Iranian Journal of Parasitology 2015. 10(2):171-180.

Anti-Toxoplasma Activity of 2-(Naphthalene-2-γlthiol)-1H Indole.
Qasem Asgari, Hossein Keshavarz, Mostafa Rezaeian, Hossein Sadeghpour, Ramin Miri, Mohammad Hossein Motazedian

Abstract


Background:This study was undertaken to evaluate the viability, infectivity and immunity of Toxoplasma gondii tachyzoites exposed to 2-(naphthalene-2-ylthio)-1H-indole.
 Methods:Tachyzoites of RH strain were incubated in various concentrations of 2- (naphthalene-2-ylthio)-1H-indole (25-800μM) for 1.5 hours. Then, they were stained by PI and analyzed by Fluorescence-activated cell sorting (FACS). To eval-uate the infectivity, the tachyzoites exposed to the different concentrations of the compound were inoculated to 10 BALB/c mice groups. For Control, parasites ex-posed to DMSO (0.2% v/v) were also intraperitoneally inoculated into two groups of mice. The immunity of the exposed tachyzoites was evaluated by inoculation of the naïve parasite to the survived mice.
Results:The LD50 of 2-(naphthalene-2-ylthio)-1H-indole was 57 μmol. The lon-gevity of mice was dose dependent. Five mice out of group 400μmol and 3 out of group 800μmol showed immunization to the parasite.
 Conclusion:Our findings demonstrated the toxoplasmocidal activity of the com-pound. The presence of a well-organized transporter mechanism for indole com-pounds within the parasite in conjunction with several effective mechanisms of these compounds on Toxoplasma viability would open a window for production of new drugs and vaccines.


Keywords


2-(naphthalene-2-ylthio)-1H-indole; Immunity; Infectivity; Toxoplasma gondii; Viability

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References


Dubey JP. History of the discovery of the life cycle of Toxoplasma gondii. Int J Parasitol.2009; 39: 877-882.

Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004; 363: 1965-1976.

Remington JS, Mcleod R, Thulliez P. In Infection Diseases of the Fetus and Newborn Infant ed. Philadelphia: Elsevier Saunders; 2006.

Joynson DHM, Wreghitt TG. In Toxoplasmosis: A comprehensive clinical guide, ed. Cambridge: Cambridge University Press; 2001.

Oksenhendler E, Charreau I, Tournerie C, Azihary M, Carbon C, Aboulker JP. Toxoplasma gondii infection in advanced HIV infection. AIDS.1994; 8: 483-487.

Pereira-Chioccola VL, Vidal JE, Su C. Toxoplasma gondii infection and cerebral toxoplasmosis in HIV-infected patients. Future Microbiol. 2009; 4: 1363-1379.

Anderson AC. Targeting DHFR in parasitic protozoa. Drug Discov Today.2005; 10: 121-128.

Mori T, Kato J, and Okamoto S. Pancytope-nia due to pyrimethamine triggered by trans-plant-associated microangiopathy after alloge-neic bone marrow transplantation. J Infect Chem. 2011; 17(6): 866–867.

Lipka B, Milewska-Bobula B, Filipek M. Monitoring of plasma concentration of pyrimethamine (PYR) in infants with

Iran J Parasitol: Vol. 10, No. 2, Apr -Jun 2015, pp.171-180

Available at: http://ijpa.tums.ac.ir

congenital Toxoplasma gondii infection own observations. Wiad Parazytol.2011; 57: 87-92.

Ostlere LS, Langtry JA, Staughton RC. Allergy to spiramycin during prophylactic treatment of fetal toxoplasmosis. Br Med J.1991; 302: 970.

Rubinstein E, Keller N. Spiramycin renaissance. J Antimicrob Chemother.1998; 42: 572-576.

Grujic J, Djurkovic-Djakovic O, Nikolic A, Klun I, Bobic B. Effectiveness of spiramycin in murine models of acute and chronic tox-oplasmosis. Int J Antimicrob Agents. 2005; 25: 226-230.

Dai W, Pan H, Kwok O, Dubey JP. Human indoleamine 2, 3-dioxygenase inhibits Toxoplasma gondii growth in fibroblast cells. J Interferon Res.1994; 14: 313-317.

Pfefferkorn ER, Eckel M, Rebhun S. Interferon-gamma suppresses the growth of Toxoplasma gondii in human fibroblasts through starvation for tryptophan. Mol Biochem Parasitol. 2019; 86: 215-224.

Asai T, Takeuchi T, Diffenderfer J, Sibley LD. Identification of small-molecule inhibitors of nucleoside triphosphate hydrolase in Toxoplasma gondii. Antimicrob Agents Chemother. 2002; 46: 2393-2399.

Kirihara a, Asai Y, Ogawa S, Noguchi T, Hatano A, Hiraib Y. A Mild and Environmentally Benign Oxidation of Thiols to Disulfides. Synthesis.2007; 21: 3286-3289.

Hamel P, Zajac N, Atkinson JG, Girard Y. Nonreductive Desulfenylation of 3-Indolyl Sulfides. Improved Syntheses of 2-Substituted Indoles and 2-Indolyl Sulfides. J Organ Chem. 1994; 59: 6372-6377.

Akins CK, Panicker S, Cunningham CL.In Laboratory Animals in Research and Teaching: Ethics, Care, and Methods. Washington, DC: APA; 2004.

