Anti-toxoplasma gondii effect of metalocomplex compounds N0414 and N5814 / Efeito anti-toxoplasma gondii do composto metalocomplexo N0414 e N5814
DOI:
https://doi.org/10.34117/bjdv7n2-330Keywords:
Toxoplasma gondii, toxoplasmosis, metallocomplexes, chemotherapy.Abstract
Toxoplasma gondii, toxoplasmosis agent, is a obligate intracellular protozoan that is able of infecting a broad spectrum of vertebrate’s cells. Toxoplasmosis is a pathology related to severe damages to immunocompromised hosts and its current chemotherapy is quite restricted, being more used the combination of sulfadiazine and pyrimethamine, which is a therapy associated with adverse reactions. This fact highlights the importance of the study of new drugs against Toxoplasma gondii. Has been studied the biological effect of new metallocomplexe compounds, which are inorganic compounds that present promising biological activity as fungicide, bactericide and antiviral. The metallocomplexes, dinuclear ferric compounds N0414 (Fe alfanaftol BMPA) and N5814 (Fe beta-naphthol BMPA) showed activity against Toxoplasma gondii in vitro and it was nontoxic to LLC-MK2 cells, being able to reduce the activity of crucial antioxidant enzymes for the defense of the parasite. In this project, it will be investigated the activities of compounds of the metallocomplexes family as the compounds coordinated to sulfadiazine as the nucleus compound of ferric N0414 and N5814, which showed anti-Toxoplasma gondii activities and were able to eliminate the infection in almost all host cells. In further steps, we will investigate what kind of death the parasite undergoes after the treatment with the compounds through the ultrastructure analysis and the usage of specific markers by fluorescence microscopy. The compounds will also be used in vivo tests with mouse models in the acute phase of toxoplasmosis to prove the efficacy of these compounds.
References
CABALLERO, Ana B. et al. In vitro and in vivo antiparasital activity against Trypanosoma cruzi of three novel 5-methyl-1, 2, 4-triazolo [1, 5-a] pyrimidin-7 (4H)-one-based complexes. Journal of inorganic biochemistry, v. 105, n. 6, p. 770-776, 2011.
DE CARVALHO, Gabriella Oliveira Alves Moreira et al. Morphological evaluation of macrophage infected with Toxoplasma Gondii. Brazilian Journal of Development, v. 7, n. 1, p. 4035-4050, 2021.
Dijrkovic-Djakovic, O., Milenkovic, V., Nikolic, A., Bobic, B., Grujic, J. Efficacy of atovaquone combined with clindamycin against murine infection with cystogenic (Me49) strain of Toxoplasma gondii. J Antimicrob Chemother. v. 50, p. 981-987, 2002.
DUBEY, J. P.; LINDSAY, D. S.; SPEER, C. A. Structures of Toxoplasma gondiitachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts. Clinical microbiology reviews, v. 11, n. 2, p. 267-299, 1998.
FERGUSON, D. J. P.; HUTCHISON, W. M.; PETTERSEN, E. Tissue cyst rupture in mice chronically infected with Toxoplasma gondii. Parasitology research, v. 75, n. 8, p. 599-603, 1989.
FERNANDES, Christiane et al. Synthesis, crystal structure, nuclease and in vitro antitumor activities of a new mononuclear copper (II) complex containing a tripodal N3O ligand. Inorganica chimica acta, v. 359, n. 10, p. 3167-3176, 2006.
Georgiev, V.S. Management of toxoplasmosis. Drugs, 48, p. 179-188, 1994.
Goulart, V., Resende, R. R. Toxoplasmose: A culpa é dos gatos? Nanocell News, 14, 2, 2015.
HAVERKOS, Harry W. Assessment of therapy for toxoplasma encephalitis: the TE study group. The American journal of medicine, v. 82, n. 5, p. 907-914, 1987.
