
  • Ahmad Daryani
    • 1
    • 5
  1. 1.Toxoplasmosis Research CenterMazandaran University of Medical SciencesSariIran
  2. 2.Student Research CommitteeMazandaran University of Medical SciencesSariIran
  3. 3.Razi Drug Research CenterIran University of Medical SciencesTehranIran
  4. 4.Department of Parasitology, School of Medicine, Sari BranchIslamic AZAD UniversitySariIran
  5. 5.Department of Parasitology and Mycology, Sari Medical SchoolMazandaran University of Medical SciencesSariIran

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