Therapeutic Targets on Toxoplasma gondii Parasite in Combatting Toxoplasmosis
Annual Research & Review in Biology,
Page 1-15
DOI:
10.9734/arrb/2019/v32i230081
Abstract
The status of toxoplasmosis management is challenged by drug intolerance, compromised efficacy and potential development of drug resistance. However, currently, there are very limited targets on T. gondii that serve as the site of action of current medications. This review aimed to explore more potential targets that are essential to parasite survival and are absent in humans. Many unexplored targets on T. gondii exist and their specificities to the parasite make them ideal drug targets. The present review had searched relevant English databases such as PubMed, Scopus, Google scholar and Science Direct, for relevant literature on the therapeutic target of T. gondii. Many of the enzyme systems in several pathways are essentially palatable as drug targets. Establishing compounds that can target these enzymes on T. gondii will greatly be beneficial in treating acute and chronic toxoplasmosis in humans.
Keywords:
- Toxoplasmosis
- T. gondii
- essential
- drug
- targets
- enzymes.
How to Cite
Abdullahi, S., Unyah, N., Nordin, N., Basir, R., Nasir, W., Alapid, A., Hassan, Y., Mustapha, T., & Majid, R. (2019). Therapeutic Targets on Toxoplasma gondii Parasite in Combatting Toxoplasmosis. Annual Research & Review in Biology, 32(2), 1-15. https://doi.org/10.9734/arrb/2019/v32i230081
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McFadden DC, Camps M, Boothroyd JC. Resistance as a tool in the study of old and new drug targets in Toxoplasma. Drug Resistance Updates. 2001;4(2):79-84.
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Meneceur P, Bouldouyre MA, Aubert D, Villena I, Menotti J, Sauvage V, Derouin F. In vitro susceptibility of various genotypic strains of Toxoplasma gondii to pyrime-thamine, sulfadiazine, and atovaquone. Antimicrobial Agents and Chemotherapy. 2008;52(4):1269-1277.
Müller J, Hemphill A. New approaches for the identification of drug targets in proto-zoan parasites. In International Review of Cell and Molecular Biology. Academic Press. 2013;301:359-401.
Lim DC, Cooke BM, Doerig C, Saeij JP. Toxoplasma and Plasmodium protein kinases: Roles in invasion and host cell remodeling. International Journal for Parasitology. 2012;42(1):21-32.
Wei F, Wang W, Liu Q. Protein kinases of Toxoplasma gondii: Functions and drug targets. Parasitology Research. 2013; 112(6):2121-2129.
Wang Y, Yin H. Research advances in microneme protein 3 of Toxoplasma gondii. Parasites & Vectors. 2015;8(1):384.
Peixoto L, Chen F, Harb OS, Davis PH, Beiting DP, Brownback CS, Roos DS. Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses. Cell Host & Microbe. 2010;8(2):208-218.
Ojo KK, Larson ET, Keyloun KR, Castaneda LJ, DeRocher AE, Inampudi KK, Napuli AJ. Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors. Nature Structural and Molecular Biology. 2010; 17(5):602.
Kato K, Sugi T, Iwanaga T. Roles of apicomplexan protein kinases at each life cycle stage. Parasitology International. 2012;61(2):224-234.
Morlon‐Guyot J, Berry L, Chen CT, Gubbels MJ, Lebrun M, Daher W. The Toxoplasma gondii calcium‐dependent protein kinase 7 is involved in early steps of parasite division and is crucial for parasite survival. Cellular Microbiology. 2014;16(1):95-114.
Doggett JS, Ojo KK, Fan E, Maly DJ, Van Voorhis WC. Bumped kinase inhibitor 1294 treats established Toxoplasma gondii infection. Antimicrobial agents and Chemo-therapy. 2014;58(6):3547-3549.
Moine E, Dimier-Poisson I, Enguehard-Gueiffier C, Logé C, Pénichon M, Moiré N, Gueiffier A. Development of new highly potent imidazo [1, 2-b] pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1. European Journal of Medicinal Chemistry. 2015;105: 80-105.
Zhang Z, Ojo KK, Johnson SM, Larson ET, He P, Geiger JA, Maly DJ. Benzoylbenzi-midazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1. Bioorganic & Medicinal Chemistry Letters. 2012;22(16):5264-5267.
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