Asgari Q, Keshavarz H, Rezaeian M, Motazedian MH, Shojaee S, Mohebali M,Miri M. Direct Effect of Two Naphthalene-Sul-fonyl-Indole Compounds on Toxoplasma gondii-Tachyzoite. J Parasitol Res. 2013; 2013: 1-8.

Di Cristina M, Marocco D, Galizi R, Proietti C, Spaccapelo R, Crisanti A. Temporal and spatial distribution of Toxoplasma gondii differentiation into Bradyzoites and tissue cyst formation in vivo. Infect Immun. 2008; 76: 3491-3501.

Suzuki M, Maghni K, Molet S, Shimbara A, Hamid QA, Martin JG. IFN-gamma secretion by CD8T cells inhibits allergen-induced airway eosinophilia but not late airway responses. J Allergy Clin Immunol. 2002; 109: 803-809.

Seymour RL, Ganapathy V, Mellor AL, Munn DH. A high-affinity, tryptophan-selective amino acid transport system in human macrophages. J Leukocyte Biol. 2006; 80: 1320-1327.

Schwab JC, Beckers CJ, Joiner KA. The parasitophorous vacuole membrane surround-ing intracellular Toxoplasma gondii functions as a molecular sieve. Proc Natl Acad Sci U S A.1994; 91: 509-513.

Schwartzman JD, Pfefferkorn ER. Toxoplasma gondii: purine synthesis and salvage in mutant host cells and parasites. Exp Parasitol. 1982; 53: 77-86.

Sibley LD, Niesman IR, Asai T, Takeuchi T. Toxoplasma gondii: secretion of a potent nucleoside triphosphate hydrolase into the parasitophorous vacuole. Exp Parasitol. 1994; 79: 301-311.

Nakaar V, Samuel BU, Ngo EO, Joiner KA. Targeted reduction of nucleoside triphosphate hydrolase by antisense RNA inhibits Toxoplasma gondii proliferation. J Biol Chem. 1999; 274: 5083-5087.

Browne LM, Conn KL, Ayer WA, Tewari JP. The camalexins: new phytoalexins produced in the leaves of Camelina sativa (Cruciferae). Tetrehedron. 1991; 47: 3909-3914.

Tsuji J, Jackson EP, Gage DA, Hammerschmidt R, Somerville SC. Phytoalexin Accumulation in Arabidopsis thaliana during the Hypersensitive Reaction to Pseudomonas syringae pv syringae. Plant Physiol. 1992; 98: 1304-1309.

Thomma BHJ, Nelissen I, Eggermont K, Broekaert WF. Deficiency in phytoalexin production causes enhanced susceptibility of Arabidopsis thaliana to the fungus Alternaria brassicicola. Plant J. 1999; 19: 163-171.

Glawischnig E. Camalexin. Phytochemistry. 2007; 68: 401-406.

Sellam A, Dongo A, Guillemette T, Hudhomme P, Simoneau P. Transcriptional responses to exposure to the Brassica ceous defence metabolites camalexin and allyl-isothiocyanate in the necrotrophic fungus

Asgari et al.:Anti-Toxoplasma Activity of 2-(Naphthalene-2-Ylthiol)-…

Available at: http://ijpa.tums.ac.ir 180

Alternaria brassicicola. Mol Plant Pathol. 2007; 8: 195-208.

Seefeld MA, Miller WH, Newlander KA, Burgess WJ, DeWolf WE, et al. Indole naphthyridinones as inhibitors of bacterial enoyl-ACP reductases FabI and FabK. J Medicin Chem. 2003; 46: 1627-1635.

Smith MA, Moon H, Chowrira G, Kunst L. Heterologous expression of a fatty acid hydroxylase gene in developing seeds of Arabidopsis thaliana. Planta. 2003; 217: 507-516.

Mazumdar J, EH W, Masek K, CA H, Striepen B. Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival in Toxoplasma gondii. Proc Natl Acad Sci USA. 2006;103:13192-13197.

Jongert E, Roberts CW, Gargano N, Forster-Waldl E, Petersen E. Vaccines against Toxoplasma gondii: challenges and opportunities. Mem Inst Oswaldo Cruz. 2009; 104: 252-266.

Eissa MM, El-Azzouni MZ, Mady RF, Fathy FM, Baddour NM. Initial characterization of

an autoclaved Toxoplasma vaccine in mice. Exp Parasitol. 2012; 131: 310-316.

Wilkins MF, O'Connell E, Te Punga WA. Toxoplasmosis in sheep: Effect of a killed vaccine on lambing losses caused by experimental challenge with Toxoplasma gondii. N Z Vet J. 1987; 35: 31-34.

Moire N, Dion S, Lebrun M, Dubremetz JF, Dimier-Poisson I. Mic1-3KO tachyzoite a live attenuated vaccine candidate against toxoplasmosis derived from a type I strain shows features of type II strain. Exp Parasitol. 2009; 123: 111-117.

Cerede O, Dubremetz JF, Soete M, Deslee D, Vial H, et al. Synergistic role of micronemal proteins in Toxoplasma gondii virulence. J Exp Med. 2005; 201: 453-463.

Lecoeur H. Nuclear apoptosis detection by flow cytometry: influence of endogenous endonucleases. Exp Cell Res. 2002; 277: 1-14.


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