HILL, Dolores E.; CHIRUKANDOTH, Sreekumar; DUBEY, Jitender P. Biology and epidemiology of Toxoplasma gondii in man and animals. Animal health research reviews, v. 6, n. 1, p. 41, 2005.
HORN JR, Adolfo et al. An iron-based cytosolic catalase and superoxide dismutase mimic complex. Inorganic chemistry, v. 49, n. 4, p. 1274-1276, 2010.
HORN JR, Adolfo et al. Highly efficient synthetic iron-dependent nucleases activate both intrinsic and extrinsic apoptotic death pathways in leukemia cancer cells. Journal of inorganic biochemistry, v. 128, p. 38-47, 2013.
KAMERKAR, Sushrut; DAVIS, Paul H. Toxoplasma on the brain: understanding host-pathogen interactions in chronic CNS infection. Journal of Parasitology Research, v. 2012, 2012.
KATLAMA, Christine et al. Pyrimethamine-clindamycin vs. pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS. Clinical infectious diseases, v. 22, n. 2, p. 268-275, 1996.
LEPORT, Catherine et al. Treatment of central nervous system toxoplasmosis with pyrimethamine/sulfadiazine combination in 35 patients with the acquired immunodeficiency syndrome: efficacy of long-term continuous therapy. The American journal of medicine, v. 84, n. 1, p. 94-100, 1988.
LEVINE, N. D. et al. A Newly Revised Classification of the Protozoa* THE COMMITTEE ON SYSTEMATICS EVOLUTION OF THE SOCIETY OF PROTOZOOLOGISTS. The Journal of protozoology, v. 27, n. 1, p. 37-58, 1980.
LYONS, R. E.; JOHNSON, A. M. Heat shock proteins of Toxoplasma gondii. Parasite immunology, v. 17, n. 7, p. 353-359, 1995.
MCALLISTER, Milton M. et al. An immunohistochemical method for detecting bradyzoite antigen (BAG5) in Toxoplasma gondii-infected tissues cross-reacts with a Neospora caninum bradyzoite antigen. The Journal of parasitology, v. 82, n. 2, p. 354-355, 1996.
MCAULEY, James et al. Early and longitudinal evaluations of treated infants and children and untreated historical patients with congenital toxoplasmosis: the Chicago Collaborative Treatment Trial. Clinical infectious diseases, v. 18, n. 1, p. 38-72, 1994.
NATH, M.; POKHARIA, S.; YADAV, R. Calix [4] arenes as Molecular Platforms in Magnetic Resonance Imagery. Coord. Chem. Rev, v. 215, p. 99-149, 2001.
PORTES, J. A. et al. Reduction of Toxoplasma gondii development due to inhibition of parasite antioxidant enzymes by a dinuclear iron (III) compound. Antimicrobial agents and chemotherapy, v. 59, n. 12, p. 7374-7386, 2015.
RAMÍREZ-MACÍAS, Inmaculada et al. Biological activity of three novel complexes with the ligand 5-methyl-1, 2, 4-triazolo [1, 5-a] pyrimidin-7 (4 H)-one against Leishmania spp. Journal of antimicrobial chemotherapy, v. 66, n. 4, p. 813-819, 2011.
SINGH, H. L.; SHARMA, M.; VARSHNEY, A. K. Studies on coordination compounds of organotin (IV) with schiff bases of amino acids. Sythesis and Reactivity in Inorganic and Matel-Organic Chemistry, v. 30, n. 3, p. 445-456, 2000.
SULLIVAN JR, William J.; SMITH, Aaron T.; JOYCE, Bradley R. Understanding mechanisms and the role of differentiation in pathogenesis of Toxoplasma gondii: a review. Memorias do Instituto Oswaldo Cruz, v. 104, n. 2, p. 155-161, 2009.
TENTER, Astrid M.; HECKEROTH, Anja R.; WEISS, Louis M. Toxoplasma gondii: from animals to humans. International journal for parasitology, v. 30, n. 12-13, p. 1217-1258, 2000.
